Title of Invention	TRI-ARYL ACID DERIVATIVES AS PPAR RECEPTOR LIGANDS
Abstract	ABSTRACT 1N/PCT/2001/Q1473/CHE "Tri-arvl acid derivatives as PPAR receptor ligands" The invention relates to a triaryl acid derivatives of formula I and their pharmaceutical compositions as PPAR Hgand receptor binders. The PPAR ligand receptor binders of this invention are useful as agonists or antagonists of the PPAR receptor.

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Background of the invemion This invemion is directed to the use of iriaryl acid derivatives and their pharmaceutical compositions as PPAR ligand receptor binders. The PPAR ligand receptor binders of this invention are useful as agonists or antagonists of the PPAR receptor. Field of the Invention Peroxisome proliferator-activated receptors (PPAR) can be subdivided into three subtypes, namely: PPARct, PPAR5, and PPARy. These are encoded by different genes (Motojima, Cell Structure and Function, 18:267-277, 1993). Moreover, 2 isoforms of PPARy also exist, PPARyi and yj . These 2 proteins differ in their NH; -lerminal-30 amino acids and are the result of alternative promoter usage and differential mRNA splicing (Vidal-Puig, Jimenez, Linan, Lowell, Hamann, Hu, Spiegelman, Flier, Moller, J. Clin. Invest., 97:2553-2561, 1996). Biological processes modulated by PPAR are those modulated by receptors, or receptor combinations, which are responsive to the PPAR receptor Itgands described herein. These processes include, for example, plasma lipid transport and fatty acid catabolism, regulation of insulin sensitivity and blood glucose levels, which are involved in hypoglycemia/hyperinsulinism (resulting from, for example, abnormal pancreatic beta cell function, insulin secreting tumors and /or autoimmune hypoglycemia due to autoantibodies to insulin, the insulin receptor, or autoantibodies that are stimulatory to pancreatic beta cells), macrophage differentiation which lead to the formation of atherosclerotic plaques, inflammatory response, carcinogenesis, hyperplasia or adipocyte differentiation. Obesity is an excessive accumulation of adipose tissue. Recent work in this area indicates that PPARy plays a central role in the adipocyte gene expression and differentiation. Excess adipose tissue is associated with the development of serious medical conditions, for example, non-insulin-dependent diabetes melIitus(NIDDM), hypertension, coronary artery disease, hyperlipidemia and certain malignancies. The adipocyte may also influence glucose homeostasis through the production of tumor necrosis factor a (TNFa) and other molecules. Non-insulin-dependent diabetes mellitus (NIDDM), or Type 11 diabetes, is the more common form of diabetes, with 90-95% of hyperglycemic patients experiencing this form of the disease. In NIDDM there appears to be a reduction in the pancreatic g-cell mass, several distinct defects in insulin secretion or a decrease in tissue sensitivity to insulin. The symptoms of this form of diabetes include fatigue, frequent urination, thirst, blurred vision, frequent infections and slow healing of sores, diabetic nerve damage and renal disease. Resistance to ihe metabolic actions of insulin is one of the key features of non-insulin dependent diabeies (NIDDM). Insulin resistance is characterised by impaired uptake and utilization of eiucose in insulin-sensitive target organs, for example, adipocytes and skeletal muscle, and by impaired inhibition of hepatic glucose output. The functional insulin deficiency and the failure of insulin to supress hepatic" glucose output results in fasting hyperglycemia. Pancreatic P-cells compensate for the insulin resistance by secreting increased levels of insulin. However, the |3-celis are unable to maintain this high output of insulin, and, eventually, the glucose-induced insulin secretion falls, leading to the deterioration of glucose homeostasis and to the subsequent development of overt diabetes. Hyperinsulinemia is also linked to insulin resistance, hypertriglyceridaemia and increased plasma concentration of low density lipoproteins. The association of insulin resistance and hyperinsulinemia with these metabolic disorders has been temied "Syndrome X'^ and has been strongly linked to an increased risk of hypertension and coronary artery disease. Metformin is known in the art to be used in the treatment of diabetes in humans (US Patent No. 3,174,901). Metformin acts primarily to decrease liver glucose production. Troglitazone® is known to work primarily on enhancmg the ability of ^cletal muscle to respond to insulin and take up glucose, h is knovm that combination therapy comprising metfonnin and troglitazone can be used in the treatment of abnoimalities associated with diabetes (DDT 3:79-88, 1998). PPAR Y activators, in particular Troglitazone®, have been found to convert cancerous tissue to normal cells in liposareoma, a tumor of fat (PN AS 96:3951-3956,1999). Furthermore, it has been suggested that PPAR y activators may be usefiil in the treatment of breast and colon cancer (PNAS 95-.8806-88U, 1998, Nature Medicine4:1046-10S2,1998). Moreover, PPARy activators, for example Troglitazone®, have been implicated in the treatment of polycystic ovary syndrome (PCO). This is a syndrome in women that is characterized by chronic anovulation and hyperandrogenism. Women with this syndrome often have insulin resistance and an increased risk for the development of noninsulin-dependent diabetes melHtus. (Dunaif, Scott, Finegood, Quintana, Whitcomb, J. Clin. Endocrinol. Metab., 81:3299, 1996. Furthermore, PPARy activators have recently been discovered to increase the production of progesterone and inhibit steroidogenesis in granulosa cell cultures and therefore may be usefiil in the treatment of climacteric. (United States Patent 5,814,647 Urban et al. September 29, 1998; B. Lohrke et al. Journal of Edocrinology, 159,429-39, 1998). Climacteric is defined as the syndrome of endocrine, somatic and psychological changes occurring at the termination of the reproductive period in the female. Peroxisomes arc cellular organelles which play a role in controlling the redox potential and oxidative stress of cells by metabolizing a variet}' of substrates such as hydrogen peroxide. There are a number of disorders associated with oxidative stress. For example, inflammatory response to tissue injury, palhoeenesis of emphysema, ischemia-associated organ injury (shock), doxorubicin-induced cardiac injury, drug-induced hepaiotoxicity, atherosclerosis, and hyperoxic lung injuries, are each associated with the production of reactive oxygen species and a change in the reductive capacity of the ceil. Therefore, it is envisaged that PPARa activators, among other things, regulate the redox potential and oxidative stress in cel-is, would be effective in the treatment of these disorders (Poynter et al, J. Biol Chem. 273,32833-41, 1998). It has also been discovered that PPARa agonists inhibit NFKB-mediated transcription thereby modulating various inflammatory responses such as the inducible nitric oxide synthase (NOS) and cyciooxygenase-2 (COX-2) enzyme pathways (Pineda-Torra, 1. T al, 1999, Curr. Opinion in LipidoJogy, 10,151-9 ) and thus can be used in the therapeutic intervention of a wide variety of inflammatory diseases and other pathologies (Colville-Nash, et ai.. Journal of Immunology, 161, 978-84, 1998; Staels et al. Nature. 393, 790-3, 1998). Peroxisome proliferators activate PPAR , which in turn, acts as a transcription factor, and causes differentiation, cell growth and proliferation of peroxisomes. PPAR activators are also thought to play a role in hyperplasia and carcinogenesis as well as altering the enzymatic capability of animal cells, such as rodent cells, but these PPAR activators appear to have minimal negative effects in human ceils (Green, Biochem. Pharm. 43(3):393, 1992). Activation of PPAR results in the rapid increase of gamma glutamyl transpeptidase and catalase. PPARa is activated by a number of medium and long-chain fatty acids and is involved in stimulating ^-oxidation of fatty acids in tissues such as liver, heart, skeletal muscle, and brown adipose tissue (Isseman and Green, supra; Beck et al., Proc. R. Soc. Lond. 247:83-87, 1992; Gottlicher et al^ Proc. 'Natl. Acad. Sci. USA 89:4653-4657,1992). Pharmacological PPARa aaivators, for example fenofibrate, clofibrate, genfibrozil, and bezafjbrate, are also involved in substantial reduction in plasma triglycerides along with moderate reduction in LDU cholesterol, and they are used particularly for the treatment of hypertriglyceridemia, hyperlipidemia and obesity. PPARa is also known to be involved in inflammatory disorders. (Schoonjans, K., Cuirent Opionion in Lipidology, 8, 159-66,1997). The human nuclear receptor PPAR6 has been cloned from a human osteosarcoma ceil cDNA library and is fully described in A. Schmidt et al.. Molecular Endocrinology, 6:1634-1641 (1992), the contents of which are hereby incorporated herein by reference. It should be noted that PPAR5 is also referred to in the literature as PPARp and as NUC1, and each of these names refers to the same rector. For example, in A. Schmidt et al.. Molecular Endocrinology, 6: pp. 1634-1641, 1992, the receptor is referred to as NUC1. PPAR5 is observed in both embryo and adult tissues. This receptor has been reported to be involved in regulating the expression of some fat-specific genes, and plays a role in the adipogenic process (Amri. E. et al.. J. Biol. Chem. 270,2367-71, 1995). Atherosclerotic disease is known to be caused by a number of factors, for example, hvpertension, diabetes, low levels of high density Hpoproiein (HDU, and high levels of low density lipoprotein (LDL). in addition lo risk reduction via effects on plasma iipid concentrations and other risk factors, PPARct agonists exert direct alhemprotective effects (Frick, M. H.,ei al. 1997.. Circulation 96:2137-2143, de Faire, etal. 1997. Cardiovasc. Drugs Then 11 Suppl 1:257-63:257-263). It has recently been discovered thai PPAR5 agonists are useful in raising HDL levels and therefore useful in treating atherosclerotic diseases. (Leibowitz ei al.; WO/9728149). Atherosclerotic diseases include vascular disease, coronary hean disease, cerebrovascular disease and peripheral vessel disease. Coronary heart disease includes CHD death, myocardial infarction, and coronary revascularization. Cerebrovascular disease includes ischemic or hemorrhagic stroke and transient ischemic attacks. PPAR7 subtypes are involved in activating adipocyte differentiation, and are not involved in stimulating peroxisome proliferation in the liver. Activation of PPARf 's implicated in adipocyte differentiation through the activation of adipocyte-specific gene expression (Lehmann, Moore, Smith-Oliver, Wilkison, Willson, Kliewer. J. Biol. Chem., 270:12953-12956,1995). The DMA sequences for the PPARy receptors arc described in Eibrechi et aU BBRC 224;431-437 (1996). Although peroxisome proliferators, including fibrates and fatty acids, activate the transcriptional activity of PPAR's, only prost^landin J2 derivatives such as the arachidonic acid metabolite 15-deoxy-delta",14 -prostaglandin h (ISd-PGJj) have been identified as natural ligands specific for the PPARy subtype, which also binds thiazoiidinediones.This prostaglandin activates PPARy-dependent adipogenesis, but activates PPARa onlyathighcQncentrations(Forman,Tontono2,Cheti,Bnm,Spiegelman,Evans, Cell, 83:803-812, 1995; Kliewer, Lenhard, Wilson, Patel, Morris, Lehman, Cell, 83:813-819, 1995). This is further evidence that the PPAR family subtypes are distinct from one another in their pharmacological response to ligands. It has been suggested that compounds activating both PPARxt and PPARy should be potent hypotriglyceridemic drugs, which could be used in the treatment of dyslipidemia associated with atherosclerosis, non-insulin dependent diabetes meUitus,Syndrome X,. (Staels, B. et al., Cun. Pharm. Des., 3 (I), 1-14 (1997)) and familial combined hyperiipidemia (FCH). Syndrome X is the syndrome characterized by an initial insulin resistant stale, generating hyperinsulinaemia, dyslipidaemia and impaired glucose tolerance, which can progress to non-insutin dependent diabetes meliitus (Type 11 diabetes), characterized by hyperglycemia. FCH is characterized by hypercholesterolemia and hypertriglyceridemia within the same patient and family. The present invention is directed to a series of compounds that are useful in modulating PPAR receptors, as well as to a number of other pharmaceutical uses associated therewith. Summary of the Invention This invention provides new aromatic compounds and pharmaceutical compositions preoared therewith that are PPAR ligand receptor binders, and v^-hich are useful as agonists or antagonists of the PPAR receptors. The invention also includes the discovery of new uses for previously known compounds. The compounds for use according to the invention, including the new compounds of the presfent invention, are of Fonnula I fused arylheterocyclenyl, fiised arylheterocyclyl, heteroaryl, fused heteroarylcycloalkenyl, fbsed hetcroaiylcycloalkyl, fiised heteroarylheterocyclenyl, or fused hetero^^lheterocyclyl; E is a chemical bond or an ethylene group; a is 0-4; b is 0-4-, CIS 0-4; d is 0-5; e is 0-4; f is 0-6; g is 1-4; h is 1-4; Ri. Rs, Rs, Ri. Rq. and RH, are independently hydrogen, halogen, alky!, carboxyl. alkoxycarbonyl or aralkyi; R2. R^, R^ Rg, R]o and R^, are independently -(CHi)q-X; q is 0-3; X is hydrogen, halogen, alkyl, alkenyl, cycioalkyl, heterocyclyl, aryi. heteroaryl, ara.lky!, heieroaralkyl, hydroxy, alkoxy, aralkoxy, heteroaralkoxy, carboxyl, alkoxycarbonyl, leirazolyi, acyl, acylHNSOi-, - SR:,, Y'Y^- or Y^Y'^NCO-; Y and y^ are independently hydrogen, aikyi, aryl, aralkyl or heteroaralkyl, or one of Y and Y is hydrogen or afkyl and the other of Y and Y is acyl or aroyi; Y and Y^ are independently hydrogen, alkyl, aryi, aralkyl or heteroaralkyl; Z is RjiCbC-, RjiOC-, cyclo-imide, -CN, RajOaSHNCO-, R21O2SHH-, (R2i)2NCO-, RjiO- 2,4- thiazolidinedionyl, or letrazotyi; and Risand Kn are independently hydrogen, alkyl, aryl, cycioalkyl, or aralkyl; Rij, Rn, Ri9 and Ry are iadependently R23OC-, R32NHOC-, hydrogen, alkyl, aryl, heteroaryl, cyclodkyl, heterocyclyl, heteroaralkyl, or aralkyl; R]^ Ris, R16, Kit and R» are independently hydrogen, alkyl, aralkyl, carbonyl, or alkoxycarbonyl; orRu, and Retaken together with the carbon and nitrogen atoms through which they are linked form a 5 or 6-membered a22heterocyclyl group; or when a is 2-4, then vicinal R, radicals taken together with tiie carbon atoms to which the Ri radicals are linked form an ethylene group;or when b is 2-4, then vicinal R3 radicals taken together with the carbon atoms to which the R3 radicals are linked form an ethylene group; or when c is 2-4, then vicinal Rs radicals taken together with the carbon atoms to which the R5 radicals are linked form an ethylene group; or when d is 2-S, then vicinal R7 radicals taken together with the carbon atoms to which the Ri radicals are linked form an ethylene group; or when e is 2-4, then vicinal R* radicals taken together with the carbon atoms to which the R9 radicals are linked form an ethylene group; or when f is 2-6, then vicinal R| I radicals taken together with the carbon atoms to which the Rn radicals are linked form an ethylene group; and R:: is hydrogen, alkyl, aryl, heteroaryl, cycioalkyl, heterocyclyl, heteroaralkyl, or aralkyl; or a phamiaceiitically acceptable salt thereof, an N-oxide thereof, a hydrate thereof or a solvate thereof DETAILED DESCRIPTION OF THE INVENTION As employed above and throughout the disclosure, the foHowing terms, unless otherwise indicated, shall be understood to have the following meanings; Definitions In the present specification, the lerm "compounds for use according to the invention", and equivalent expressions, are meant to embrace compounds of general Formuia (I) as hereinbefore described, which expression includes the prodrugs, the phannaceutically acceptable salts, and the solvates, e.g. hydrates, where the context so permits. Similarly, reference to intermediates, whether or not they themselves are claimed, is meant to embrace their salts, and solvates, where the context so permits. For the sake of clarity, particular instances when the context so permits are sometimes indicated in the text, but these instances are purely illustrative and it is not intended to exclude other instances when the context so permits. "Prodrug" means a compound which is convertible in vivo by metabolic means (e.g. by hydrolysis) to a compound of Formula (I), including N-oxides thereof. For example an ester of a compound of Formula (I) containing a hydroxy group may be convertible by hydrolysis in vivo to the parent molecule. Alternatively an ester of a compound of Formula (I) containing a carboxy group may be convertible by hydrolysis in vivo to the parent molecule. "Patient" includes both human and other mammals. "Chemical bond" means a direct single bond between atoms. "Acyl" means an H-GO- or alkyl-CO- group wherein the alkyl group is as herein described. Preferred acyls contain a lower alkyl. Exemplary acyl groups include formyl, acetyl, propanoyi, 2-metfiylpropanoyl, butanoyl and palmitoyl. "Alkenyl" means an aliphatic hydrocarbon group containing a carbon-carbon double bond and which may be a straight or branched chain having about 2 to about 15 carbon atoms in the chain. Preferred alkenyl groups have 2 to about 12 carbon atoms in the chain and more preferably about 2 to about 4 carbon atoms in the chain. Branched means that one or more lower alkyl groups such as methyl, ethyl or propyl are attached to a linear alkenyl chain. "Lower alkenyl" means about 2 to about 4 carbon atoms in the chain, which may be straight or branched. The alkenyl group is optionally substituted by one or more halo groups. Exemplary alkenyl groups include ethenyl, propenyl, n-butenyl, /-butenyl, 3-methylbut-2-enyl. n-pentcnyl, heptenyl, octenyt and decenyl. "Alkoxy" means an aIkyI-0- group wherein the alkyl group is as herein described. Exemplary alkoxy groups include methoxy, ethoxy, n-propoxy, /-propoxy, n-butoxy and heptoxy. "Alkoxycarbonyl" means an aikyI-0-CO- group, wherein the alkyl group is as herein defined. Exemplary alkoxycarbonyl groups include m ethoxycarbonyI, ethoxycarbonyl, or t-butylo.-tycarbonyl. "Alkyl" means an aliphatic hydrocarbon group which may be a straight or branched chain having about \ to about 20 carbon atoms in the chain. Preferred alkyl groups have I to about 13 carbon atoms in the chain. Branched means thai one or more lower alkyl groups such as methyl, ethyl or propyl are attached to a linear alkyl chain- "Lower alky!" means that there are about I to about 4 carbon atoms in the chain, which may be straight or branched- The alkyl is optionally subsiitmed with one or more "alkyl group substituents" which may bethe same or difFereni. and include haio. carboxy, cycloalkyi, cycioalkenyl. heierocyclyl, heterocycienyl, aryl, alkoxy, alkoxycarbonyl. aralkoxycarbonyl, heteroaralkoxycarbonyi, Y VT^CO-, wherein Y and Y are independentJy hydrogen, alkyl, aryL aralkyl or heteroaralkyl, or Y and Y taken together with the nitrogen atom to which Y and Y~ are attached form heterocyclyl. Exemplary alkyl groups include methyl, trifluoromethyl. ethyl, n-propyl, /-propyl, n-butyl, l-buTyl, H-pentyl. and 3-penTyl. Preferably, the alkyl group subslituent is selected from acyl. halo, carboxy, carboxymethyl, methoxycarbonylethyl, benzyloxycarisonyimethyl, and pyridyimethyjoxycarbonylmethyl and alkoxycarbonyl. "Alkylsulfinyl" means an alkyl-SO- group wherein the alkyl group is as defined above. Preferred groups are those wherein the alkyl group is lower alkyl. " Alkylsulfonyl" means an alkyt-SCK-gnnip wherein the alkyl group is as defined above. Preferred groups are those wherein the alkyl group is lower alkyl. "Alkylthio" means an alkyl-S- group wherein the alk-yl group is as defined above. E.\empiary alkyllhio groups include methylthio, ethylthio, j-propylthio and hcptyithio. "Aralkoxy" means an aralkyl-O- group wherein the aralkyl group is as defined herein. Exemplary aralkoxy groups include benzyloxy and 1- and 2-naphthaleneme^oxy. "Aralkoxycarbonyl" means an aralkyl-0-CO group wherein the aralkyl group is as defined herein. An exemplary aralkoxycarbonyl group is benzyloxycarbonyl. "Aralkyl" means an aryl-alkyi- group wherein the aryl and alkyl groups are as defined herein. Preferred aralkyls contain a lower aJky! moiety. Exemplary aralkyl groups include benzyl, 2-phenethyl and naphthalenemethyl. "Aralkylsulfonyl" means an araikyl-SOr group wherein the aralkyl group is as defined herein. "Aralkylsulfinyl" means an aralkyl-SO- group wherein the aralkyl group is as defined herein. "Aralkyithio" means an aralkyl-S- group wherein the aralkyl group is as defined herein. An exemplary aralkyithio group is ben^Ithio. "Aroyl" means an aryl-CO- group wherein the aiyl group is as defined herein. Exemplary aroyl groups include benzoyl and 1- and 2-naphthoyl. "Aryl" means an aromatic monocyclic or multicyclic ring system of about 6 to about 14 carbon atoms, preferably of about 6 to about 10 carbon atoms. The ao"! is optionally substituted with one or more "Vins system substttuents" which may be the same or different, and arc as defined herein. Exemplary aryl groups include phenyl, naphfhyl. substituted phenyl, and substituted naphthyl. ■'Aryldiazo" means an aryl-diazo- group wherein the aryi and diazo groups are as defined herein. "Fused arylcycloalkenyl" means a fused aryl and cycloalkenyl as defined herein. Preferred fused arylcycioalkenyls are those wherein the ary! thereof is phenyl and the cycloalkenyl consists of about 5 to about 6 ring atoms. A fused arylcycioalkenyi group may be bonded to the rest of the compound through any atom of the fused system capable of such bondage. The fused aryicycloalkenyl may be optionally substituted by one or more ring system substituents, wherein the "ring system substituem" is as defined herein. Exemplary fused arylcycloalkenyl groups include 1,2-dihydronaphthyienyi; indenyl; 1,4-naphthoquinonyi, and the like. "Fused arylcycloalkyl" means a fused aryl and cycloalkyl as defined herein. Preferred fused arylcycloalkyls are those wherein the aryl thereof is phenyl and the cycloalkyl consists of about 5 to about 6 ring atoms. A fused arylcycloalkyl group may be bonded to the rest of the compound through any atom of the fused system capable of such bonding. The fused arylcycloalkyl may be optionally substituted by one or more ring system substituents, wherein the "ring system substituent" is as defined herein. Exemplary fused arylcycloalkyl and substituted fused arylcycloalkyl groups include 1,2,3,4-tetrahydronaphthyl; 1,4-dimethyl-2,3-dihydronaphthyl; 2,3-dihydro-1,4-naphthoquinonyl, a-tetralonyl, p-tetralony] and the like. "Fused arylheterocyclenyl" means a fused aryl and heterocyclenyl wherein the aryl and heterocyclenyl groups are as defmed herein. Preferred fused arylheterocyclenyl groups are those wherein the aryl thereof is phenyl and the heterocyclenyl consists of about 5 to about 6 ring atoms. A f\ised arylheterocyclenyl group may be bonded to the rest of the compound through any atom of the fused system capable of such bonding. The designation of aza, oxa orthiaas a prefix before the heterocyclenyl portion of the fused arylheterocyclenyl means that a nitrogen, oxygen or sulfur atom respectively, is present as a ring atom. The fused arylheterocyclenyl may be optionally substituted by one or more ring system substituents, wherein the "ring system substituent" is as defined herein. The nitrogen atom of a fused arylheterocyclenyl may be a basic nitrogen atom. The nitrogen or sulphur atom of the heterocyclenyl portion of the fused arylheterocyclenyl is also optionally oxidized to the corresponding N-oxide, S-oxide or S,S-dioxide. Exemplary {used arylheterocyclenyl and substituted fused arylheterocyclenyl groups include 3H-indolinyl, 2(IH)quinolinonyl, 4-oxo-l,4-dihydroquinoIinyI, 2H-]-oxoisoquinolyl, 1,2-dihydroquinoiinyl, (2H)quinolinyl N-oxide, 3,4-dihydroquinoliny!, 1,2-dihydroisoquinolinyl, 3,4-dihydroi5oquinolinyI, chromonyl, 3,4-dihydroisoquincxalinyl, 4-(3H)quina2olinonyl, 4H-chromen-2yl, and the like. Preferably, 2(1 H)quinolinonyl, 1,2-dihydroquinolinyl, (2H)quinolinyl N-oxide, or 4-C3H)quinazolinonyl. "Fused arylheterocyclyl" means a fused aryl and heterocyclyl wherein the aryl and heterocyclyl groups are as defined herein. Preferred fused ary\heterocyclyls are those wherein the aryl thereof is phenyl and the heterocyclyl consists of about 5 to about 6 ring atoms. A fused arylheterocyclyl may be bonded to the rest of the compound through any atom of the fused system capable of such bonding. The designation of aza, oxa or thia as a prefix before the heterocyclyl portion of the fused arylheterocyclyl means that a niirogen, oxygen or sulphur atom respectively is present as a ring atom. The fused aryiheierocyclyl group may be optionally substituted by one or more ring system substituents, wherein the "^ring system substiiueni'" is as defined herein. Tlie nitrogen atom of a fused aryiheierocvciyi may be a basic nitrogen atom. The nitrogen or sulphur atom of the heierocyclyl portion of the fiised arylheterocyclyl is also optionally oxidized to the corresponding N-oxide, S-oxide or S,S-dioxide. Exemplary fused arylheterocyclyl and substituted fused arylheterocyclyl groups include indolinyl, o-benzoic sulfimidyl, 4-chromanoiiyl, oxindole, 1,23,4-tetTahydroisoquinoiinyI, 1,2,3,4-tetrahydroquinolinyl, IH-2,3-dihydroisoindoi-2-yl, 2,3-dihydroben2[fjisoindol-2-yl, 1,2,3,4-tetrahydroben2[g]isoquinolin-2-yl, chromanyl, isochromanonyl, 23-dihydrochromonyl, l,4-ben2odioxan, 1,2,3,4-tetrahydroquinoxalinyi, andthe like. Preferably, 1,2,3,4-letrahydroisoquinoiinyl, 1,2,3,4-tetrahydroquinoxalinyl, and 1,2,3,4-tetrahydroquinoiinyi. "Aryloxy" means an aryl-O- group wherein the aryl group is as defined herein. Exemplary groups include phenoxy and 2-naphthyIoxy. "Aryloxycarbonyl" means an aryl-O-CO- group wherein the aiyl group is as defined herein. Exemplary aryloxycail>onyl groups include phenoxycarbonyl and naphthoxycarbonyl. "Arylsulfonyl" means an aryl-SOi- group wherein the aryl group is as defined herein. "Arylsulfinyl" means an aryl-SO- group wherein the aryl group is as defined herein. "Aiyllhio" means an aryl-S- group wherein the aryl group is as defined herein. Exemplary arylthio groups include phenyithio and naphthylthio. "Carbamoyl" is an NH2-CO- group. "Carbox/" means a HO(0)C- (carboxylic acid) group. "Compounds of the invention," and equivalent expressions, are meant to embrace compounds of general Formula (1) as hereinbefore described, which expression includes the prodrugs, the pharmaceutically acceptable salts, and the solvates, e.g. hydrates, where the context so permits. Similarly, reference to intermediates, whether or not they themselves are claimed, is meant to embrace their salts, and solvates, where the context so peraiits. For the sake of clarity, particular instances when the context so permits are sometimes indicated in the text, but these instances are purely illustrative and it is not intended to exclude other instances when the context so permits. "Cycloaikoxy" means an cycloalkyl-O- group wherein the cycloalkyl group is as defined herein. Exemplary cycloaikoxy groups include cyclopentyloxy and cyclohexyioxy. "Cycloalkenyl" means a non-aromatic mono- or multicyclic ring system of about 3 to about 10 carbon atoms, preferably of about 5 to about 10 carbon atoms, and which contains at least one carbon-carbon double bond. Preferred ring sizes of rings of the ring system include about 5 to about 6 ring atoms. The cycloalkenyl is optionally substituted with one or more "Ving system substituents" which may be the same or different, and are as defined herein. Exemplary monocyclic cycloalkenyl include cyclopentenyl, cyclohexenyL cycioheptenyi, and the like. An exemplary muiticyciic cvcloalkenv! is norbomylenyl. "CycioalkyI" means a non-aromatic mono- or muliicyclic ring system of about 3 to about 10 carbon aioms. preferably of abom,5 to about 10 carbon atoms. Preferred ring sizes of rings of the riilg system include about 5 to about 6 ring atoms. TTie cycloalkyi is optionally substituted with one or more "ring system subslituents"' which may be the same or different, and are as defined herein. Exemplary monocyclic cycloalkyi include cyclopentyi. cyclohexyl, cycioheptyL and the like. E.xemplary muiticyciic cycloalkyi include l-decalin. norbomyl, adamant-(l- or 2-)yl, and the like. "Cycloalkyiene" means a bivalent, saturated carbocyclic group having about 3 to about 6 carbon atoms. Preferred cycloalkyiene groups include 1,1-, 1,2-, 1,3-, and 1,4- cis ortrans-cyclohexylene; and 1,1-, 1,2-, and 1,3-cyclopeniylene. "Cyclo-imide" means a compound of formulae The cyclo-imide moiety may be attached to the parent molecule through either a carbon atom or nitrogen atom' of the carbamoyl moiety. An exemplary imide group is N-phthalimide. "Diazo" means a bivalent -N=N- radical. "Halo" means fluoro, chloro, bromo, or iodo. Preferred are fluoro, chloro and bromo, more preferably fluoro and chloro. -Heteroaralkyr means a heteroaryl-alkyl- group wherein the heteroaryl and alkyl groups are as defined herein. Preferred heteroaralkyls contain a lower alkyl moiety. Exemplary heteroaralkyl groups include ihienylmethyl, pyridyimethyl, imidazolylniethyl and pyrazinylmethyl. "Heteroaralkylthio" means a heteroaralkyl-S- group wherein the heteroaralkyl group is as defined herein. An exemplary heteroaralkylthio group is 3-pyridinepropanthiol. "Heteroaralkoxy" means an heteroaraikyl-O- group wherein the heteroaralkyl group is as defined herein. An exemplary heteroaralkoxy group is 4-pyridylmethyloxy. "Heteroaroyr means an means an hetcroaryl-CO- group wherein the heteroaryl group is as defined herein. E-xemplary heteroaryl groups include thiophenoyl. nicotinoyi, pyrroi-2-ylcarbonyi and 1-and 2-naphlhoyl and pyridinoyi. "Heteroarvldiazo" means an heieroap,'l-diazo- group wherein the heteroaryl and diazo groups are as defined herein. "Heteroaryl" means an aromatic monocyclic or muUicydic ring system of about 5 to about 14 carbon atoms, preferably about 5 to about 10 carbon atoms, in which at least one of the carbon atoms'in the ring system is replaced by a hetero atom. i.e.. other than carbon, for example nitrogen, oxygen or sulfur. Preferred ring sizes of rings of the ring system include about 5 to about 6 ring atoms. The heteroaryl ring is optionally substituted by one or more "ring system substituents" which may be the same or different, and are as defined herein. The designation of aza, oxa or thia as a prefix before the heteroaryl means that a nitrogen, oxygen or sulfur atom is present, respectively, as a ring atom. A nitrogen atom of an heteroaryl may be a basic nitrogen atom and also may be optionally oxidized to the corresponding N-oxide. Exemplary heteroaryl and substituted heteroaryl groups include pyrazinyl, thienyl, isothiazolyl, oxazoiyi, pyrazolyl, cinnolinyl, pteridinyl, benzofuryl, furazanyi, pyrrolyl, 1^,4-oxadiazolyl, benzoxazole, 1^,4-thiadiazolyl, pyridazinyl, indazolyl, quinoxalinyl, phthalazinyl, imidazo[l,2-a]pyridine, imidazo[2,I-b]thia2olyt, benzofurazanyl, azaindolyl, benzimidazolyl, benzothienyl, thienopyridyl, thienopyrimidyl, pyrrolopyridyl, imidazopyridyl, naphthyridinyl, benzoazaindole, 1,2,4-triazinyl, benzothiazolyl, furyl, imidazolyl, indolyl, isoindolyl, Indolizinyl, isoxazolyl, isoquinolinyl, isothiazolyl, oxadiazolyl, pyrazinyl, pyridazinyl, pyrazolyl, pyridyl, pyrimidinyi, pyrrolyl, quinazoiinyl, quinolinyl, l,3,4-thiadia2oIyl, thiazolyl, thienyl and triazolyl. Preferred heteroaryl and substituted heteroaryl groups include quinolinyl, indazolyl, indolyl, quinazoiinyl, pyridyl, pyrimidinyi, furyl, benzothiazolyl, benzoxazole, benzofuryl, quinoxalinyl, benzimidazolyl, 1,2,4-oxadtazolyl, benzothienyl, and isoquinolinyl. "Fused heteroarylcycloalkenyl" means a fused heteroaryl and cycloalkenyl wherein the heteroaryl and cycloalkenyl groups are as defined herein. Preferred fused heteroarylcycloalkenyls are those wherein the heteroaryl thereof is phenyl and the cycloalkenyl consists of about 5 to about 6 ring atoms. A fused heteroarylcycloalkenyl may be bonded to the rest of the compound through any atom of the fijsed system capable of such bonding. The designation of aza, oxa or thia as a prefix before the heteroaryl portion of the fused heteroarylcycloalkenyl means that a nitrogen, oxygen or sulfur atom is present, respectively, as a ring atom. The fused heteroarylcycloalkenyl may be optionally substituted by one or more ring system substituents, wherein the "ring system substituent" is as defined herein. The nitrogen atom of a fused heteroarylcycloalkenyl may be a basic nitrogen atom. The nitrogen atom of the heteroaryl portion of the fused heteroarylcycloalkenyl may also be optionally oxidized to the corresponding N-oxide. Exemplary fused heteroarylcycloalkenyl groups include 5,6-dihydroquinolyl; 5,6-dihydroisoquinQlyl-, 5,6-dihydroquinoxalinyl; 5,6-dihydroquinazoUnyl; 4,5-dihydro-l H-benzimidazolyl; 4,5-dihydrobenzoxazolyl; 1.4-naphthoquinolyl, and the like. "Fused heteroarylcycloalkyl" means a fused heteroaryl and cycloalkyl wherein the heterary! and cycioalkyl groups are as defined herein. Preferred fused heleroarylcycioalkyls are those wherein the heieroaryl thereof consists of about 5 to about 6 ring atoms and the cycloalkyl consists of about 5 to about 6 ring atoms. A fused heteroarylcycloalkyl may be bonded to the rest of the compoun through any atom of the fused system capable of such bonding. The designation ofaza, oxa or thia as a prefix before the heteroaryl portion of the fused heteroarylcycloalkyl means that a nitrogen, oxygen or sulfur atom is present respectively as a ring atom. The fused heteroarylcycloalkyl may be optionally substituted by one or more ring system substituents, wherein the "ring system substituent" is as defined herein. The nitrogen atom of a fused heteroarylcycloalkyl may be a basic nitrogen atom. The nitrogen atom of the heteroaryl portion of the fused heteroarylcycloalkyl may also be optionally oxidized to the corresponding N-oxide. Exemplary fijsed heteroarylcycloalkyl include 5,6,7,8-tetrahydroquinolinyl; 5,6,7,ft-tetrahydroisoquinolyl; 5,6,7,8-ietrahydroquinoxalinyl; 5,6,7,S-tetrahydroquinazolyl; 4,5,6,7-letrahydro-1 H-benzimidazolyl; 4,5,6,7-tetrahydrobenzoxazoiyl; lH-4-oxa-l,5-diazanaphthalen-2-oniy; l,3-dihydroimidizole-[4,5]-pyridin-2-only; 2.3-dihydri>-l,4-dinaphthoquinonyl and the like, preferably, 5,6,7,8-tetrahydroquinoliryl or 5,6,7,8-tetrahydroisoquinoIyl, "Fused heteroarylheterocyclenyl" means a fused heteroaryl and heterocyclenyl wherein the heteraryl and heterocyclenyl groups are as defined herein. Preferred fused heteroarylheterocyclenyls are those wherein the heteroaryl thereof consists of about 5 to about 6 ring atoms and the heterocyclenyl consists of about 5 to about 6 ring atoms. A fused heteroarylheterocyclenyl may be bonded to the rest of the compound through any atom of the fused system capable of such bonding. The designation ofaza, oxa or thia as a prefix before the heteroaryl or heterocyclenyl portion of the fused heteroarylheterocyclenyl means that a nitrogen, oxygen or sulfur atom is present respectively as a ring atom. The fused heteroarylheterocyclenyl may be optionally substituted by one or more ring system substituent, wherein the "ring system substituent" is as defined herein. The nitrogen atom of a fused heteroarylazaheterocyclenyl may be a basic nitrogen atom. The nitrogen or sulphur atom of the heteroaryl or heterocyclenyl portion of the fused heteroarylheterocyclenyl may also be optionally oxidized to the corresponding N-oxide, S-oxide or S,S-dioxide. Exemplary fused heteroarylheterocyclenyl groups include 7,8-dihydro[l,7]naphthyridinyl; l,2-dihydro[2,7]naphthyridinyl; 6,7-dihydro-3H-imidazo[4,5-c]pyridyl; l,2-dihydro-l,5-naphthyridinyl; l,2-dihydro-l,6-naphthyridinyl; l,2-dihydro-I,7-naphthyridinyi; 1,2-dihydro-1,8-naphthyridinyI; 1,2-dihydro-2,6-naphthyridinyI, and the like. "Fused heteroarylheterocyclyl" means a fused heteroaryl and heterocyclyl wherein the heteroaryl and heterocyclyl groups are as defined herein. Preferred fused heteroaryl heterocyciyIs are those wherein the heteroaryl thereof consists of about 5 to about 6 ring atoms and the heterocyclyl consists of about 5 to about 6 ring atoms. A fused heteroarylheterocyclyl may be bonded to the rest of the compound through any atom of the fused system capable of such bonding. The designation ofaza, oxa or thia as a prefix before the heteroaryl or heterocyclyl portion of the fused heteroarylheterocyclyl means that a nitrogen, Qxyget^ or sulfur atom ts present respectively as a ring atom. The fused heteroarylheterocyclyl may be optionaJly substituted by one or more ring system subsiituent, wherein the "ring system substituent" is as deilned herein. The nitrogen atonn of a fused heteroaryihelerocyclyl may be a basic nitrogen atom. The nitrogen or sulphur atom of the heteroaryl or heierocyclyl portion of the fused heteroarylheterocyclyi may also be optionally oxidized to the corresponding N-oxide, S-oxide or S,S-dioxide. Exemplary fused • heieroarylheterocyclyl groups include 2J-dihydro-lH pyrrol[3,4-b]quinoIin-2-yl; i;i3,4-tetrahydrobenz lb][l,71i\aphUiyndin-2-yl; l,2,3,4-teirahydroben2 (;b][I,6]naphthyridin-2-yl; l,23,4-tetrahydro-9H-pyrido[3,4-b]indol-2yl; I,2,3,4-tetrahydro-9H-pyrido[43-b]indol-2yl, 2,3,-d^hydro-IH-pyrrolo[3,4-b]indol-2-yl; IH-2,3,4,5-letrahydroa2epino[3,4-b]indoI-2-yi; lH-2,3,4,5-tetrahydroa2epino[4,3-b]indoi-3-yl; lH-2,3,4,5-tetrahydrDa2epino[4,5-b]indo(-2yi, 5,6,7,&-tetrahydrotl,7Jnapthyridinyi; 1^3^ tetrhydro[2,7]naphthyridyi;23-dihydro[I,4]dioxino[2,3-b]pyridyl;2,3-dihydro[l,4]dioxino[2,3-b]pryidyl;3,4-dihydro-2H-l-oxa[4,6]dia2anaphthalenyl;4,5,6,7-tetrahydro-3H-iniidazo[4^-c]pyridyI; 6,7-dihydro[5,81dia2anaphthalenyl; l,2,3,4-tetrahydro[l,5] naptiiyridinyl; 1^3,4-tetrahydro[ 1,6]napthyridinyi; I^3,4-letrahydro[i ,73napthyridtnyl; 1 ^,3.4-tetrahydro[\,8]napthyridinyi; l23 "Heteroarylsulfonyr means an heteroaryi-SOr group wherein the heteroaryl group is as defined herein. An examplary heterarylsulfonyl groups is 3-pyridinepropansulfonyl. "Heteroarylsulfinyi" means an heteroaryl -SO- group wherein the heteroaryl group is as defined herein. "Heteroarylthio" means an heteroaryl -S- group wherein the heteroaryl group is as defined herein. Exemplary heteroaryl ihio groups include pyridylthio and quinolinyllhio. "Heterocyclenyr means a non-aromatic monocyclic or multicyclic hydrocarbon ring system of about 3 to about 10 carbon atoms, preferably about 5 to about 10 carbon atoms, in which at least one or more of the cariwn atoms in the ring system is replaced by a hetero atom, for example a nitrogen, oxygen or suifiir atom, and which contains at least one carbon-carbon double bond or carbon-nitrogen double bond. Preferred ring sizes of rings of the ring system include about 5 to about 6 ring atoms. The designation of aza, oxa or thia as a prefix before the heterocyclenyl means that a nitrogen, oxygen or sulfur atom is present respectively as a ring atom. The heterocyclenyl may be optionally substituted by one or more ring system substituents, wherein the "ring system substituent" is as defined herein. The nitrogen atom of an heterocyclenyl may be a basic nitrogen atom. The nitrogen or sulphur atom of the heterocyclenyl is also optionally oxidized to the corresponding N-oxide, S-oxide or S,S-dioxide. Exemplary monocyclic azaheterocyclenyl and substituted monocyclic azaheterocyclenyl groups include 1,2,3,4-tetrahydrohydropyridine, 1,2-dihydropyridyl, 1,4-dihydropyridyl, 133,6-tetrahydropyridine, 4{3H)pyrimidone, 1,4,5,6-teirahydropyrimidine, 2-pyrrolinyl,3-pyrroIinyl, 2-imidazolinyl,2-pyrazoiinyl, and the like. Exemplary oxaheterocycienyl groups include 3,4-dihydro-2/f-pyran, dihydrofiiryl, and fluorodihydrofuryi An exemplary multicyclic oxaheterocycienyl group is 7-oxabicyc}o[2.2.1]heptenyl. Exemplary monocyclic thiaheterocycleny rings include dihvdrothioohenvl and dihvdrothiopyranyl. "Heierocycly!" means a non-aromatic saiuraJed monocycitc or tnutticyclicrina system of abom3 10 about 10 carbon atoms, preferably about 5 to about 10 carbon atoms, in which at ieasi one of the carbon atoms in the ring system is replaced by a heiero atom, for example nitrogen, oxygen or sulfur. Preferred ring sizes of rings of the ring system include about 5 to about 6 ring atoms. The desisnation of aza, dxa or thia as a prefix before the Ueterocyclyl means that a nitrogen, oxygen or sulfur atom is presenl respectively as a ring atom. The heierocyclyl may be optionally substituted by one or more "rine system substituenis" which may be the same or different, and are as defined herein. The nitrogen atom of an heierocyclyl may be a basic nitrogen atom. The nitrogen or sulphur atom of the heierocyclyl is also optionally oxidized to the corresponding N-oxide. S-oxide or S,S-dioxide. Exemplarv monocyclic heierocyclyl rings include piperidyl, pyrrolidinyl, piperazinyi, morphoiinyL thicMnorpholrnyl, thiazolidinyl, 1^-dioxolanyl, 1,4-dioxany!, tetrahydrofiiryl, letrahydrothiophenyl. tetrahydrothiopyranyi, and the like. Exemplary mullicyclic heierocyclyl rings include 1.4 diazabicycIo-[2,2-2]octane and 1,2-cyclohexanedicarboxylic acid anhydride. "Ring system substituent" includes hydrogen, alkyl, cycloalkyi, heierocyclyl, aryl, beteroaryi, aralkyl, heteroaraikyi, hydroxy, alkoxy, aryloxy, aralkoxy, acyi, aroyi, halo, nhro, cyano, carboxy, alkojcycarbonyl, aryioxycarbonyl, aralkoxycarbonyl, alkyUuIfonyl, arylsulfonyl, heteroarylsulfonyi, alkylsulfinyl, arylsulfmyl, heteroarylsulfmyl, alkyllhio, arylthio, heteroarylthio, aralkylthio, heleroaralkylthio, fiised cycloalkyi, fused cycloalkenyl, fused heierocyclyl, fused hetcrocyclenyl, arylazo, heteroarylazo, R'R'^I-, R'R'*NCO-, R^OjCN-, and R'R'^S02- wherein R' and R*" are independently hydrogen, alkyl, aryl, aralkyl or heteroaraikyi, or one of R* and R" is hydrogen or alkyl and the other of R" and R** is aroyl or hettroaroyl. R' and R* are independently hydrogen, alkyl, aryi, beteroaryi, cycloalkyi, cycloalkenyl, heterocyclyl, hetcrocyclenyl, aralkyl or heteroaraikyi. Where the ring is cycloalkyi, cycloalkenyl, heterocyclyl or heterocyclenyl, the ring system substituent may also include methylene (H2C=), 0X0 (0=), Ihioxo (S=), on carbon aiom(s) diereof. Preferably, the ring substituents are selected from 0X0 (0=), (lower) alkyl, aryl, alkoxy, aralkoxy, halo, trifluoromethyl, carboxy. alkoxycarbonyl, optionally substituted phenyl, optionally substituted benzyloxy, optionally substituted cyclohexyl, optionally substituted cyclobutyl, optionally substituted heteroaiyl, and R'OiCN-, whensin R* is cycloalkyi. "Tetrazolyl" means a group of formula wherein the hydrogen atom thereof is optionally replaced by alkyl, carboxyalkyi or alkoxycarbonylalkyl. "PPAR ligand receptor binder" means a ligand which binds to the PPAR receptor. PPAR iigand receptor binders of this invention are useful as agonists or ajttagonists of the PPAR-CL, PPAR-5, or PPAR-"C receptor. The term "pharmacemically acceptable sail" refers to a relatively non-toxic, inorganic or organic acid addition salt of a compound of the present invention. A salt can be prepared ;n siiu during the final isolation and purification of a compound or by separately reacting the purified compound in its free base form with a suitable organic or inorganic acid and isolating the salt thus formed. Representative salts include the hydrobromide, hydrochloride, sulfate, bisulfate, phosphate, nitrate, acetate, oxalate, valerate, oieate, palmitate, siearate, laurate, borate, benzoate, lactate, phosphate, tosylate, citrate, maleate, fumarate, succinate, tartrate, naphthyiate, mesylate, glucoheptonate. lactiobionate, laurylsulphonate salts, and the like. (See, for example S. M. Berge, et al., "Pharmaceutical Salts." J. Pharm. Sci.. 66: 1-19, 1977, the contents of which are hereby incorporated herein by reference.) "Treating" means the partial or complete relieving or preventing of one or more physiological or biochemical parameters associated with PPAR activity. The term "modulate" refers to the ability of a compound to either directly {by binding to the receptor as a ligand) or indirectly (as a precursor for a ligand or an inducer which promotes production of a ligand from a precursor) induce expression of gcne(s) maintained under hormone control, or to repress expression of gene (s) maintained under such control. The term "obesity" refers generally to individuals who are at least about 20-30% over the average weight for the person's age, sex and height. Technically, "obese" is defined, for males, as individuals whose body mass index is greater than 27J kg/m'. Those skilled in the art readily recognize that the invention method is not limited to those who fall within the above criteria. Indeed, tiie invention method can also be advantageously practiced by individuals who fall outside of these traditional criteria, for example by those who are prone to obesity. The phrase "amount effective to lower blood glucose levels" refers to levels of a compound sufHcient to provide circulating concentrations high enough to accomplish the desired effect. Such a concentration typically falls in the range of about 1 OnM up to 2jiM, with concentrations in the range of about 10Onm up to about SOOnM being preferred. The phrase "amtmnt effective to lower triclyceride levels" refers to levels of a compound sufficient to provide circulating concentrations high enough to accomplish the desired effect. Such a concentration typically falls in the range of about lOnM up to 2[iM; with concentrations in the range of about i OOnm up to about SOOnM being preferred. Preferred Embodiments Preferred embodiments according to the invention includes the use of compounds of Formula 1 (and their phannaceutical compositions) as binders for PPAR receptors. More particularfy, the use of compounds of Formuia I thar bind to the PPAR-a receptor, compounds of Formula I that bind to the PPAR-S receptor, compounds of Fonruia I that bind to the PPAR-y receptor, compounds of Formula I that bind to the PPAR-a and the PPAR-y receptor, compounds of Formula 1 that fajnd to the PPAR-a and the PPAR-5 receptor, compounds of Formula I that bind to the PPAR-y and the PPAR-5 receptor, compounds of Formuia I that act as PPAR receptor agonists, compounds of Formula I that act as PPAR-a receptor agonists, compounds of Formula I that act as PPAR-5 receptor agonists^ compounds of Formuia I that act as PPAR-y receptor agonists, compounds of Formula I that act as both PPAR-a and PPAR-y receptor agonists, compounds of Formuia I that act as both PPAR-a and PPAR-& receptor ;^onists, compounds of Formuia I that act as botii PPAR-y and PPAR-5 receptor agonists, compounds of Formula I that act as both PPAR-a receptor antagonists and PPAR-y recepttH* agonists, compounds of Formula I that act as both PPAR-a receptor antagonists and PPAR-5 receptor agonists, compounds of Formula I and act as both PPAR-y receptor antagonists and PPAR-5 receptor agonists, cOTnpounds of Formula I that act as both PPAR-a receptor agonists and PPAR-y receptor antagonists, compounds of Formuia i that act as both PPAR-a receptor agonists and PPAR-6 receptor antagonists, compounds of Fonnula I that act as both PPAR-y receptor agonists and PPAR-5 rec^tor antagotiists, compounds of Formula I that act as PPAR receptor antagonists, compounds of Formula 1 that act as PPAR-a receptor antagonists, compounds of Formula I that act as PPAR-5 receptor antagonists, compounds of Formula I that act as PPAR-y receptor antagonists, compounds of Formula I that act as both PPAR-a and PPAR-y receptor antagonists, compounds of Formula 1 that act as both PPAR-a and PPAR-6 receptor antagonists, and compounds of Formuia I that act as both PPAR-y and PPAR-5 receptor antagonists. An embodiment according to the invention is directed to treating a patient suffering from a physiological disorder capable of being modulated by a compound of Formula I having PPAR ligand binding activity, comprising adminisiering lo the patient a phannaceutically effective amount of the compound, or a phannaceutically acceptable salt thereof. Physiological disorders capable of being so modulated include, for example, cell differentiation lo produce lipid accumulating cells, regulation of insulin sensitivity and blood glucose levels, which are involved in hypoglycemia/hyperinsulinism (resulting from, for example, abnormal pancreatic beta cell function, insulin secreting tumors and /or autoimmune hypoglycemia due to autoantibodies to insulin, autoantibodies to the insulin receptor, or autoantibodies thai are stimulatory to pancreatic beta cells), macrophage differentiation which leads to the formation of atherosclerotic plaques, inflammatory response, carcinogenesis, hyperplasia, adipocyte gene expression, adipocyte differentiation, reduction in the pancreatic P-cell mass, insulin seci^tion, tissue sensitivity to insulin, liposarcoma cell growth, chronic anovulation, hyperandrogenism, progesterone production, steroidogenesis, redox potential and oxidative stress in cells, nitric oxide synthase (NOS) production, increased gamma glutamyl transpeptidase, catalase, plasma triglycerides, HDL and LDL cholesterol levels and the [ike. Another embodiment according to the invention is directed to a method of treating a disease state in a patient with a phannaceutically effective amount of a compound of Formula I, or a phannaceutically acceptable salt thereof, wherein the disease is associated with a physiological detrimental blood level of insulin, glucose, free fatty acids (FFA), or triclycerides- An embodiment according to the invention is directed to treating a patient suffering fr^om a physiological disonler associated with physiologically detrimental levels of triclycerides in the blood, by administering to the patient a pharmaceutically effective amount of the compound, or of a pharmaceuticaliy acceptable salt thereof. An embodiment according to the invention is the use of compounds of Fonnula I and their phannaceutical compositions as anti-diabetic, anti-lipidemic, anti-hypertensive or anti-arteriosclerotic agents, or in the treatment of obesity. Another embodiment according to the invention is directed to a method of treating hyperglycemia in a patient, by administering to the patient a pharmaceutically effective amount lo lower Wood glucose levelsofacompoundof Formula!, or a pharmaceutically acceptable salt thereof. Preferably, the form of hypei^lycemia treated in accordance with this invention is Type II diabetes. Another embodiment according to the invention is directed to a method of reducing triglyceride levels in a patient, comprising administering to the patient a therapeutically effective amount (to lower triglyceride levels) of a compound of Formula I, or a pharmaceutically acceptable salt thereof. Another embodiment according to the invention is directed to a method of treating hyperinsulinism in a patient, comprising administering to the patient a therapeutically effective amount of a compound of Formula I. or a phannaceutically acceptable salt thereof. Another embodrment according to the invention is directed to a method of treating insulin resistance in a patient, comprising administering to the patient a therapeutically effective amount of a compound of Formula I, or a pharmaceutical ly acceptable salt thereof. Another embodiment according to the invention is directed to a method of treating cardiovascular disease, such as atherosclerosis in a patient, comprising administering to the patient a therapeutically effective amount of a compound of Formula I, or a pharmaceutically acceptable salt thereof. Another embodiment according to the invention is directed to treating of hyperiipidemia in a patient, comprising administering to the patient a therapeutically effective amount of a compound of Formula I, or a pharmaceutically acceptable salt thereof. Another embodiment according to the invention is directed to treating of hypertension in a patient, comprising administering to the patient a therapeutically effective amount of a compound of Formula I, or a pharmaceutically acceptable salt thereof. Another embodiment according to the invention is directed to treating eating disorders in a patient, comprising administering to the patient a therapeutically effective amount of a compound of Formula 1, or a pharmaceutically acceptable salt thereof. Treatment of eating disorders includes the regulation of appetite andor food intake in patients suffering from under-eating disorders such as anorexia nervosa as well as over-eating disorders such as obesity and anorexia bulimia. Another embodiment according to the invention is directed to treating a disease state associated with low levels of HDL comprising administering to the patient a therapeutically effective amount of a compound of Formula 1, or a pharmaceutically acceptable salt thereof. Diseases associated with low levels of HDL include atherosclerotic diseases. Another embodiment according to the invention is directed to treating polycystic ovary syndrome comprising administering to the patient a therapeutically effective amount of a compound of Formula I, or a pharmaceutically acceptable salt thereof. Another embodiment according to the invention is directed to treating climacteric comprising administering to the patient a therapeutically effective amount of a compound of Formula I. or a pharmaceutically acceptable salt thereof. Another embodiment according to the invention is directed to treating inflammatory diseases such as rheumatoid arthritis, chronic obstructive pulmonary disease (emphysema or chronic bronchitis), or asthma comprising administering to the patient a therapeutically effective amount of a compound of Formula I, or a pharmaceutically acceptable salt thereof Another aspect of the invention is to provide a novel pharmaceutical composition which is effective, in and of itself, for utilization in a beneficial combination therapy because it includes a plurality of active ingredients which may be utilized in accordance with the invention. In another aspect, the present invention provides a method for treating a disease State in a patient, wherein the disease is associated with a physiological detrimental level of insulin, glucose, free fatty acids (FFA), or triglycerides, in the blood, comprising administering to the patient a therapeutically effective amount of a compound of Fontiula I, and also administering a therapeutically effective amount of an additional hypoglycemic agent. In another aspect, the present invention provides a method for treating a disease state in a paCient, wherein the disease is associated with a physiological detrimental level of insulin, glucose, free fatty acids (FFA), or triglycerides, in the blood, comprising administering to the patient a therapeutically effective amount of a compound of Formula 1, and also administering a therapeutically effective amount of a biguanidine compound. In another aspect, the present invention provides a method for treating a disease state in a patient, wherein the disease is associated with a physiological detrimental level of insulin, glucose, free fatty acids (FFA.), or triglycerides, in the blood, comprising administering to tiie patient a therapeutically effective amount of a compound of Formula I, and also administering a therapeutically effective amount of metformin. The invention also provides kits or single packages combining two or more active ingredients useful in treating the disease. A kit may provide (alone or in combinaticm with a phannaceutically acceptable diluent or carrier), a compound of Formula (t) and an additional hypogl3'caeniic agent (alone or in combination with diluent or carrier). There are many known hypoglycemic agents in the art, for example, insulin; biguanidines, such as metformin and buformin; sulfonylureas, such as acetohexamide, chloropropamide, tolazamide, tolbutamide, glyburide, glypizide and glyclazide; thiazolidinediones, such as troglitazone; a-glycosidase inhibitors, such as acarbose and miglatot; and 83 adrenoreceptor agonists such as €1^316, 243. Since sulfonylureas are known to be capable of stimulating insulin release, but are not capable of acting on insulin resistance, and compounds of Formula I are able to act on insulin resistance, it is envisaged that a combination of these medicaments could be used as a remedy for conditions associated with both deficiency in insulin secretion and insulin'resistance. Therefore, the invention also provides a method of treating diabetes mellitus of type II in a patient comprising administering a compound of Formula I and one or more additional hypoglycemic agents selected from the group consisting of sulfonylureas, biguanidines, thiazolidinediones, Bj-adrenoreceptor agonists, a-glycosidase inhibitors and insulin. The invention also provides a method of treating diabetes mellitus of type II in a patient comprising administering 3 compound of Formula I and a sulfonylurea selected from the group consisting of acetohexamide, chlorpropamide, tolazamide, tolbutamide, glyburide, glypizide and glyclazide. The invention also provides a method of treating diabetes mellitus of type 11 in a patient comprising administering a compound of Formula i and a biguanidine selected from the group consisting of metformin and bufomiin. The invention also provides a method of treating diabetes mellitiis of type 11 in a patient comprising adminisiering a compound of Fonnula 1 and an a-glycosidase inhibitor selected from the group consisting acarbose and migiatol. The invention also provides a method of treating diabetes mellitus of type il in a patient comprising administering a compound of Formula 1 and an thiazoiidJnedione, for example, troglitazone. As indicated above, a compound of Formula I may be administered alone or in combination with one or more additional hypoglycemic agents. Combination therapy includes administration of a single pharmaceutical dosage formulation which contains a compound of Formula 1 and one or more additional hypoglycemic agent, as well as administration of the compound of Formula I and each additional hypoglycemic agents in its own separate pharmaceutical dosage formulation. For example, a compound of Formula 1 and hypoglycemic agent can be administered to the patient together in a single oral dosage composition such as a tablet or capsule, or each agent administered in sepju^te oral dosage formulations. Where separate dosage formulations are used, the compound of Formula I and one or more additional hypoglycemic agents can be administered at essentially the same time, i.e., concurrently, or at separately staggered times, i.e., sequentially. For example, the compound of Formula i may be administered in combination with one or more of the following additional hypMDglycemic agents: insulin; biguanidines such as melfonnin or buformin; sulfonylureas such as acetohexamide, chloropropamide, tolazamide, tolbutamide, glyburide, glypizide or glyclazide; thtazolidinediones such as troglitazone; a-glycosidase inhibitors such as acarbose or migiatol; or Bjadrenoreceptor agonists such as CL-316, 243. The compound of Formula I is preferably administered with a biguanidine, in particular, metformin. The compounds of Formula I contain at least three aromatic or hetero-aromatic rings, which may be designated as shown in Formula U below, and for which their substitution pattern along the chain with respect to each other also is shown below. from quinoliny!, benzothiophenyl, benzoimidazoSyl, quinazoiinyl, benzothiazoiyi, quinoxalinyl, naphthyl. pyridy!,! H-indazolyl, 1,2.3.4-tetrahyciroquinoimyl. benzofuranyl, thienyl, or indolyl, and one end of the membered aryl or heteroary!, and has a preferred position of attachment of Linker 11 and Linker III to Ring III at positions 1,4- to each other. A fiirther preferred aspect of the compound of Formula II is described by Formula V below: Another aspect of this invention is a compound of the invention wherein a = 0; A is -NR13-, b = 1, R3 and R4 are hydrogen. Another aspect of this invention is a compound of the invention wherein a = 2; vicinal Ri radicals taken together with the carbon atoms to which the Ri radicals are linked form an ethylene group; R2 is hydrogen; A is a chemical bond; and b=0. Another aspect of this invention is a compound of the invention wherein a = 1, 2 or 3; R| and Ri are hydrogen; A is -0-: and b = 0- Another aspect of this invention is a compound of the invention wherein a= 1; R|, Ri, R3 and R4 are hydrogen; A is -0-; and b = 1. Another aspect of this invention is a compound of the invention wherein c = 1 or 2; R5 and Rfi are hydrogen or alkyl; B.is a chemical bond; and d = 0. Another aspect of this invention is a compound of the invention wherein c = 2; vicinal R5 radicals taken together with the carbon atoms to which the R5 radicals are linked form an ethylene group; R^ is hydrogen; B is a chemical bond; and d=0. Another aspect of this invention is a compound of the invention wherein c = 0 or 1; Rj and Ri are hydrogen; B is -0-; and d = 0 or 1. Another aspect of this invention is a compound of the invention wherein c = 0; B is -C(Oy or -S(0)2-; d = 1 and R7 and R« are independently hydrogen or alkyl. Another aspect of this invention is a compound of the invention wherein e = 0; f = 0; D and E is a chemical bond; Z is R21O2SHNCO-, and R21 is phenyl. Another aspect of this invention is a compound ofthe invention wherein e = 0; f=Oor 1; D and E is a chemical bond; Z is telrazolyl, NH2CO- or -C02R2t; and R21 is hydrogen or lower alkyl- Another aspect of this invention is acompoundof the invention wherein e = 0; f=Oor 1; D is -O- or a chemical bond; E is a chemical bond; and Z is tetrazolyl, NH2CO- or -CO2R21; and R21 is hydrogen or lower alkyl. Another aspect of this invention is a compound ofthe invention wherein e = 0; f = 1; Dis -O- or a chemical bond; E is a chemical bond; Ri 1 and R12 are hydrogen or alkyl; and Z is tetrazolyl, NH2CO- or "CO2R21; and R21 is hydrogen or lower alkyl. Another aspect of this invention is a compound ofthe invention wherein e = 2, then vicinal R9 radicals taken together with the carbon atoms to which the R9 radicals are linked fomi an ethylene group; f= 0;DandE is a chemical bond; and Z is-C02R2i; andR2i is hydrogen. Another aspect of this invention is a compound ofthe invention wherein e = 0; f = 3; D is -0-; E is a chemical bond; Ru andR!2 are hydrogen or alkyl, or at least one of Ru is carboxyi or alkoxycarbpnyi; Z is telrazolyl, or -CO2R21; and R21 is hydrogen or lower alkyl. Another aspect of this invention is a compound of the invention wherein e = 0; f = 1, 2, or 3; D is -C(0)-; E is a chemical bond; R| \ and Ru are hydrogen or alkyl; Z is tetrazolyl or -CO3R21; and R21 is hydrogen or lower alkyl. an optionally substituted quinoHnyl, quinoxalinyl, quinazolinyl, isoquinolinyl, A'-alkyl-quinoIin-4-onyl, quinazoIin-4-onyl, benzoxazolyl, benzimidazolyl, benzothiazolyl, benzofuranyl, benzothiophenyl, indoHnyl oxazolyl, thiazolyl, oxadiazolyl isoxazolyl, imidazolyl, pyrazol-yl, thiadiazolyl, triazolyl, pyridyl pyrimidinyl, pyrazinyl, pyridazinyl, phenyl, or napthalenyl group, wherein the substituent is a ring system substituenl as defined herein, more preferably a substituent selected from the group consisting of phenyl, substituted-phenyl, ihienyl, substituted thienyl, cycloalkyl, lower alkyl, branched alkyl, fluoro, chioro, alkoxy, aralkyloxy, trifluoromethyl and trifluoromethyloxy. A more preferred aspect of this invention is a compound of the invention wherein 6-substituted quinolin-2-yl or 7 substituted quinolin-2-yl; an unsubstituted quinozalin-2-y!, 3-substituted quino2aIin-2-yI, 6-substituted quiDOzalin-2-yl or 3,6-disubstituted quinozaIin-2-yl; unsubstituted quinazo!in-2-yl, 4-substituted quinazolin-2-yI or 6-substituted quinazoIin-2-yl; unsubstituted isoquinolin-3-y!, 6-substituted isoquinolin-3-yi or 7-substiluted isoquinolin-3-yl; 3-substituted-qmnazolin-4-on-2-yl; 7*/-substiluted quinolin-4-on-2-yl; 2-substituted-oxazol-4-yl or 2,5 disubstituted-oxa2ol-4-yl; 4-substituted oxa20l-2-yl or 4,5-disubstituted-oxazol-2-yl; 2-substituied thia2ol-4-yl or 2,5-disubstituted thiazoI-4-yl; 4-substituted thiazol-2-yl or 4,5-disubstituted-thiazol-2-yi; 5-substituted-[l,2,4]oxadiazoI-3-yl; 3-substituted-[l,2,4] oxadiazol-5-yl; 5-substituted-imidazol-2-yl or 3,5-disubstituted-imidazol-2-yl; 2-sibstituted-imidazol-5-yl or 23-disubstituted-imidazol-5-yl; 3-substituted-isoxazol-5-yU 5-substituted-isoxa2ol-3-yl; 5-substituted-[l,2,4] tluadia2ol-3-yl; 3-substituted-[l,2,4]-thiadiazol-5-yl; 2-substituted-[I,3,4]-thiadia2ol-5-yl; 2-substituted-[l,3,4]HDxadia2ol-5-yl; l-substituted-pyrazol-3-yl; 3-substituted-pyia2Dl-5-yl; 3-subsiituted-[l,2,4]-triazol-5-yI; l-substituted-[l,2,4]-tria2ol-3-yl; 3-substituted pyTidin-2-yl, 5-substituted pyridin-2-yl, 6-substituted pyridin-2-yl or 3,5-disubstituted pyridin-2-yl; 3-substituted pyr22in-2-yl, 5-subsiituted pyrazin-2-yl, 6-substituted pyrazin-2-yl or 3,5 disubstituted-pyrazin-2-yl; 5-substituted pyrimidin-2-yI or 6-substiiuted-pyrimidin-2-yl; 6-substituted-pyrida2in-3-yl or4,6-disubstituted-pyridazin-3-yl; unsubstituted napthaien-2-yl, 3-substituted napthalen-2-yl, 4-substiiuted napthalen-2-yl, 6-substiluted napthalen-2-yl or 7 substituted napthaien-2-yl; 2-substituted phenyl 4-subsiituted phenyl or 2,4-disubstituted phenyl: unsubstiiuted -ben2othiazol-2-yl or 5-substituted-beiizothia2ol-2-yl; unsubsiituted benzoxazol-2yi or 5-substituted-ben2oxazol-2yi; unsubsiituted -benzimidazo!-2-yl or 5-substituted-ben2imida2ol-2-yl; unsubstiiuted -tliiophen-2yl, 3-substiruted -thiophen-2yI, 6-subsUtuted -thiophen-2y! or 3,6-disubstituted-thiophen-2yl; imsubstituted -benzofQran-2-y, 3-substituted-benzofuran-2-yl, 6-substiiuted-ben2ofiiran-2-yl or 3,6-disubstituted-benzoftiraii-2-yl; 3-substituled-benzofuxan-6-yI or 3,7-disubsiituted-benzQfuran-6-yl, wherein the substituent is a ring system substituent as defined herein, more preferably a substituent selected &om the group consisting of phenyl, substituied-phenyl, thienyl, substituted thienyi, cycioalkyl, lower alkyl, branched alkyl, fluoro, chloro, alkoxy, aralkyloxy, trifluoromethyl and trifiuoromethyloxy. Another more preferred aspect of this invention is a compound of the invention wherein Ri and Rj are both H, a = 1, A is -O- and b = 0. Another more preferred aspect of this invention is a compound of the invention w^ierein Ri andRiarebothH, a = 2,Ais-O-andb = 0. Another more preferred aspect of this invention is a compound of the invention wherein a = 0, A is -O- or -NRi3-; R13 is hydrogen or alkyl; R3 and R, are both independently hydrogen; and b = 1. Another more preferred aspect of this invention is a compound of the invention wherein a = 0, A is -O- or -NR13-; Ri3 is hydrogen or alky!; R3 and R4 are both independently hydrogen; b = 1; and Arl is 3-substituted quinolin-2-yl, 4-substituted qmnolin-2-yl, 6-substituted quinolin-2-yl, 7 substituted quinolin-2-yi, unsubstituted quinoxaIin-2-yl, 3-substituted quinoxalin-2-yl, 6-substituted quinoxaIin-2-yI, 3,6-disubstituted quinoxaJin-2-yi, imsubstituted qiuna2oIin-2-yI, 4-substiiuted quinazolin-2-yl, 6-subsiituted quinazolin-2-yl, unsubsiituted isoquinolin-3-y!, 6-substituted isoquinolin-3-yl, 7-substituted isoquinoIin-3-yl, 4-substituted oxazol-2-yl, 4,5-disubstituted-oxa2ol-2-yl, 4-substituted-thiazoI-2-yl, 4^-disubstituted-thiazol-2-yl, 5-subsdtuted -imida2oi-2-y!, 3,5-disubstituted-imida2oI-2-yl, l-substituted-pyrazol-3-yl, 3-substituted-pyiazoi-S-yl, 3-substituted pyTidin-2-yl, 5-substituted pyridin-2-yl, 6-substituted pyridin-2-yl or 3,5-disubstituted pyridin-2-y!, 3-substituted pyrazin-2-yl, 5-substituted pyra2in-2-yl, 6-substituled pyra2in-2-yl, 3,5 disubstituted-pyra2in-2-yl, 5-substituted pyrimidin-2-yl, 6-substituted-pyrimidin-2-yl, 6-substituted-pyridazin-3-yl, 4,6-disubstinjted-pyTida2in-3-yl, unsubsiitiited-benzothia2o]-2-yl, 5-substinjJed-be7:zothia2ol-2-y], unsubstituted-benzoxazo3-2-y3, 5-subsiituted-benzoxazoi-2-yl, unsubstituted ben2imida2ol-2-yI, 5-substituied-benzimidazol-2-yL 3-substituted-benzofuran-6-y! or 3,7-disubstituted-benzofiiran-6-yl. .Ajiother aspect of this invention is a compound of formula I as described by formula (la) below: aiyiheterocyclcnyl, fused aiylheterocyclyl, heteroaryl, fused heteroaiylcycloalkenyl, fused heteroarylcycioalkyl, fiised heteroaiylheterocyclenyl, or fused heteroarylheterocyclyl; c+d = I or 2; Bis-O-; Rs, Rfc R7, Rg are independently hydrogen; e = 0; f=0; D and E are a chemical bond; Z is R21O2C-, R21OC-, cyclo-imide, -CN, R21O2SHNCO-, R21O2SHN-, (R2i)2NCO-, KnO- 2,4- thiazolidinedionyl, or tetrazolyl; R' and R" are ring system substituents as defined herein, more preferably, R' is lower alkyl, halo, alkoxy, aryloxy or aralkyl; and R" is lower alkyl or halo. Another aspect of this invention is a compound of formula i as described by formula (la) below: aryiheterocyclenyl, fused arylheterocyclyl, heteioaiyl, fused heteroaiylcycloalkenyl, fused heteroaiyicycloalkyi, fiised heteroarylheterocyclenyl, or fused heteroaiyiheterocyclyl; c+d = I or 2; Bis-0-; Rs, Rfc R.7, R« are independently hydrogen; e=0; f=0; D and £ are a chemical bond; Zis-COaH; R' and R" are ring system substituents as defined herein, more preferably, R' is lower alkyl, halo, alkoxy, aryloxy or aralkyi; and R" is lower alkyl or halo. Another aspect of this invention is a compound of formula I as described by formula (la) below; 3 = 0-2; b = 0-l; 5 Ais-0-or-NRi3-; c+d = 1 or 2; Bis-O-; Ri, R2, R3, R4 Rs, R*, R7, and Ra are independently hydrogen; Ri3 is hydrogen, R22OC-, or alkyl; ) e = 0; f=0; D and E are a chemical bond; 2 is -CO2H; R' and R" are ring system substituents as defined herein, more preferably, R' is lower alkyl, > halo, alkoxy, aryloxy or aralkyl; and R" is lower alkyl or faalo. A more preferred aspect of this invention is a compound of formula I as described by formula (la) wherein: a = 1 or 2; ) A is -0-; b = 0; Ri, R2. R? and Rg are independently hydrogen; B is -0-; d=l; e = 0; f=0; D and E are a chemical bond; R' is hydrogen, halo or benzyloxy; R" is lower alkyl, preferably methyl; Z is-COiH. A more preferred aspect of this invention is a compound of formula I as described by fomiula (la) wherein: a = I or 2; A is -0-; b = 0; Ri, R2. R5 and R^ are independently hydrogen; B is -0-; d = 0; e = 0; f=0; D and E are a chemical bond; R' is hydrogen, halo or benzyloxy; R" is lower alkyl, preferably methyl; Z is-C02H. A more preferred aspect of this invention is a compound of formula I as described bv formula (la) wherein; a = 1 or 2; A is -0-; 5 b = 0; R-i, R2.R-7, R-s, Rii andRi2 are independently hydrogen; c = 0; B is -0-; ) d=U e = 0; D and E are a chemical bond; R' is halo; > R" is lower alkyl, preferably methyl; Z i5-C02H. A more preferred aspect of this invention is a compotmd of formula I as described by formula (la) wherein: b = 0; c = 0-l; Bis-0-; d = 0 or 1, wherein c+d = 1 or 2; e = 0; f=0; D and E are a chemical bond; R' is hydrogen, aralkoxy, or halo; R." is lower alkyl, preferably methyl; 2 is -CO;H. A more preferred aspect of this invention is a compound of formula I as described by formula (la) wherein: ■ a=I; A is -0-; b = 0; c = 0; B is -0-; d=I; e = 0; f=0; D and £ are a chemical bond; R' is hydrogen; R" is lower alkyl; Zis-COjH. A more preferred aspect of this invention is a compound of formula I as described by formula (la) wiurein: A is -0-; b = 0; c = 0: B is -0-; d=l; e = 0; f=0; D and E are a chemical bond; R' is hydrogen; R" is lower alkyi; Z is 'CO2H. A more preferred aspect of this invention is a compound of fonnuia I as described by fonnula (la) wherein: a=l; A is -0-; b = 0; I c = 0; B is -0-; d=l; e=0; f=0; D and E are a chemical bond; R' is hydrogen; R" is lower alkyl; Z is CO2H. A more preferred aspect of this invention is a compound of formula I'as described by fonnula (la) wherein: heteroaryl group is substituted by optionally substituted phenyl or optionally substituted cyciohexyl; Ais-0-; b-0; c = 0; Bis-O-; d= 1; e = 0; f=0; D and E are a chemical bond; R' is hydrogen; R" is lower alkyi; Z is CO2H. Compounds according to the invention are selected ^m the group consisting oF A preferred compound according to the invention that is selective for PPARa and PPAR5 is seiected from the group consisting of:This invention also encompasses all combinations of preferred aspects of the invention noted herein. Compounds useful according to this invention can be prepared in segments as is common to a long chain molecule. Thus it is convenient to synthesize these molecules by employing condensation reactions at the A, B and D sites of the molecule. Compounds of Formula I can be prepared by the application or adaptation of known methods, by which is meant methods used heretofore or described in the literature. Compounds of Formula I are preparabie by recognized procedures from known compounds or readily preparabie intermediates. Thus, in order to prepare a compound of the below formula, where Z is generally CN or COiR The following reactions or combinations of reactions are employable: In the above schemes (1-3) a displacement reaction can be used when A, B and D are O, S or NR, and L is a leaving group such as halo, toslyate or mesylate. A base such as sodium hydride, sodium hydroxide, potassium carbonate or triethylamine may be used when A, B or D is O or S. An alternative coupling reaction is the Mitsunobu reaction (diethylazodicarboxylate/triphcnylphosphine see Synthesis, 1981, ]). This chemistry can be used to condense fragments when the functionality is amenable to this reaction. An example of this would be the coupling of compounds of scheme 1 where formula VI (L = OH, a > 0) and formula VII (A = O, b - 0) Reaction temperatures are in the range of about -78 °C to 80 °C and reaction times vary from about 1 to 48 hours- The reactions are usually carried out in an inert solvent that will dissolve the veactants. Solvents include, but are not limited to N,N-dimethylformamide, acetone, acetonitrile, tetrahydrofuran. Alternatively, the reactions shown in Schemes I -3 can be accomplished using a fragment of the described Formula. For example, as shown in Scheme 4, a compound of Formula VI (Scheme 1) may be combined with a compound of Formula VII, where Formula VII optionally contains Ar III and Z. This notation used for Formula Vll in Scheme 4 is used throughout this document and is used to generalize the described reaction. Therefore, all of the reactions of Schemes 1-3 may be accomplished as shown or by using a fragment of the described formula. In some instances, the use of a protecting group may be required when a fragment of a formula is used. One method for the preparation of compounds where Z = tetrazole is the reaction of an intermediate where Z = CN with sodium azide and ammonium chloride at an elevated temperature. One method for the preparation of compounds where 2 = C03H. is the hydrolysis of an intermediate where 2 is CN or COjR. This can be accomplished under acidic or basic conditions, with the preferred method generally being sodium or potassium hydroxide in a protic solvent such as aqueous ethanol at a temperature of about 20 °C to 100 °C. An alternative method for the conversion of a nitrile to a carboxylic acid is to reduce the nitrite to the corresponding aldehyde using a reducing agent such as diisobutylaluminum hydride, followed by oxidation of the aldehyde to the carboxylic acid using a reagent such as sodium chlorite, sodium dihydrogen phosphate, isobutene (See, J ACS 1980, 45, 1176) or other standard conditions. Another alternative method .For the preparation of compounds where Z = CO.H is the oxidation of a primary alcohol using an appropriate oxidant such as PDC in DMF. RuCI:. /Nal04 in 3:2:2 water aceionitrile : CClt or the Swem system (to produce the intermediate aldehyde rheii oxidation of this functionality to the carboxylic acid as described above). Some other methods for the preparation of compounds where Z = C02H are shown in Scheme 5 . A carboxylic acid (2) can be generated directly by halogen-metal exchange of the corresponding aromatic halide (I) with an alkyl lithium reagent such as n-butyliithium, followed by quenching the resulting anion with carbon dioxide. Alternatively, alkoxy-carbonyiation of an aromatic bromide, iodide or triflate can be accomplished in a carbon monoxide atmosphere in the presence of a suitable alcohol (usually methanol) using a catalyst such as Pd(PPh;hC1: / Et.NH. Pd(Ph;P(CH,)?PPh:): / Ei..N or alternatively cobalt, ie. CoCOAc)!, plus a base (NaH or KJCOJ). The resulting benzoate (3) is then converted to the benzoic acid by hydrolysis as described above. Preparation of phenvlacetic acid dcrhaiivcs can be accomplished from an appropriate aryl halide or triflate as illustrated in Scheme 6. Stille coupling of this type of compound with a vinyl stannane using a palladium catalyst such as Pd(0 Ac) i, P(o-tolyl)3 provides an olefin. (5). Hydroboration of this vinylbenzene dmvam c, followed by oxidation of the resulting primary alcohol with an oxidant, such as Jones' reagent, provides the phenylacetic acid (6). In one embodiment of the current invention, Arl can be a five membered ring heterocycle thus generating astructures of the general form shown in Figure 1. Figure ! In particular, the heterocycle can be a substituted thiazole, oxazole, oxadiazole, imidazole, isoxazole, pyrazole, thiadiazole ortriazole. These systems can be prepared using methods known in the chemical literature (for reviews see Katritzky, A.R.; Rees, C.W. Eds. Comprehensive Heterocyclic Chemstry, Vol. 5; Pergamon Press (1984); Katritzky, A.R.; Rees, C.W.; Scriven, E.F.V. Eds. Comprehensive Heterocyclic Chemstry II; Vols 3 & 4, Pergamon Press (1996)). More specifically, oxazoles, imidazoles and thiazoles can be prepared by fusion of an amide, amidine or a thioamide, respectively, with an «-halo-ketone at temperatures ranging from about 40 °C to 150 °C (Scheme 7). These reactions may be carried out neat, or in a solvent such as toluene, dichlorobenzene, or ethanol. Substituted oxazoles can also be prepared from a diazoketone and a nitrile using BFj etherate (Scheme 8), Ibata,T; Isogami, Y. Bull. Chem. Soc. Jpn. 1989, 62, 618). 1,2,4-OxadiaxoIes can be prepared by reaction of a nitrile with hydroxylamine followed by condensation of the resulting hydroxy-amidine with an acid chloride in the presence of a base and heating the adduct in a solvent such as toluene or dichlorobenzene to effect ring closure*. (Scheme 9, Banavara, L.M.; Beyer, T.A.; Scott, PJ.; Aldinger, C.E.; Dee, M.F.; siegel, T.W.; Zembrowsky, WJ. J. Med Chem., 1992, 35, 457). 1,3,4-oxadiazsoIes are prepared (Scheme 10) by condensation of an acylhydrazide witfi an acid synthon (such as an ester, acid chloride acyl azide) then cyclization of the resulting diacyl-hydrazide by heating in a solvent such as benzene or ethanol with or without an acid catalyst such as sulphuric acid (for examples see Weidinger, H.; Kranz, J. Chem. Ber.. 1963, 96, 1049 and Vakula. T.R.; Srinivarsan, V.R. Indian J. Chem.. 1973, II. 112). Substituted 1,2,4-thiadiazoles can be prepared by condensation of a thioamide widi an N,N-dtmethylamide dimethyl acetal derivative in a solvent such as benzene (Scheme 11, MacLeod, A.; Baker, R.; Freedman, S.F.; Patel, S.; Merchant, K.J.; Roe, M. Saunders, J. J. Med Chem., 1990, 33,2052. also Patzel, M. Liebscher, J.; Siegfried, A. Schmitz, E. Synthesis, 1990, 1071) followed by reaction with an electrophilic aminating agent such as mesitylsulphonyloxyamine in methanol or dialkyloxaziridine in a solvent such as toluene. In another embodiment of this invention Aricanbea 1,3,4-thiadiazole. This system is assembled by condensation of a dithioester with an imidate ester salt in a solvent such as ethanol at a temperature between room temperature and reflux (Scheme 12. StUlmgs, M.R.; Welboum, A.P.; Walter, D.S. /. Med. Chem., 1986,29,2280). The dithioester precursor is obtained from the corresponding Grignard reagent and carbon disulphide / Mel. The imtdate ester is prepared from the corresponding nitrile by reaction with HCi gas in the presence of an appropriate alcohol. Pyrazoles can be prepared by condensation of a 1,3-diketone (Scheme 13) or a synthetic equivalent with a substituted hydrazine (for example, a p-aminoenone. Alberola, A.; Calvo, L.; Ortega, A.G..; Sadaba, MX-; Sanudo, M.C.; Granda, S.G.; Rodriguez, E.G., Heterocycles, 1999, 51, 2675). Similarly, isoxazoles can be prepared by reaction of a 1,3 dicarbonyl compound with hydroxyl amine (Scheme 14. Pei, Y.; Wickham, B.O.S.; Tetrahedron Letts, 1993, 34, 7509) in a solvent such as ethanol a a temperature between 20 °C to reflux temperature. Alternatively, isoxazoles can be prepared by condensation of a hydroxanwl chloride with an alkyne (Scheme 15, Kano, H.; Adachi, !.; Kido, R.; Hirose, K. J.Med. Chem. 1967. 10, 411) in the presence o a base such as triethyiamine. The hydroxamyl chloride unit can, in turn, be prepared from the corresponding oxime by oxidation with chlorine gas at low temperature (such as -60 °C) in a solvent such as ether (Casanti, G. Ricca, A. Tetrahedron Lett., 1967, 4, 327). Triazoles are prepared by the Einhorn-Bnmner reaction or a variant thereof (Scheme J 6) In addition, 5-hydroxymethyl substituted 1,2,4-triazoles can be prepared by condensation of an imidate ester with an 2-hydroxy-acetohydrazide unit (Scheme 17. Browne, E. J.;Nunn, E. E-; Polya, J. B.J. Chem.Soc.,C 1970, 1515). The five membered heterocycles, so formed, can, in certain cases, be coupled directly with a fragment containing Aril using standard methodology detailed elsewhere in the description of this invention (Schemes 1-4). These methods include alkylation of metal alkoxide containing Aril with a chloromethyl substituted heterocycle, or conversely, alkylation of a hydroxyl appended heterocycle (in the presence of a base) with a chloromethyl reagent containing Aril. In another approach to fragment condensation, the substituents on the preformed heterocycle are first modified to incorporate suitable reactive functionality then this system is coupled to a fragment containing Aril. FOT example (Scheme 18), treatment of a 1 ,4-disubstituted imidazole with a base such as n-butyl lithium at a temperature of around -78 °C followed by alkylation of the resulting anion with an electrophiie such as ethylene oxide provides the hydroxyethyl-substituted imidazole {other useful electrophiles are DMF or formaldehyde. For example see Manoharan, T.S.; Brown, R.S. J. Org. Chetn., 1989, 54, 1439). This intermediate can then be coupled to an Aril fragment containing an aromatic alcohol via a Mitsunobu reaction. Another example of this genera! approach is shown in Scheme 19. A ring substituent such as an ester can be reduced to the corresponding alcohol using a reagent such as lithium aluminum hydride or lithium borohydride in a solvent such as THF or ether. Followed by halogenation of the resulting alcohol with a reagent system such as NCS / Ph3P, Ph3P / Br2 or PBr3 (Pei, Y.; Wickham, B.O.S.; Tetrahedron Lett., 1993, 34, 7509). The alkyl halide produced in this manner can be coupled with a nucleophilic substituent attached to Aril, using a base such as K2CO3 in the case of an aromatic alcohol, (thiol) or NaH in the case of an aliphatic alcohol (thiol). in a third general approach to fragment condensation, Ar II can be incorporated into a precursor of the five membered heterocycle. For example (Scheme 20), animation of the 3-aryl-propionate and thionation of the resulting amide provides a suitable functionalized system for thiazole ring synthesis. Similarly formation of the thio-urea from the arylmethyl amine (path B) provides a suitable precursor for fusion with an ?-haloketone leading to a 2-amino-substituted diiazole (Collins, JX.; Blanchard, S- G.; Boswell, G. E.; Charifson, P. S.; Cobb, J. E.; Henke, B. R.; Hull-Ryde, E. A.; Kazmierski, W. M.; Lake, D. H.; Leesnitzer, L. M.; Lehmann, J.; Lenhard, J. M.; Orband-Miller L.A.; Gray-Nunez, Y.; Parks, D. J.; plimkett, K. D.; Tong, Wei-Qin. J. Med. Chem. 1998, 41, 5037). In another embodiment of this invention, Arl is a five membered heterocycle of general formula shown in Figure 2. W ■ CRlr N; X - CRi. N; Y= CR,. N; Z ~ CR, N Provided that when A = O, N, or S then "a" is > 1 Figure 2 In particular, this heterocycle can be a pyrazole, an imidazole or a triazole. These systems can be prepared by alkylation of an Af-unsubstituted heterocycle using a base such as sodium hydride, in a solvent such as DMF, THF, DMPU or a combination of these solvents, at or around 0 °C and an electrophile such as an alkyl halide, cyclic carbonate or an epoxide (Scheme 21). These electrophiles can incorporate Aril or the alkylation products can be further modified and coupled to a fragment containing Aril in a subsequent step as described above. For example (Scheme 22), The 3,5-disubstituted pyrazole is prepared by reacting an aldehyde with a {J-tosylhydrazinophosphonate, using the literature procedure (Almirante, N.; Benicchio, A.; Ccni, A.; Fedrizzi, G.; Marazzi, G.; Santagostmc, M. Synleti 1999, 299). This intermediate can then be alkylated with sodium hydride / ethylene carbonate in DMF (for a specific example see Collins, J.L.; Blanchard, S. G.; Boswell, G. E.; Charifson, P. S.; Cobb, J. E.; Henke, B. R.; Hull-Ryde, E. A.; Kazmierski, W. M.; Lake, D. H.; Leesnitzer, L. M.; Lehmann, J.; Lenhard, J. M.; Orband-Miller L.A.; Gray-Nunez, Y.; Parks, D. J.; Plunkett, K. D.; Tong, Wei-Qin. J. Med. Chem. 1998, 41, 5037). This intermediate can in mm be coupled to a fragment containing Aril by a Mitsunobu reaction as described above. Scheme 22 In another embodiment of this invention Arl is a substituted benzene, pyridine, pyrimidme, pyrazme or pyridazine (Figure 3). These systems can be prepared by applying several of the general synthetic methods detailed elsewhere in the description of this invention. More specifically (Scheme 23), treatment of the known 5-bromo-2-methyl-pyridine (Graf. J. Praia. Chem., 1932,133, 19.) with LDA then formaldehyde in THF at low temperature (typically around -78 °C) followed by Mitsunobu coupling of the resulting alcohol to an aromatic alcohol containing Aril gives the bromo-pyridine derivative which can be further modified to give various alkyl and aryl substituted pyridines by cross coupling with an appropriate alkyl or aryl organometallic under palladium or nickel , catalysis (For general reviews see Knight, D.W. and Billington, D.C in Comprehensive Organic Synthesis Vol. 3, p 413 and 481, Trost, B.M. and Fleming, I; Eds. Pergamon Press 1993). Similar procedures using the appropriate 5-bromo-2-methyi-pyrimidine (Kosoiapoff, G.M.; Roy, C.H. J. Org. Chem., 1961. 26. I 895), 2-iodo-5-methy|-pyrazine (Hirshberg, A.: Spoerr, P.E.;. J. Org. Chem., 1961, 26.1907) and 3-bromo-6-methyl-pyridazine (Counotte-Potman, A.; van der Plas. H.C.; J. Heterocyclic Chem., 1983, 20, 1259) provide access to the corresponding pyrimidines, pyrazines and pyridazines respectively. In another variant of this general class, Arl is a 3-heteroatom-substituted pyridazine. For example (Scheme 24), treatment of the known 3,6-dibromo- pyridazine with a metal alkoxide (containing Aril and derived from the corresponding alcohol and sodium hydride) in a solvent such as DMSO provides the alkoxy-substituted bromo-pyridazine. The bromide can be convened into a range of substituents as described above for pyridines. In particular, Suzuki coupling with a boronic acid in the presence of a base and a palladium catalyst provides the corresponding aryl substituted pyridazines. In another embodiment of this invention Arl can be a substituted quinoxaline (Figure 4). These systems are assembled by condensation of a 1,2-dicarbonyf compound with a 1,2 diamino-benzene (for a review, see Kfltritzky, A.R.; Rees, C.W.; Striven, E.F.V, Eds. Comprehensive Heterocyclic Chemsny II; Vol 6 Pergamon Press (1996). Funetionalixation of these systems and coupling to Aril can be effected using procedures described for the related pyrazines. For example (Scheme 25), condensation of 1,2-diamino-benzene with 2,3-butadione provides the 2,3-dimethyI quinoxaline. A'-oxidation of this intermediate with a peroxy-carboxyiic acid and treatment of the product with acetyl chloride gives the 2-chloromethy 1-3 -methyl quinoxaoline (Ahmed, Y.; Habib, M.S.; Bakhtiari, B- Bakhtiari, Z. J. Org. Chem., 1966, 31, 2613). This intennediate is then coupled to a fragment containing Ar II under standard conditions. In another embodiment of the current invention Arl can be a quinazoline (Scheme 26). Such systems are commonly prepared by condensation of an o-amino-benzaldehyde or o-amino-aryl-kstone derivative with an acid chloride followed by heating with ammonia. For example, condensation of o-amino-benzaldehyde with chloroacetyl chloride in the presence of pyridine followed by reaction of the product with ethanolic ammonia at room temperature (Armarego, W.L.F.; Smith, J. I. C. J. Chem. Soc, C, 1966, 234) provides a 2-chloromethyI substituted quinazoline which can be coupled to a iragment containing Aril as described above. The related quinazoIin-4-one ring system (Scheme 27) can be prepared by condensation of an o-amino-benzonitrile and an acid chloride followed by ring closure using a reagent such as urea hydrogen peroxide in the presence of a base such as potassium carbonate (Bavetsias, y. Synth. Commxm. 1998, 28, 4547). In another variant of the quinazoline system, 4-heteroatom substituted quinazolines can be prepared by condensation of an amino-benzoniirile with chlorocetonitrile in the presence of an acid such as HCi or HBr(Chhabria,M. T.;Shishoo, C.J. Heierocycles 1999, 51, 2723.). The resulting system can be coupled to Aril as described above. The 4-halo-substituem can then be modified by nucleophilic displacement by a metal alkoxide in a solvent such as DMSO. > A general reaction for the preparation of reagents such compounds of formulas VI, IX, X XIII and XIV (schemes 1-3) is shown in Scheme 28. Halogenation of a methyl substituted aromatic with a reagent such as N-bromosuccinimide under free radical conditions provides the halomethyl substituted aromatic reagents. An alternative preparation of certain alkylating reagents is shown in Scheme 29. For example, substituted 2-chloromethyl quinoline derivatives can be prepared using a two step procedure (See, J. Med. Chem. 1991,34,3224). Oxidation of the nitrogen to form the N-oxide can be acheived with an oxidant such as m-chloroperbenzoic acid or hydrogen peroxide. Reaction of the N:oxide with a reagent such as toluene sulfonylchloride at elevated temperatures can produce the target chloromethyl derivative. This chemistry can also be extended to 2-picoline derivatives where the 6-position is non-hydrogen. Preparation of reagents which can be used as alkylating agenets of formula VI (scheme 1) are shown in Scheme 30. With the quinoxaline ring system the use of trichloroisocyanuric acid (TCC) can produce the corresponding chloromethyl analog (See, Chem. Ber. 1987,120, 649). In a particular embodiment of this invention, B of Formula I can be an amide linker of eititerof the general forms shown in Figure 5. Compounds of this formula can be prepared from a carboxylic acid fragment and an amine fragment using standard peptide coupling reagents. They can also be prepared by reaction with an activated carboxylic acid derivative such as, but hot limited to, an acid chloride or anhydride in combination with an amine fragment in the presence of a suitable base such as triethylamine. It should be clear that essentially the same procedures can be used in the case where group A of Formula I is an amide using the appropriate carboxylic acid and amine fragments. More specifically, the 2-aminomethyl-6-substituted-benzoic acid system (7) can be prepared using the chemistry shown in Scheme 31. Selective reduction of the substituted Dhthalic anhvdride (9) with a sterically hindered lithium trial klyborohyd ride, such as L-seleciride; provides lactone (10) regioseiectively (See Krishnamurthy, Heterocycles, 1982,18, 4525). Reaction of this lactone with potassium phthaiimide provides the protected amine according to the procedure of Bomstein, Ors.Syn. Collective Vol IV, 1963, 810. Removal of the phthalimide protecting group using standard deprotectfon conditions with hydrazine can provide the amino acid (7). 1,2-Carboxylic acid-half esters such as 12 (Scheme 32) are precursors to amide linked structures (Figure 5) in which the Arlll containing fragment is the acyl doner. These systems can be prepared in several ways: Alcoholysis of the phthalic anhydride (9) can provide selectively isomer (11) plus smaller amounts of isomer (12). EsterificatiDn to provide the diester (13) can be accomplished using a variety of conditions, such as Fisher esterification. Hydrolysis of the diester can provide the regioisomer (12) as me major isomer in addition to isomer (II). Phthalic anhydride derivatives such as (9) can, in turn, be prepared from the corresponding diacid (14) as shown in Scheme 33 using dehydrating conditions such as, but not limited to. hot acetic anhydride. In one embodiment of this invention, ArllHCRpRioVEHCRtiRuVE-Z taken together constitutes a substituted benzoic acid. A useful sequence of reactions for constructing this kind of system is shown in Scheme 34. A lactone (obtained as described in Scheme 31) can be heated with hydrobromic acid to provide the bromomethyl carboxylic acid. The carboxylate can be esterified by preparing the acid chloride, followed by reaction with an alcohol to provide an intermediate bromide which can be used as outlined in Scheme 2, Formula XIII. An alternative benzoate substitution pattern can be accessed using the Aider-Rickert reaction as shown in Scheme 35 (See, J. Org. Chem. 1995, 60, 560). A 2-silyloxydiene can be formed from an enone using a strong base such as LDA and trapping the enolate with a silylating reagent. Heating this diene with an acetylenedicarboxylate at elevated temperatures can then yield the Alder-Rickert product. Alkylation of the phenolic hydroxy! under standard conditions (using the alkylating reagent R'-L, where L is a leaving group) followed by saponification of the diester can provide a diacid intermediate which can be manipulated according to the chemistry described in figures 31-34 to provide useful intermediates for the preparation of compounds of Formula I. Another particular embodiment of this invention is one in which the substituted benzoic acid moiety described above has a 6-aIkyl-2-aIkoxy substituent pattern. The preparation of this kind of system is illustrated using the 6-methyI derivative shown in Scheme 36 (See Hamada, Tetrahedron. 1991, 41, 8635). Ethyl acetoacetate and crotonaldehyde can be condensed to form the cyclic (3-ketoester. Subsequent lithium chloride / cupric chloride mediated aromatization of this intermediate can be accomplished at elevated temperatures to provide the target salicylate ester. The phenolic hydroxyl of this system can be further derivatized by alkylation as outlined elsewhere in the description of this invention. Additionally, 6-alkyl-2-aIkoxy benzoate systems can be prepared by aromatic nucleophilic substitution of a 2-fluorobenzaidehyde, at elevated temperatures, with an alkoxide (Scheme 37) to produce a 2-aIkoxy-benzaidehyde. Oxidation of the aldehyde to the acid can then be accomplished using conditions such as sodium chlorite, sodium dihydrogen phosphate, isobutene (See, JACS 1980, 45, 1176). In another embodiment of this invention, B of Formula I can be a sulfur atom forming a thioether linkage (Scheme 2, Formulas (XI and XII). This type of system can be prepared by standard thiol alkylation using a suitable base (such as sodium or potassium carbonate, hydroxide, hydride or an amine such as triethylamine) to form an anion of the thiol and then reaction of this species with an appropriate electrophile such as an alky! halide or sulphonaie ester. Similarly, the groups A and D of Formula I can also be, independently, a sulfur atom. It should be clear that he same transformations described in the Schemes below can be applied to compounds of Formulas (VII. VIII. XI. XII and XVI: schemes 1-3). Aromatic thiols can be prepared from the corresponding phenols. For example, preparation of a 2-thio-benzoate(IO) from the salicylate (7), can be carried out as shown in Scheme 38. (See, Guise J. Chem Soc, Perkin Trans. 1,1982, 8, 1637). The thionocarbamate (8) can be obtained from the corresponding phenol (7) using a thiocarbamoyl chloride. Pyrolysis of (8) (->300 °C) can yield the rearrangement product (9) which upom hydrolysis can yield the thiol (10). Another useful ring substituent transformation is the conversion of an aniline to an aromatic thiol. As shown in Scheme 39, diazotization of an aniline such as (11) is followed by conversion of the diazonium salt (12) to a disulfide(13) using sodium sulfide. Reduction of the disulfide with zinc/acetic acid can yield the thiol (14) (See, Guise J. Chem Soc, Perkin Trans. 1,1982, 5, 1637). In a particular embodiment of this invention, Arfll can be a halo-substituted aromatic. Synthesis of a particularly relevant system is outlined in scheme 40. Regioselective halogenatton of a 2,6-disubstituted-phenol to provide the 4-halophenol system can be accomplished with a halogenating reagent such as sulfuryl chloride (See, J. Het. Chem. 1989,26, 1547). The phenolic hydroxyl group can be further derivitized as outlined elsewhere in the description of this invention. Scheme 40 An alternative method for the preparation of a halo (or alkoxy Substituted benzoate is shown in Scheme 41. An aniline is first converted to its diazonium salt using nitrous acid, followed by transformation to the corresponding nitrile using a reagent such as cuprous cyanide (See Chem. Ber. 1983,116, 1183). The cyano group is then hydrolyzed to the acid (see, Fuson, JACS 1941, 63, 1679). The acid may then be protected as an ester to allow further derivitization of the system as outlined elsewhere in the description of this invention. X = halogen or alkoxy An ortho-haio-benzoate can be prepared similarly, by diazotization of an o-carboxy aniline, followed by reaction with a copper haltde (Scheme 42). In another embodiment of this invention, ArlH is a benzofuranyl or dihydrobenzofuranyl carboxylic acid as illustrated in Figure 6 Benzofuran-2-carboxylate derivatives can be prepared as shown in Scheme 43 by cyclization of the appropriately substituted 2-carbonyl-phenoxyacetate under basic conditions. Reduction of the resulting benzofuran to die corresponding 2,3-dihydro-benzofuran can be accomplished using sodium mercury amalgam under basic conditions. (See, J. Med Chem. 1984, 27, 570). An alternative synthesis of die 23-dihydrobenzofuran-2-carboxyIate ring system is shown in Scheme 44 (See, J. Med. Chem. 1981, 865). Claisen rearrangement of a substituted ailyl-phenyl ertier at an elevated temperature such as 250 °C either neat or in a solvent such as dimethylaniline, can provide die o-aliyl-phenol. Peracid oxidation of this intermediate provides the 2-hydroxymethyl-2^3-dihydroberizofuran. which can be further oxidized to the carboxylic acid using a variety of oxidizing agents such as Jones' reagent In anotfier embodiment of this invention "A" can be an imidazoiidin-2-one, a tetrahydropyrimidtn-2-one an imidazoline-2,4-dione, or a tetrahydropyrimidin-2,4-dinone (Figure 7). These systems are prepared from an amine containing Arl by sequential acylation, aminofysis, ring closure and reduction, as illustrated in Scheme 45 (For examples see Kitazaki, T.; asaka, A.; Tamura, K; Matsushita, Y.; Hosono, H.; Hayashi, R.; Okonogi, K.; Itoh, K. Chem. Pharm. Bull, 1999, 47, 351 and Basha, A.; Tetrahedron Lett., 1988, 29, 2525). Coupling to Aril can be effected by derivitization of the cyclic urea N by treatment with a base such as NaH in THF at around 0 °C then alkylation of the resulting anion with an electrophile such as an alkyl bromide / inflate containing Aril). In another embodiment of this invention Aril is a six membered ring aromatic of general form substituted shown in Figure R. In particular. Aril is a substituted benzene, pyridine, pyrimidint, pyridazine or pyrazine. In principle, appropriately functionaiized ring systems of this kind can be prepared by functionaiization of specific precursors followed by ring synthesis or by derivatization of a preformed ring system. There are numerous approaches to the synthesis and functionaiization of the aforementioned cyclic frameworks in the chemicai literature (for examples, see (a) Katritzky, A.R.; Rees. C.W.; Scriveti, E.F.V. Eds. Comprehensive Heterocyclic Chemstry II, Vol 5 and Vol 6. Elsevier Science 1996 and references therein). For example, (Scheme 46} alkylation of methyl glycolate with an alkyl halide containing Arl using a base such as sodium hydride in a solvent such as THF or DMSO provides the ester. Claisen condensation of this ester with r-butyl acetate at low temperature (typically below -15 ^C) using a base such as LDA in THF provides the keto ester intermediate. This is reacted with formamidlne acetate in the presence of a base such as sodium methoxide in methanol to give the pyrimidinone (Butters, M. J. Heterocyclic Chem., 1992,29, 1369). This type of substituted aromatic system can be further functionaiized to incorporate Arl as described elsewhere in the description of this invention. In certain cases, Aril (in Figure 8) can be assembled by ring transformation of another heterocycle, for example, treatment of the known 4-bromo-2-methoxy-furan (Scheme 47, Marin i-Bettolo, R-; Flecker, P.; Tsai, T. Y. R.; Wiesner, K.Can. J. Chem. 1981, 59, 1403) with an alkyl lithium at low temperature and reaction of this anion with an electrophile containing Arlll (such as a bromide, aldehyde, epoxide) provides the 4-substituted furan. Oxidative cleavage of this intermediate widi dioxirane followed by treatment with hydrazine provides the pyridazinone which can be further modified to incorporate Arl as illustrated elsewhere in die description of this invention. A particularly useful protocol with regard to functionalization of heterocycles involves Mitsunobu etherification of hydroxy) substituted heterocycles (or keto-tautomers) such as outlined in Scheme 48. Treatment of the known 6-brDmo-pyridJn-2-0ne (Wibaut, J.P.; Waayman, P.W.; Vaudijlt, J. Jtec. Trav. Chinu Pays-Bas. 1940,59, 202) with an alcohol containing an Arl (or Arlll) under Mitsunobu's conditions provides the corresponding bromo-substituted pyridyl ether, (for typical procedures see Mitsunobu. 0., Synthesis, 1981, 1). The heterocyclic bromide, so formed, can be further functionaiized in a number of ways. For example, coupling with a vinyi stannane can be effected under palladium (o) catalysis to provide systems with alkenyl linkers (Scheme 49). The choice of catalyst and reaction temperature for this transformation depends on the substrate employed but is most commonly tetrakistriphenylphosphine palladium.bis(triphenylphosphine)paIladium chloride, 1,1 '-bis(diphenyiphosphino)ferrocene/bis-dibenzy]ideneacetone palladium or 1,2 bis-(diphenylphosphino)ethane/bis(acetonhrile)dichloropaIladium at a temperature between 50 and !50'°C. Suitable solvents include DMF, DMPU, HMPA, DMSO, toluene, and DME. (for examples see Farina, V. Krishnamurthy, V.; Scon, WJ. Organic Reactions, 1997,50, 1). Reduction of the olefin using, for example, Wilkinson's catalyst in a solvent such as toluene, THF or an alcohol at a temperature between about 20 and SO °C provides the corresponding alkane linked system. In certain heterocyclic systems in which a bromide or chloride is situated ortho or para to a ring nitrogen, the halogen can be readily displaced by an alcohol (in the presence of base such as sodium hydride in a solvent such as Toluene, DMSO, THF, DMPU or HMPA) at or above room temperature (For examples see Kelly, T.R. et al. J. Amer. Chem. Soc, 1994,116, 3657 and Newcome, G.R. et al J. Org. Chem., 1977, 42, 1500). For example, alcoholysis of a 2,4-dichloro-pyrimidine (Scheme 50) using a controlled stoichiometric amount of an alcohol reagent containing Arl (or Arill) provides the aJkoxy substituted-bromo-pyrimidine. Subsequent reaction of this product (generally above room temperature) with a further equivalent of another alcohol containing Arill (or Arl) provides the unsymmetricatly dialkoxy-substituted heterocycle. Since the 4-position of the dichloro-pyrirnidine is generally displaced first, the order in which the alkoxy substituents are introduced will dictate their orientation in the product. Similar procedures using 2,6-dibromc-pyridine or 2,6-dibromo-pyridazine provides the corresponding dialkoxy-substituted pyridines and pyridazines. A simple alkoxy group positioned ortho to a nitrogen in these heterocyclic systems can be hydrolyzed to the corresponding hydroxy substituent using aqueous hydrochloric acid at a temperature normally between room temperature and reflux. (Scheme 51). For example (Scheme 5 \\ treatment of the 2-methaxy-6-alkyl-substituted pyridine derivative with hydrochloric acid provides the 6-alkyl substituted pyridin-2-one. This intermediate, in turn, can be further derivatized to the corresponding 2-aIkoxy or 2-aIkenyl substituted systems as detailed elsewhere in die sdescription of this invention. A methyl, methylene or methine group positioned ortho to a ring nitrogen in these heterocyclic systems can be deprotonated widi a base such as an alkyl lithium or LDA in a solvent such as THF, emer or HMPA, generally at low temperature (below 0°C) and the resulting anion reacted with electrophiles such as aldehydes, epoxides, alkyl halides or a,pVunsaturaied carbonyl compounds to provide a variety of functionalized heterocycles. Scheme 52 For example (Scheme 52) the 2-aIkoxy-4-methyl-pyrimidine is treated, sequentially, with LDA and an aldehyde at -78 °C to" give the hydroxy substituted adduct. Subsequent dehydration of this intermediate with martin sulfurane in a solvent such as dichloromethane.at ambient temperature followed by hydrogenation of the resulting olefin provides the 4-ArI-containing-aIkyl-2-alkoxy-pyrimidme. Similar procedures applied to 2-chIoro-6-methyl-pyrazine (Karmas, G.; Spoerri, P.E.; J. Amer. Chem. Soc. 1952, 74, 1580) leads to the corresponding pyrazine. In another embodiment of this invention, A can be an amide thus generating compounds of the formulas shown in Figure 9. Figure 9 The preparation of an illustrative example within this series is shown in scheme 53. A hydroxy aldehyde can be reacted with a bromoalkyl-ester to provide an aldehyde-ester intermediate. Reductive amination of the aldehyde followed by acylation can provide the amide. Furthermore, compounds of the invention may be easily synthesized by solid phase methods, as illustrated in Schemes 54 and 55, using inputs (XII) - (XVII) listed in Table 1. An additional exemplification of the amide linker is shown in Scheme 56. Reaction of an activated carboxylic acid derivative such as, but not limited to, an acid chloride or anhydride with an amine of genera) formula (15) and a suitable base such as triethylamine provides the amide {16). More explicit exemplification is shown in Scheme 57. Carboxylic acid (17) is activated widi oxafyl chloride to provide the acid chloride and then 2-amino-6-methylbenzoic acid (IS), is added to provide the amide (19). Alternatively, 2-aminom ethyl-6-methylbenzoic acid (20) can be used to provide the amide (21). The preparation of 2-aminom ethyl-6-methylbenzoic acid, (20), can be accomplished using the chemistry shown in Scheme 31 (X = Me, R' = H). Compounds useful according to the invention may also be prepared by the application or adaptation of known methods, by which is meant methods used heretofore or described in the literature, for example those described by R. C. Larock in Comprehensive Organic Transformations. VCH publishers, 1989. In the reactions described hereinafter, it may be necessary to protect reactive functional groups, for example hydroxy, amino, imino, thio or carboxy groups, where these are desired in the final product, to avoid their unwanted participation in the reactions. Conventional protecting groups may be used in accordance with standard practice, for examples see T.W. Green and P.G.M.Wuts in "Protective Groups in Organic Chemistry" John Wiley and Sons, 1991; J. F. W. McOmie in "Protective Groups in Organic Chemistry" Plenum Press, 1973. According to a further feature of the present invention, compounds useful according to the invention may be prepared by interconversion of other compounds of the invention. A compound of the invention including a group containing one or more nitrogen ring atoms, preferably imine (=N-), may be converted to the corresponding compound wherein one or more nitrogen ring atom of the group is oxidized to an N-oxide, preferably by reacting with a peracid, for example peracetic acid in acetic acid or m-chloroperoxybenzoic acid in an inert solvent such as dichloromethane, at a temperature from about room temperature to reflux, preferably at elevated temperature. The products of this invention may be obtained as racemic mixtures of their dextro and levorotatory isomers since at least one asymmetric carbon atom may be present. When two asymmetric carbon atoms are present, the product may exist as a mixtures of diastereomers based on syn and anti configurations. These diastereomers may be separated by fractional crystallization. Each diastereomer may then be resolved into dextro and levorotatory optical isomers by conventional methods. It will also be apparent to those skilled in the art that certain compounds of Formula I may exhibit geometrical isomerism. Geometrical isomers include the cis and trans forms of compounds of the invention having an alkenyl moiety. The present invention comprises the individual geometrical isomers and stereoisomers and mixtures thereof. Such isomers can be separated from their mixtures, by the application or adaptation of known methods, for example chromatographic techniques and recrystallization techniques, or they are separately prepared from the appropriate isomers of their intermediates, for example by the application or adaptation of memods described herein. Resolution may best be carried out in the intermediate stage where it is convenient to combine the racemic compound with an optically active compound by salt formation, ester formation, or amide formation to form two diasteromeric products. If an acid is added to an optically active base, then two diastereomeric salts are produced which possesses different properties and different solubilities and can be separated by fractional crystallization. When the salts have been completely separated by repeated crystallization, the base is split off by acid hydrolysis and enantiomericaliy purified acids are obtained. Compounds useful according to the invention are useful in the form of the free base or acid or in the form of a pharmaceutical hy acceptable salt thereof. Ail forms are within the scope of the invention. Where a compound useful according to the invention is substituted with a basic moiety, acid addition salts are formed and are simply a more convenient form for use; in practice, use of the salt form inherently amounts to use of the free base form. The acids which can be used to prepare the acid addition salts include preferably those which produce, when combined with the free base, pharmaceutically acceptable salts, that is, salts whose anions are non-toxic to the patient in pharmaceutical doses of the sale, so that the beneficial pharmaceutical effects of these compounds in the free base are not vitiated by side effects ascribable to the anions. Although pharmaceutically acceptable salts of said basic compounds are preferred, all acid addition salts are useful as sources of the free base form even if the particular salt, per se, is desired only as an intermediate product as, for example, when the salt is formed only for purposes of purification, and identification, or when it is used as an intermediate in preparing a pharmaceutically acceptable salt by ion exchange procedures. Pharmaceutically acceptable salts useful within the scope of the invention are those derived from the following acids: mineral acids such as hydrochloric acid, trifiuoroacetic acid, sulfuric acid, phosphoric acid and sulfamic acid; and organic acids such as acetic acid, citric acid, lactic acid, tartaric acid, malonic acid, methanesufonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, cyclohexylsulfamic acid, quinic acid, and the like. The corresponding acid addition salts comprise the following: hydrohalides, e.g. hydrochloride and hydrobromide, trifluoroacetate, sulfate, phosphate, nitrate, sulfamate, acetate, citrate, lactate, tartarate, malonate, oxalate, salicylate, propionate, succinate, fumarate, maleate, methylene-bis-p-hydroxynaphthoates, gentisates, mesylates, isothionates, di-p-toluoyltartrates, methanesulfonaies, ethanesulfonates, benzenesulfonates, p-toluenesulfonates, cyclohexylsulfamate and quinate, respectively. The acid addition salts of the compounds useful according to the invention are prepared by reaction of the free base with the appropriate acid, by the application or adaptation of known methods. For example, the acid addition salts of the compounds of this invention are prepared either by dissolving the free base in aqueous or aqueous-alcohol solution or other suitable solvents containing the appropriate acid and isolating the salt by evaporating the solution, or by reacting the free base and acid in an orsanic solvent, in which case the salt separates directly or can be obtained by concentration of the solution. The compounds useful according to the invention may be regenerated from the acid addition'salts by the application or adaptation of known methods. For example, parent compounds useful according to the invention can be regenerated from their acid addition salts by treatment with an alkali, e.g., aqueous sodium bicarbonate solution or aqueous ammonia solution. Where the compound useful according to the invention is substituted with an acidic moiety, base addition salts may be formed and are simply a more convenient form for use; in practice, use of the salt form inherently amounts to use of the free acid form. The bases which can be used to prepare the base addition salts include preferably those which produce, when combined with the free acid, pharmaceutically acceptable salts, that is, salts whose cations are non-toxic to the animal organism in pharmaceutical doses of the salts, so that the beneficial pharmaceutical effects onthe activity of the compounds of die present invention in the free acid are not vitiated by side effects ascribable to the cations. Pharmaceutically acceptable salts useful according to the invention, include for example alkali and alkaline earth metal salts, including those derived from the following bases: sodium hydride, sodium hydroxide, potassium hydroxide, calcium hydroxide, aluminum hydroxide, lithium hydroxide, magnesium hydroxide, zinc hydroxide, ammonia, ethylenediamine, N-methyl-glucamine, lysine, arginine, ornithine, choline, N,N%3ibenzyiethylenediamine, chJoroprocaine, diethanolamine, procaine, diethylamine, N-benzylphenediylamine, piperazine, tris(hydroxymethy!)aminomethane, tetramethylammonium hydroxide, and the like. Metal salts of compounds useful according to the present invention may be obtained by contacting a hydride, hydroxide, carbonate or similar reactive compound of the chosen metal in an aqueous or organic solvent with the free acid form of the compound. The aqueous solvent employed may be water or it may be a mixture of water with an organic solvent, preferably an alcohol such as methanol or ethanol, a ketone such as acetone, an aliphatic ether such as tetrahydrofuran, or an ester such as ethyl acetate. Such reactions are normally conducted at ambient temperature but they may, if desired, be conducted with heating. Amine salts of compounds useful according to the present invention may be obtained by contacting an amine in an aqueous or organic solvent with the free acid form of the compound. Suitable aqueous solvents include water and mixtures of water with alcohols such as methanol or ethanol. ethers such as tetrahydrofuran- nitriles such as acetonitrile, or keiones such as acetone. Amino acid salts may be similarly prepared. The base addition salts of the compounds useful according to the invention can be regenerated from the salts by the application or adaptation of known methods. For example, parent compounds useful according to the invention can be regenerated from their base addition salts by treatment with an acid^ e.g. hydrochloric acid. Salt forms useful according to the invention also include compounds having a quariemarized nitrogen. The quarternarized salts are formed by methods such as by alkyiation of sp"* or sp hybridized nitrogen in the compounds. As will be seif-evident to those skilled in the art, some of the compounds useful according to the invention do not form stable salts. However, acid addition salts are most likely to be formed by compounds useful according to the invention having a nitrogen-containing heteroaryl group and/or wherein the compounds contain an amino group as a substituent Preferable acid addition salts of the compounds useful according to the invention are those wherein there is not an acid labile group. As well as being useful in themselves as active compounds, the salts of the compounds useful according to the invention are useful for the purposes of purification of the compounds, for example oy exploitation of the solubility differences between the salts and the parent compounds, side products and/or starting materials by techniques well known to those skilled in the art. . Various substituents on the compounds useful according to the invention, e.g_, as defined in R, R| and Ri can be present in the starting compounds, added to any one of die intermediates or added after formation of the final products by known methods of substitution or conversion reactions. If the substituents themselves are reactive, then the substituents can themselves be protected according to the techniques known in the art. A variety of protecting groups known in the art may be employed. Examples of many of these possible groups may be found in "Protective Groups in Organic Synthesis" by T. W. Green, John Wiley and Sons, 1981. For example, nitro groups can be added to the aromatic ring by nitration, and the nitro group then converted to other groups, such as amino, by reduction, and halo, by diazotization of the amino group and replacement of the diazo group. Acyl groups can be substituted onto the aryl groups by Friedel-Crafts acyiation. The acyl groups then can be transformed to the corresponding alkyl groups by various methods, including the Wolff-Kishner reduction and Clemmenson reduction. Amino groups can be alkylated to form mono and dialkyiamino groups; and mercapto and hydroxy groups can be alkylated to form corresponding ethers. Primary alcohols can be oxidized by oxidizing agents known in the art to form earboxylic acids or aldehydes, and secondary alcohols can be oxidized to form ketones. Thus, substitution or alteration reactions can be employed to provide a variety of substituents throughout the molecule of the starring material, intermediates, or the final product. The starting materials, intermediates and some compounds of the invention are prepared by tHe application or adaptation of known methods, for example methods as described in US Patent No.s 4,920,132; 4,920,131; and 5,059,610; publications Huang, Fu Chin et al, J. Med. Chem. (1991), 34(5), 1704-7; and Huang, Fu Chih et al, J.Med. Chem. (1990), 33(4), 1194-200; and the Reference Examples or their obvious chemical equivalents. The present invention is further exemplified but not limited by the following examples, which illustrate the preparation of the compounds according to the invention. Example 1 Methvl 2.6-dimethvl-ben2oaie To a cooled (0 °C) solution of 2,6-dimethylbenzoic acid (20.2g, 134 mmol) in dicbloromethane (200 mL) is added DMF (1 mL) followed by oxalyl chloride (14 mL, 162 mmol). On completionof addition, the cold bath is removed and stirring continued for 3b, The resulting solution is concentrated under vacuum and the residue added slowly to a cooled (0 °C) solution comprising methanol (200 mL) and triethylamine (40 mL). On completion of addition, the reaction mixture is stirred for 30 rain, then poured into hydrochloric acid solution (400 mL, 2N) which is then extracted with ether. The ether extract is washed with hydrochloric acid solution (IN), sodium bicarbonate solution and brine then dried over MgS04 and concentrated to give the title compound which is used without further purification. MS (EI) 164 (M)+. Example 2 Methvl 2-bromomethyl-6-rnethvl-benzoate To a solution of methyl 2,6-dimethyl-benzoate (22.0 g , 134 mmol, example 1) in CCLj (250 mL) is added W-bromo-succinimide (19g, 107 mmol) followed by benzoyl peroxide (1.0 g, 4.0 mmol). The resulting solution is wanned to reflux and stirred at this temperature for 20 min. The reaction mixture is then allowed to cool before being diluted with ether (200 mL), filtered and concentrated. The residue is purified by flash chromatography (silica, 4% acetone in hexanes) to give the title compound. This product (approx. 85% purity, remainder is methyl 2,6dimethyl benzoate) is used without further purification. MS (EI) 242, 244 (M*, Br pattern). Example 3 3-(Quinolin-2-vlmethoxy)-phenoI 2-ChIoromethylquinoline hydrochloride (25.0 g, 117 mmol) and resorcinol monobenzoate (37.5 g, 175 mmol) are suspended in dimethylsulfoxide (180 mL) and are mixed with the aid of an overhead stirrer. The mixture is cooled to 15 °C and a 50% solution of sodium hydroxide (25 mL) is added slowly over 10 min with a slight exotherm. The reaction is allowed to come to room temperature and is allowed to stir overnight. The reaction is then heated to 95 °C and a 50% solution of sodium hydroxide (25 mL) is added over 10 min. After 20 min. hot water (300 mL) is added to the reaction and stirred 15 min. The reaction is hot filtered and the filtrate is cooied to provide a brick red solid which is dried in vacuo to provide the sodium salt pentahydrate. A portion of the salt (15.6 g, 43.0 mmol) is neutralized by hearing in water (30 mL) with IN HC1 (43 mL) followed by cooling to provide a brown solid. The solid is dissolved in dichloromethane (550 mL) and methanol (14 mL), dried over magnesium sulfate, filtered and concentrated in vacuo to yield the title compound as a tan solid. A portion is recrystallized from ethyl acetate to provide an analytically pure sample; m.p. 152-153 °C, MS (ESI) 252 (M+H)+. Example 4 Methyl 2-methvl-6-r3-fquinolin-2-ylmethoxv)-phenoxvmethvl1-benzoate 3-(Quinolin-2-ylmethoxy)-phenol (5.2 g, 21 mmol, example 3), methyl 2-bromomethyI-6-metbyl-benzoate (example 2) (5.0 g, 21 mmol) and potassium carbonate (4.4 g, 32 mmol) are combined in DMF (50 mL) and heated at 85 °C for 3h. The reaction is poured into ethyl acetate (500 mL) and washed with water (4 x 120 mL) and brine (100 mL). The solution is dried over magnesium sulfate, filtered and concentrated in vacuo to provide a residue which is purified by column chromatography (silica, 10 to 20% ethyl acetate in hexane) to provide the title compound. MS (ESI) 414 (M+H)+. The following compounds are prepared using essentially the same procedure used in example 4 except using the cited phenol in place of 3-(quinolin-2-ylmethoxy)-phenoI with either the methyl Dr isobutyl benzoate (example 2). Example 4a Methvl {2-memyl-6H3-f2-quJnoIin-2-vl-vinyl)-phenoxvmethvfl|-benzoate. MS (ESI) 410 (M+H)+. Prepared from 3-(2-quinoIin-2-yl-vinyl)-phenol (example 15). Example 4b Methvl (2-Methvl-6-j3-|"2-(pvridin-2-vloxvVethoxv"i-phenoxvmethvl)Vbenzoate 'HNMR(300MHz,CDCl3)5 8.15(m, lH),7.60(t, 1H), 7.1-7.38 (m,4H), 6.89 (dd, 1H),6.81 (d, 1H), 6.56 (m, 3H), 5.08 (s, 2H), 4.70 (t, 2H), 4.32 (t, 2H), 3.85 (s, 3H), 2.36 (s, 3H). Prepared from 3-[2-(pyridin-2-yIoxy)-ethoxy]-phenol (example 15a). Example 4c Methyl 2-[3-ffBenzoxazol-2-vl-methyl-aminoVmethvl1-phenoxymethvl|-6-methvl-benzoate MS (ESI) 417 (M+H)+. Prepared from 3-[(N-benzoxazol-2-yl-N-methyl-amino)-methyl]-phenol (example 10a). Example 4d Methyl 2-rnethvl-6-{3-r(methyl-quinolin-2-yl-amino)-methvn-phenoxymethvl)-benzoate MS (ESI) 427 (M+H)+. Prepared from 3-[(N-methyl-N-quinolin-2-yl-amino)-methyl]-phenol (example 10b). Example 4e Isobutyl 2-methyl-6-r3-fquinoUn-2-yloxymethvl)-phenoxvmethvIl-benzoate MS (ESI) 456 (M+H)+. Prepared from 3-(quinolin-2-yloxymethyl)-phenoI (example 15b). Example 4f Methyl 2- {3-r2-(5-ethvl-pvTidin-2-vl)-ethoxv1-pheDoxymethyl)-6-methyl-ben2oate 'HNMR (300 MHz, CDC13) 5 8.39 (bs, 1H), 7.46 (d, 1H), 7.28 (m, 2H), 7.16 (m, 3H), 6.52 (m, 3H), 5.06 (s, 2H), 4.31 (t, 2H), 3.82 (s, 3H), 3.22 (t, 2H), 2.63 (q, 2H), 2.38 (5, 3H), 1.24 (t, 3H). MS (ESI) 406 (M+H)+. Prepared from 3-[2-(5-ethyl-pyridin-2-yl>ethoxy]-phenol (example 71). Example 4g Methvl 2-methvl-6-f3-(2-pvridin-2-vl-ethoxy)-phenoxymethyn-benzoate lH NMR (300 MHz, CDC13) 5 8.56 (d, 1H), 7.62 (m, 1H), 7.28 (m, 2H), 7.16 (m, 3H), 6.52 (m, 4H), 5.06 (s, 2H), 4.34 (t, 2H), 3.82 (s, 3H), 3.25 (t, 2H), 2.38 (s, 3H). MS (ESI) 378 (M+Hf. Prepared from 3-(2-pyridin-2-yl-ethoxy)-phenol (example 71a). Example 4h Methyl 2-r3-rBenzooxazoI-2-vlaminomethvlVphenoxvmethvl1-6-methvI-benzoate 'H NMR (300 MHz, CDC13) S 7.54 (m, 1H), 7.38 (d, 1H), 7.26 (m, 3H), 7.18 (m, 2H), 7.05 (m, 1H), 6.98 (m, 2H), 6.88 (dd, 1H), 5.10 (s, 2H), 4.64 (bs, 2H), 3.80 (s, 3H), 2.37 (s, 3H). MS (ESI) 403 (M+H)". Prepared from 3-(berizooxazol-2-ylarriinomethyI}-phenol (example 10c). Example 4i Methyl 2-methvl-6-r3-(pvridin-2-vlmethoxvmethvl)-phenoxvmethvn-benzoate 'H NMR (300 MHz, CDC13) 6 8.56 (d, 1H), 7.71 (m, 1H), 7.48 (d, 1H), 7.25 (m, 5H), 6.99 (m, 2H), 6.87 (dd, 1H), 5.11 (s, 2H), 4.69 (s, 2H), 4.63 (s, 2H), 3.82 (s, 3H), 2.38 (s, 3H). MS (ESI) 378 (M+H)+. Prepared from 3-(pyridin-2-ylmethoxymethyI)-phenoI (example 74). Example 4j Methyl 2-methyl-6-r3-fquinoHn-2-ylmethoxymethylVphenoxymethyn-benzoate 'H NMR (300 MHz, CDCI3) 6 8.19 (d, 1H), 8.06 (d, 1H), 7.82 (d„ 1H), 7.69 (m, 2H); 7.53 (m, 1H), 724 (m, 4H), 7.01 (m, 2H), 6.88 (dd, 1H), 5.12 (s, 2H), 4.86 (s, 2H), 4.66 (s, 2H), 3.82 (s, 3H), 2.38 (s, 3H). MS (ESI) 428 (M+Hf. Prepared from 3-(qumolin-2-ylmetioxymethyl)-phenol (example 74a). Example 5 Methyl 2-methvl-6-[(3-hvdroxy-phenoxv>-methyn-ben2Qate To a solution of3-hydroxy-phenoI (1.5g, 13.6 mmol) in acetonitrile (50mL) is added methyl 2-(bromomethyl)-6-methyl-benzoate (0.82g, 3.4 mmol, example-2) followed by K2CO3 (3.76g, 27.2 mmol). The resulting mixture is heated to 50 °C and stirred at this temperature for 90 min. then cooled, filtered and the filtrate concentrated under vacuum. The residue is purified by flash chromatography (silica, 5% ethyl acetate in dichloromethane) to give the title compound as a white solid. MS (El) 272 (M~). Example 6 Methvl 2-methvl-6-r3-(2-phenvi-oxazol-4-vlnieihoxv>-phenoxvmelhvl]-benzoate To a solution of 4-chloromethy]-2-phenyI-oxazole (1 OOmg, 0.5 mmol. example 19) in DMF (2 mL) is added methyl 2-methyl-6-[(3-hydroxy-phenoxy)-methyl]-ben2oate (136 mg, 0.5 mmol, example 5) followed by K2CO3 (75 mg, 0.54 mmol). The resulting mixture is heated to 60 °C and stirred at this temperature for 8 h. This mixture is then cooled to room temperature, diluted with ether, washed with water and brine, dried over MgS04 and concentrated. The residue is purified by flash chromatography (silica, 20% ethyl acetate in hexanes) to give the title compound. MS (ESI) 429 (M+H)+. The following compounds are prepared using essentially die same procedure used in Example 6 except using the cited alkyl halide in place of 4-chloromethyl-2-phenyl-oxazole with either methyl (etfryl or isobutyl) 2-methyl-6-[(3-hydroxy-phenoxy)-memyI]-benzoate (example 5). Example 6a Methyl 2-memvl-6-r3-(2-phenvl-thiazol-4-ylmethoxy>-phenoxvmethyl1-benzoate MS (ESI) 446 (M+H)+. Prepared from 4-chloromethyI-2-phenyI-thiazole (example 20). Example 6b Methyl 2-r3-(3.5-dimethyl-isoxazol-4-vlniethoxy)-phenoxvmethyn-6-methvl-benzoate MS (ESI) 382 (M+H)+. Prepared from 3,5-dimethyl-isoxazol-4-ylrnethyl chloride. Example 6c Methvl 2-methvl-6-r3-f5-phenyl-ri.2.41oxadiazol-3-ylmethoxv)-phenoxvmethvll-ben2oate MS (ESI) 431 (M+H)+. Prepared from 5-phenyl-[l,2,4]oxadiazoI-3-yImethyI chloride. Example 6d Methyl 2-r3-f2.5-dimethvl-benzvloxy)-phenoxvmethvn-6-memvl-benzoate MS (ESI) 391 (M+H)+. Prepared from 2,5-dimethvl-benzvI chloride. Example 6e Methyl 2-r3-r2.4-dichioro-benzvloxvVDhenoxvmethvll-6-metfayl-ben2oate MS (ESI) 431 (M+H, Cl2 patternf. Prepared from 2,4-dichloro-benzyi chloride. Example 6f Methyl 2-r3-f5-tert-biityl-('l;2.41oxadia2oI-3-Ylmethoxv)-pheiioxvinethYlV6-methv]-bflrizoate MS (ESI) 411 (M+H)+. Prepared from 5-Kr/-butyl-[;U,4]oxadiazol-3-ylmethyI chloride. Example 6g Methyl 2-{3-f3-(2.6-dichAoro-phenvtV5-methyl-isoxazol-4-ylmethoxvVphenoxymethyU-6- methvl-benzoate MS (ESI) 512 (M+H)+. Prepared from (3-{2,6-dichloro-phenyl)-5-methyl-isoxazoI-4-yI)-methyI chloride. Example 6h Memyl2-methyI-6-r3-(2.4.5-trimethyl-ben2yloxyVphenoxvmethvI]-benzoate MS (ESI) 405 (M+H)+. Prepared from 2,4,5-trimethyI-benzyl chloride. Example 6i Methyl 2-methyl-6*r3-f3-methyI-raphtr^den-2-vlmethoxv>-pheaoxvmethyn-ben2oate MS (ESI) 427 (M+H)+. Prepared from (3-methyl-naphthalen-2-yI)-methyl bromide. Example 6j Methvl2-t3-f5-acetvi--2-methoxv-ben2vloxv)-phenoxvmgthvIl-6-rrie'thyl-benzoate MS (ESI) 435 (M+H)'. Prepared from 5-acetyl-2-methoxy-benzyl chloride. Example 6k Methvl 2-[3-f6-fiuoroquinolin-2-vImethoxv)phgnoxvmethvl1-6-methvifaenzoaie MS (ESI) 432 (M+H)+. Prepared from 6-fiuoroquinolin-2-ylmethyl bromide (example 27b). Example 61 Methvl 2-!"3-(4-fgr/-butylbenzvloxv)phenoxvmethyI1-6-methylbenzoate MS (ESI) 419 (M+H)+. Prepared from 4-{/er/-butyI)benzyl bromide. Example 6m Methvl 2-f3~(4-isopropvlbenzvloxv)pheDoxvmethvll-6-methvlben2oate MS (ESI) 405 (M+H)+. Prepared from 4-isopropylbenzyl chloride. Example 6n Methyl 2-methvl-6-p-f3-phenoxvbenzvloxv)pheDOXvmethvllbenzoale MS (ESI) 455 (M+H)+. Prepared from 3-phenoxybenzyl chloride. Exampl6o Methyl 2-f3-(4-/gr?-butvlcyclohexvlmethoxv)phenoxymethvll-6-methvlben2oate MS 425 (M+H)+. Prepared from 4-/er/-butylcyclohexylmethyl bromide (example 29a). Example 6p Methvl 2-methyl-6-r3-fQuinoxalin-2-vimethoxv')phenoxvmethvllbenzoate MS 415 (M+H)+. Prepared from quinoxalin-2-ylmethyI chloride (See Chem. Ber. 1987,120, 649-651). Example 6q Methvl 2-methyl-6-r3-f2-methvlbenzvloxv)phenoxvmethyllbenzoate MS 377 (M+H)". Prepared from ct-bromo-o-xylene. Lxample 6r Methyl 2-methvl-6-{3-r2-("5-methvlihiophen-2-vl)-oxa2oI-4- v tmethoxv"iphenoxvmethvl} benzoate MS (ESI) 450 (M+H)+. Prepared from 2-(5-methylthiophen-2-yl)oxazol-4-ylmethyI chloride (example 19a). Example 6s Methyl 2-r3H'2-cvclohexvlQxazol-4-vlmethoxv')phenoxvmethyl1-6-methylben2oate MS (ESI) 436 (M+H)\ Prepared from 2-cyclohexyloxazol-4-yimethyl chloride (example 19b). Example 6t Methyl 2- {342-(3-fluorophenyQoxazol-4-vlinetfaoxvlphenoxymethvU-6-methylbenzoaie MS (ESI) 448 (M+H)+. Prepared from 2-(3-fluorophenyI)oxazol-4-ylmethyI chloride (example 19c), Example 6u Methyl 2-{3-f2-(4-fluoroDhenyI)oxazoi-4-vImethoxy1phenoxymethvl}-6-metfavlben2oate MS (ESI) 448 (M+H)+. Prepared from 2-(4-fluorophenyl)oxazol-4-ylmethyl chloride (example 19d), Example 6v Ethyl 2-f3-l"6-chloropyridin-2-ylmethoxv)phenoxvmethvn-6-methylbenzoate MS (ESI) 412, 414 (M+H)+, CI pattern. Prepared from 2-chloromethyl-6-chloropyridine (example 27c). Example 6w Ethvl 2-methvi-6-r3-f5-methvl-2-phenvtoxa2ol-4-vlmethoxv)Dhenoxvmethvllbenzoate MS (ESI) 458 (M+H)*. Prepared from 4-chIoromethyl-5-methy3-2-phenyloxazoie. Example 6x Methyl 2-(,3-ben2yloxy-phenoxvmethvlV6-methvl-benzoate MS (EI) 362 (M)+- Prepared from benzyl bromide. Example 6y Methyl 2-meihvI-6-[3-(pvridin-2-vlmelhoxy)-phenoxvmethyll-benzoate Prepared from 2-chloromethyl-pyridine. Example 6z Methyl 2-r3-(7-chloroquinQlin-2-ylmethoxy)pbenoxvmethyn-6-methylbenzoate MS (ESI) 447 (M+H)+, CI pattern. Prepared from 7-chioroquinolin-2-ylmethyI bromide (example 46a). Example 6aa Methvl 2-r3-(6-memoxyQuinoIin-2-yIrnethoxv)phenoxYrnethyl1-6-methvlbenzoate MS (ESI) 443 (M+H)+. Prepared from 6-methoxyquinoIin-2-ylmethyI bromide (example 46b). Example 6ab Ethvl 2-r3-f2.4-dtisopropvl-5-methvI-benzyloxy)-pheDOxymethyll-6-methyl-benzoate 'HNMR(300 MHz,CDC13) 5 7.14 (m, 6H), 6.62 (m, 3H), 5.10(s,2H), 5.00 (s,2H), 4.32 (m, 2H), 3.20 (m, 1H), 2.86 (m, 1H), 2.40 (bs, 6H), 1.28 (m, 15H). MS (EI) 484 (M)+. Prepared from 1 -chloromethyl-2,4-diisopropyl-5-methyl-benzene. Example 6ac Eihvl2-T3-f2.4-bis-trtfluoromeiAivl-benzyloKyVphenoxvmethvlV6-rnethvl-benzoate t 'H NMR (300 MHz, CDCI3) 5 7.92 (m, 2H), 7.82 (m, 1H), 7.30 (m, 2H), 7.18 (m, 2H), 6.57 (m, 3H), 5.29 (s. 2H), 5.10 (s, 2H), 4.31 (q, 2H),2.39 (s, 3H), 1.29 (t, 3H). MS (El) 512 (M)+. Prepared from 2,4-bis(trifluoromethyI)benzyI bromide. Example 6ad £thvl2-[3-fbiphenvl-4-vlmethoxv>-phenoxvmethvi"l-6-meihvl-benzoate !H NMR (300 MHz, CDCI3) 5 7.60 (m, 4H), 7.40 (m, 7H), 7.18 (m, 2H), 6.58 (m, 3H), 5.09 (s, 2H), 5.07 (s, 2H), 4.30 (q, 2H), 2.39 (s, 3H), 1.28 (t, 3H). MS (EI) 452 (M)+. Prepared from 4-phenylbenzyl chloride. Example 6ae Ethvl 2-methyl-6-r3-(naphthalen-1 -yimethoxy)-phenoxyrnethyl1-benzoate 'H NMR (300 MHz, CDC13) 6 8.04 (m, 1H), 7.88 (m, 2H), 7.52 (m, 4H), 7.24 (m, 4H), 6.67 (m, 2H), 6.59 (m, 1H), 5.46 (s, 2H), 5.10 (s, 2H), 4.30 (q, 2H), 2.39 (s, 3H), 1.28 (t, 3H). MS (EI) 426 (M)+. Prepared from l-crdoromethyl-naprithalene. Example 6af Methyl 2-["3-(5-ethvl-pyridin-2-ylmethoxv)-phenoxymethyl1-6-methyl-benzoate 'HNMR(300 MHz, CDCW) 5 8.44 (bs, 1H), 7.54 (dd, 1H), 7.42 (d, 1H), 7.32 (m,2H), 7.17 (m, 2H), 6.58 (m, 2H), 5.15 (s, 2H), 5.08 (s, 2H), 3.82 (s, 3H), 2.67 (q, 2H), 2.38 (s, 3H), 1.26 (t, 3H). MS (ESI) 392 (M+H)+. Prepared from 5-ethyl-2-chloromeihyi pyridine (example 68). Example 6ag Methyl 2-r3-(4-ethvl-benzvloxv)-phenoxvmethyn-6-methvl-benzoate 'HNMR (300 MHz, CDC13) 5 7.28 (m, 8H), 6.58 (m, 3H), 5.08 (d, 2H), 5.00 (d, 2H), 3.81 (d, 3H), 2.68 (m,2H), 2.38 (s,3H), 1.24 (m,3H). MS (EI) 390 (M)+. Prepared from 1-chloromethy I -4-ethy I-benzene. Example 6ah Methvi 2-f3-f3-bromo4)enzyloxyyphenoxvmethyll-6-methvl-benzoate 'H NMR (300 MHz, CDCI3) 5 7.58 (s, 1H), 7.44 (d, 1H), 7.25 (m, 6H), 6.57 (m, 3H), 5.08 (s, 2H), 5.00 (s, 2H), 3.81 (s, 3H), 2.38 (s, 3H). MS (EI) 440 (M)+. Prepared from 3-bromoben2y] bromide. Example 6ai Ethvl-2-methvl-6-r3-(qiunonn-2-vlmelhoxy)-phenvlethvnvn-benzoale The tide compound is prepared using essentially the same procedure used in Example 6 except using ethyl 2-(3-hydroxy-phenylemynyl>6-methyI-benzoate (example 15c) in place of methyl 2-methyl-6-[(3-hydroxy-phenoxy)-methyl]-benzoate and 2-chloromethylquinotine in place of 4-chloromethyl-2-phenyl-oxazole. MS (ESI) 422 (M+H)+. Example 6aj Methvl 2-methyl-6-r3-f5-phenylpyridin-2-ylmethoxv)phenoxvmethyIlbenzoate MS(ESI) 440 (M+H)+. Prepared from 5-phenyipyridin-2-yImethyl chloride (example 27g). Example 6ak Methvl 2-r3-(2-chloro-benzvloxy)-phenoxymethyll-6-methyl-benzoate 'H NMR (300MHz, CDCI3) 8 7.55 (m, 1H), 7.40 (m, 1H), 7.30 (m, 4H), 7.20 (m, 2H), 6.60 (m, 3H), 5.14 (s, 2H), 5.09 (s, 2H), 3.82 (s, 3H), 2.38 (s, 3H). MS (EI) 396 (Ivf.), CI pattern. Prepared from 2-chlorobenzyl chloride. Example 6al Methvl 2-r3-(4~chloro-benzvloxy')-phenoxvmethvll-6-methvl-ben2oate !H NMR (300MHz, CDCI3) 5 7.32 (m, 6H), 7.18 (m, 2H), 6.56 (m, 3H), 5.08 (s, 2K), 5.00 (s, 2H), 3.81 (s, 3H), 2.38 (s, 3H). MS (EI) 396 (M+.), CI pattern. Prepared from 4-chlorobenzyl chloride. Example 6am 2-Meihvl-6-r3-G-methvl-quinoxalin-2-vimethoxvVphenoxvmethvll-benzoic acid methvl ester MS (ESI) 429 (M+H)*. Prepared from 2-methyi-3-chloromethylquinoxaline (See Chem. Ber. 1987, 720, 649). Example 6an 2-Methyl-6-r3-(naphthalen-2-vlmethoxvVphenoxvmethvn-benzoic acid methvl ester MS (EI) 412 (M*). Example 7 2-Metfavl-6-r3-(quinoIin-2-ylmethoxv')-phenoxvmethvl1-beii2oic acid A solution of methyl 2-methyl-6-[3-(quiooIin-2-yhnethoxy)-phenoxymethyl]-benzoate (1.6 g, 3,8 mmol, example 4) in ethanol (25 mL) is heated with a ION sodium hydroxide solution (4.0 mL, 40 mmol) at 70 °C for 14 h. The reaction is cooled, neutralized with a 2N HC1 solution (20 mL) and concentrated to remove the ethanol. Ethyl acetate is added and washed with water. The aqueous layer is saturated with sodium chloride and back extracted with ethyl acetate. The organic layers are combined, dried over magnesium sulfate, filtered and concentrated to yield a crude solid. The solid is purified by column chromatography (silica, 5 to 10% methanol in dichloromethane) to provide the title compound. An analytically pure sample is prepared by recystallization from methanol: m.p. 167-168 °C, 'HNMRQOO MHZ, CDC13) S.15(d,2H), 7.80 (d, 1H), 7.71 (t, 1H), 7.61-7.51 (m, 2H), 7.26-7.10 (m, 3H), 7.00 (t, 1H), 6.66 (s, 1H), 6.52 (d, 1H), 6.46 (d, 1H), 5.26 (s, 2H), 5.15 (s, 2H), 2.44 (s, 3H); MS (ESI) 400 (M+Hf. An alternate set of conditions that can be used for the hydrolysis of a benzoate ester is to heat a 0.1 M solution of the ester in THF/methanol (1:1) with 10 equivalents of a sodium hydroxide solution (10 N) at 60 °C for 3 h or until starting material disappears, as monitered by TLC analysis. The following compounds are prepared using essentially the same procedure used in example 7 except using the cited ester in piace of methyl 2-methyl-6-[3-(quinoIin-2-ylmethoxy)- phenoxymethyl]-benzoate. Example 7a 2-MethvI-6-r3- lHNMR (300 MHz, DMSO) d 8.87 (bd, 1H), 8.14-8.36 (m, 4H), 8.00 (t, IH), 7.81 (d, 1H), 7.71 (m, IH), 7.34-7.48 (m, SH), 7.29 (bd, 1H), 7.08 (m, 1H), 5.22 (s, 2H), 2.35 (s, 3H). MS (ESI) 396 (M+H)+. Prepared from methyl {2-methyl-6-f3-(2-quinolin-2-yl-vinyI)-phenoxymethyI]-benzoate (example 4a). Example 7b 2-MethyI-6-f3-r2-fpyridin-2-yloxv>-ethoxy1-phenoxvmethvI>-beri2oicacid !HNMR (300 MHz, DMSO) d 8.17 (d, IH), 7.71 (m, lH),7.22(d, IH), 7.04-7.19 (m,3H), 6.99 (dd, IH), 6.86 (d, IH), 6.55 (m, 3H), 5.13 (s, 2H), 4.53 (bs, 2H), 4.28 (bs, 2HX 2.25 (bs, 3H). MS (ESI) 380 (M+H)\ Prepared from methyl (2-methyl-6-{3-[2~(pyridm-2-yloxy)-ethQxyl-phenoxymethyl})-benzoate (example 4b). Example 7c 2-{3-["(Ben2axazol-2-yl-methvl-arnino)-methylVphenoxvmemyl}-6-methyI-benzoicacid 'H NMR (300 MHz, CDC13) 5 7.27 (bd, IH), 7.07-7.3 (m, 5H), 7.03 (t, IH), 6.80 (m, 3H), 5.10 (bs, 2H), 4.61 (bs, 2H), 3.03 (s, 3H), 2.38 (bs, 3H). MS (ESI) 403 (M+Hf. Prepared from methyl 2- {3-[(benzoxazol-2-yl-meuiyl-aniino)-memyl]-phenoxyniethyl}-6-methyl-benzoate (example 4c). Example 7d 2-Memvl-6-0-[(memvl-Quinolin-2-yl-aminoVmeihvil-phenoxvm£thvU-begzoicacid 'H NMR (300 MHz, CDCh) 6 8.09 (d, IH). 7.74 (d, IH), 7.50 (m, 3H), 7.20 (m, 4H), 6.85 (m, 3H). 6.65 (d, IH), 5.20 (s, 2H). 4.75 (s, 2H), 3.29 (s. 3H), 2.05 (s, 3H). MS (ESI) 413 (M+H)+. Prepared from methyl 2-methy!-6-{3-[(methyI-quinoIin-2-yl-amino)-methyi]-phenoxymethy]}-benzoate (example 4d). Example 7e 2-Methvl-6-f3-f2-phenvl-Qxazol-4-ylmeihoxy)-phenoxvmethvll-benzoic acid lH NMR (300 MHz, DMSO) d 8.30 (s, 1H), 8.00 (m, 2H), 7.55 (m, 3H), 7.30 (m, 2H), 7.22 (m, 2H), 6.66 (m, 2H), 6.60 (d, lH), 5.10 (s, 2H), 5.06 (s, 2K), 2.34 (s, 3H). MS (ESI) 416 (M+H)+. Prepared from methyl 2-methyl-6-[3-(2-phenyi-oxa2oI-4-ybnethoxy)-phenoxymelhyl]-benzoate (example 6). Example 7f 2-Methvl-6-[3-f2-phenyl-thiazol-4-ylmethoxv)-phenoxYmethvIl-benzoic acid lHNMR (300 MHz, CDC13) 5 7.95 (m, 2H), 7.43 (m, 3H), 7.32 (m, 2H), 7.24 (d, IK), 7.20 (m, 1H), 7.14 (t, IK), 6.66 (m, 1H), 6.56 (m, IK), 5.20 (s, 2H), 5.15 (s, 2K), 2.41 (s, 3H). MS (ESI) 432 (M+H)+. Prepared from methyl 2-methyI-6-[3-(2-phenyl-thiazol-4-yImethoxy)-phenoxymethyl]-benzoate (example 6a). Example 7g 2-r3-(3.5-Dimethvl-isoxazoI-4-ylmethoxy)-phenQxymethyll-6-methvl-benzoicacid "HNMR (300MHz, CDC13) 6 7.34 (m, 2H), 7.20 (m, 1H), 7.15 (t, 1H), 6.56 (m, 3H), 5.19 (s, 2H), 4.71 (s, 2H), 2.43 (s, 3H), 2.34 (s, 3K), 2.22 (s, 3H). MS (ESI) 368 (M+H)+. Prepared from memyl2-[3-(3,5Hiimetiiyl-isoxa2Bl^ylinethoxy)-phenoxymethyl]-6-methyl-benzoate (example 6b). Example 7h 2-Methyl-6-f3-f5-phenvl-ri.2.41oxadiazol-3-vlmethoxv)-phenoxvmethyI1-benzpicacid lHNMR (300 MHz, CDCb) 68.15 (m, 2H), 7.59 (m, 1H), 7.50 (m, 2K), 7.33 (m, 2H), 7.20 (m, 1H), 7.14 (t, 1H), 6.70 (m, IH), 6.61 (m, 2H), 5.19 (s, 2H), 2.44 (s, 3H). MS (ESI) 417 (M+Hf. Prepared from methyl 2-methyl-6-[3-(5-phenyi-[l ,2,4]oxadiazoI-3-ylmethoxy)-phenoxymeihyl]-benzoate (example 6c). Example 7i 2-F3-f2.5-Dimethvl-benzvloxv)-phenoxvmethyn-6-methvl-benzoic acid 'H NMR (300 MHz, CDC13) 5 7.35 (m, 2H), 7.13-7.24 (m, 3H), 7.09 (d, 1H), 7.04 (A 1H), 6.60 (m, 3H), 5.17 (s, 2H), 4.90 (s, 2H), 2.44 (s, 3H), 2.30 (s, 3H), 2.26 (s, 3H). MS (ESI) 375 (M-H)". Prepared from methyl 2-[3-(2,5-dimethyI-benzyloxy>phenoxymethyl}-6- methyl-benzoate (example 6d). Example 7j 2-f3^2,4-Dichloro-bgnzyloxvVphenoxymethvil-6-methvl-bemTOicacid 'H NMR (300 MHz, CDC13) 5 7.40 (m, 2H), 7.34 (m, 2H), 7.24 (m, 2H), 7.17 (t, 1H), 6.59 (m, 3H), 5.19 (s, 2H), 5.03 (s, 2H), 2.45 (s, 3H). MS (ESI) 415 (M-H, CI2 pattern)". Prepared from memyI2-[3-(2,4-dichloro-benzyloxy)-pbenoxymethyl]-6-methyl-benzoate (example 6e). Example 7k 2-r3-(5-/er/-Butvl-[I.2,41oxadiazol-3-vlmethoxy)-phenoxvmemvl1-6-methyl-benzoicacid 'HNMRQOOMHz, CDC13) 8 7.32 (m, 2H), 7.19 (m, 1H), 7.15 (t, 1H), 6.66 (d, 1H), 6.60 (d, 1HX 6.59 (d, 1H), 5.17 (s, 2H), 5.10 (s, 2H), 1.45 (s, 9H). MS (ESI) 395 (M-H)". Prepared from memyl2-[3 (example 6f). Example 71 2-D43-f2.6-Dichlon>phenvIV5-methvl-isoxazol-4-vlmethoxvl-phenoxyrnethvU-6--methv]-benzoic acid 'H NMR (300 MHz, CDC13) 5 7.24-7.41 (m, 5H), 7.21 (m, 1H), 7.08 (t, 1H), 6.53 (m, 1H), 6.40 (m, 2H), 5.11 (s, 2H), 4.65 (s, 2H), 2.48 (s, 3H), 2.41 (s, 3H). MS (ESI) 496 (M-H)". Prepared from methyl 2-{3-p-(2.6-dichloro-pheny0-5-msthyl-isoxa2o]-4-ylmethoxy]-phenoxymethyl}-6-methyl-benzoate (example 6g). Example 7m 2-Methvl-6-[3-f2.4.,5-trimethvl-benzvloxy)-phenoxvmethvll-benzoic acid 'H NMR (300 MHz, CDCI3) 5 7.35 (m, 2H), 7.20 (m, IH), 7.15 (t, IH), 7.10 (s, IH), 6.97 (s, IH), 6.60 (m, 3H), 5.16 (s, 2H), 4.87 (s, 2H), 2.42 (s, 3H), 2.25 (s, 3H), 2.21 (s, 3H), 2.20 (s, 3H). MS (ESI) 389 (M-H)*. Prepared from methyl 2-methyl-6-[3-(2,4,5-trimethyl-ben2yloxy>-phenoxymethylj-benzoate (example 6h). Example 7n 2-Methyl-6-r3-(3-melhyl-naphthalen-2-ylmethoxv")-phenoxvroetfayn-benzoicacid 'HNMR (300 MHz, CDCI3) 5 7.77 (m, 3H), 7.64 (s, IH), 7.41 (m, 2H), 7.33 (m, 2H), 7.19 (m, 2H), 6.61 (m, 3H), 5.17 (s, 2H), 5.09 (s, 2H), 2.47 (s, 3H), 2.43 (s, 3H). MS (ESI) 411 (M-H)". Prepared from methyl 2-methyI-6-[3-(3-methyl-naphthalen-2- ylmethoxy)-phenoxymethyl]-benzoate(example 61). Example 7o 2-f3-(5-Acetyl-2-methoxv-benzvloxvVphenoxvmethvn-6-methyl-benzoicacid. 'HNMR (300MHz, CDCb) 5 8.05 (bs, IH), 7.93 (bd, IH), 7.33 (m, 2H), 7.20 (m, IH), 7.13 (t, IH), 6.91 (d, IH), 6.60 (m, 3H), 5.16 (s, 2H), 5-03 (s, 2H), 3.89 (s, 3H), 2.53 (s, 3H), 2.43 (s, 3H). MS (ESI) 419 (M-H)". Prepared from methyl 2-[3-(5-acetyl-2-methoxy-benzyloxy> phenoxymethyl]-6-methyl-benzoate (example 6j). Example 7p 2-f3-(6-Fluoroquinolin-2-vlmethoxv">phenQXvmethvl1-6-methvlbenzoicacid m.p. 153-154 °C. 'H NMR (300 MHz, CDCb): 6 8.12 (m, 2H), 7.61 (d, IH), 7.43 (m. 2H), 7.28 (m, 2H), 7.17 (m, IH), 7.05 (m, IH), 6.66 (s, IH). 6.51 (m, 2H), 5.26 (s, 2H), 5.14 (s, 2H). 2.45 (s, 3H). MS (ESI) 418 (M+H)~. Prepared from methyl 2-[3-(6-fIuoroquinoIin-2-ylmethoxy)phenoxymethyi]-6-methylbenzoate (example 6k). Example 7q 2-r3-(4-fgr/-ButvIbenzv]oxY)phenoxvmethvn-6-methvlben2oic acid m.p. 122-123 °C. 'HNMR (300 MHz, CDC13): 5 7.41-7.28 (m, 5H), 7.23-7.12 (m, 3H), 6.61- 6.55 (m, 3H), 5.16 (s, 2H), 4.95 (s, 2H), 2.45 (s, 3H), 1.32 (s, 9H). MS (ESI) 405 (M+H)+. Prepared from methyl 2-[3-(4-/erf-butylbenzyloxy)phenoxyTnethyl]-6-methylbenzoate (example 61). Example 7r 2-T3-f4-Isopropvlbenzvloxv)phenoxvme1hvn-6-metfavlbenzoicacid m.p. 132-133 °C. 'HNMR(300MHz, CDC13): 5 7.35 (m, 5H), 7.22 (m,2H), 7.17(m, 1H), 5.58 (m, 3H), 5.15 (s, 2H), 4.97 (s, 2H), 2.92 (m, 1H), 2.46 (s, 3H), 1.25 (d, 6H). MS (ESI) 391 ^M+H)+. Prepared from methyl 2-[3-(4-isopropyIbenzyIoxy)phenoxymethyl]-6-methylbenzoate ^example 6m). Example 7s Z-Methyi-6-f3-(3-phenoxybenzvloxy)phenoxymethynbenzoic acid H NMR (300 MHz, CDCI3): S 7.31 (m, 5H), 7.15 (m, 1H), 7.12-6.98 (m, 6H), 6.93 (m, 1H), 5.54 (m, 3H), 5.13 (s, 2H), 4.94 (s, 2H), 2.43 (s, 3H). MS (ESI) 441 (M+H)+. Prepared from nethyl 2-methyl-6-[3-(3-phenoxyben2yloxy)phenoxymethyI]benzoate (example 6n). Example 7t ;-[3-(4-/grr-Butvlcvclohexvlmethoxv)phenoxyrnethyl1-6-methvlbenzoicacid 'HNMR (300 MHz, CDCI3): 5 7.34 (m,2H), 7.21 (m, 1H), 7.12 (m, 1H), 6.50 (m, 3H), 5.16 (s, 2H), 3.67 (d, 2H), 2.45 (s, 3H), 1.92-1.75 (m, 4H), 1.64 (m, 2H), 0.98 (m, 4H), 0.84 (s, 9H). MS 411 (M+H)+. Prepared from methyl 2-[3-(4-/£rt-butyicyclohexylmethoxy)phenoxymethyl]-6-methylbenzoate (example 60). Example 7u 2-MethvI-6-r3-("quinoxaIin-2-ylinethoxy)phenoxymethvnfaen2oic acid m.p. 57-60 °C. 'HNMR(300MHz,CDCl3): 5 8.96 (S, 1H), 8.08 (m, 2H), 7.74 (m,2H), 7.24 (m, 2H), 7.12 (m, 1H), 7.00 (m, 1H), 6.64 (s, 1H), 6.49 (m, 2H), 5,24 (s, 2H), 5.14 (s, 2H), 2.39 (s, 3H). MS 401 (M+H)\ Prepared from methyl 2-methyl-6-[3-(quinoxalin-2-ylmethoxy)phenoxymethyl]benzoate (example 6p). Example 7v 2-Methyl-6-r3-|,2-methylbenzvloxy)pfaenoxymethyl1benzoic acid 'H NMR (300 MHz, CDC13): 5 7.35 (m, 3H), 7.20 (m, 5H), 6.59 (m, 3H), 5.17 (s, 2H), 4.95 (s, 2H), 2.44 (5, 3H), 2.32 (s, 3H). MS(APcI) 385 (M+H+Na)+. Prepared from methyl 2-methyl-6-[3-(2-methylbenzyloxy)-phenoxymethyl]benzoate (example 6q). Example 7w 2-Mcthyl-6-{3-f2^5-methvltmophen-2-yl>Qxazol^ylm m.p. 129-130 °C. 'H NMR (300 MHz, CDC13): 5 7.54 (s, 1H), 7.48 (d, 1H), 7.27 (m, 2H), 7.11 (m, 2H), 6.74 (m, 1H), 6.66 (s, 1H), 6.53 (m, 2H), 5.12 (s, 2H)> 4.95 (s, 2H), 2.51 (s, 3H), 2.39 (s, 3H). MS (ESI) 436 (M+H)+. Prepared from methyl 2-methy!-6-{3-[2-(5-methylthiophen-2-yl)-oxa2ol-4-ylmcthoxy]phenoxymethyl}benzoate (example 6r). Example 7x 2-r3-(2-CyclohexylQxa2ol-4-ylmethoxv)phenoxvmethvn-6-methvlben2oicacid m.p. 158-159 °C. >H NMR (300 MHz, CDCI3): 5 7.57 (s, 1H), 7.30 (m, 2H), 7.20 (m, 1H), 7.12 (m, 1H), 6.72 (m, 1H), 6.53 (m, 2H), 5.13 (s, 2H), 4.95 (s, 2H), 2.84 (m, 1H), 2-45 (s, 3H), 2.06 (m, 2H), 1.81 (m, 2H), 1.73-1.20 (m, 6H). Prepared from methyl 2-[3-(2-cyclohexyloxazol-4-ylmethoxy)-phenoxymethyl]-6-methylbenzoate 6s). Example 7y 2-{3-r2-f3~FluorophenvI'>oxazoi-4-vimethoxv]phenoxvmethv3)-6-methvIbenzoicacid m.p. 152-154 °C. 'HNMR(300 MHz, 5:1 CDC33: CD3OD): 5 7.84 (d, 1H), 7.S0 (s, 1H),7.74 (d, 1H), 7.46 (m, 1H), 7.31 (m, 2H), 7.19 (m, 3H), 6.64 (m, 3H), 5.17 (s, 2H), 5.04 (s, 2H), 2.44 (s, 3H). MS (ESI) 434 {M+H)+. Prepared from methyl 2-{3-[2-(3-fluorophenyl)oxazol-4-ylmemoxy]phenoxymethyl}-6-mediylbenzoate (example 6t). Example 7z 2-{3-r2-f4-Fluorophenvl>oxazol-4-vImethoxv1phenoxymethyI)-6-methvlbenzoicacid m.p. 159-160 DC. lHNMR (300 MHz, CDC13): 5 8.03 (m, 2H), 7.70 (s, 1H), 7.32 (d, 2H), 7.16 (m, 3H), 6.93 (m, IH), 6.69 (m, 1H), 6.55 (m, 2H), 5.16 (s, 2H), 5.03 (s, 2H), 2.44 (s, 3H). MS (ESI) 434 (M+H)\ Prepared from methyl 2-{3-[2-{4-fluorophenyl)oxazol-4-ylmethoxy]phenoxymethyI}-6-methylbenzoate (example 6u). Example 7aa 2-f3^6^hloropyridin-2-ylmethoxv)phenoxvmethvn-6-methyIbenzoicacid m.p.97-98°C. 'HNMR(300 MHz, 5:1 CDC13:CD30D): S 7.73 (m, IH), 7.47 (m, IH), 7.28 (m, 3H), 7.16 (m, 2H), 6.60 (m, 3H), 5.16 (s, 2H), 5.12 (s, 2H), 2.42 (s, 3H). MS (ESI) 384, 386 (M+H)*, CI partem. Prepared from ethyl 2-[3-(6-chloropyTidin-2-ylmethoxy)phenoxymethyl]-6-methylbenzoate (example 6v). Example 7ab 2-Memyl-6-[3-(5-methvl-2-pheavloxazol-^ylmethoxy>phenoxYmemYHbenzoicacid m.p, 144-145 DC. 'HNMR (300 MHz, 3:1 CDCI3:CD3OD): 5 7.99 (m, 2H), 7.42 (m, 3H), 7.30 (m, 2H), 7,19 (m, 2H), 6.63 (m, 3H), 5.17 (s, 2H), 4.95 (s, 2H}, 2.45 (s, 3H), 2.43 (s, 3H). MS (ESI) 430 (M+H)+. Prepared from ethyl 2-methyl-6-[3-(5-methyl-2-phenyloxazoI-4-ylmethoxy>-phenoxymethyI]benzoate (example 6w). Example 7ac 2-(3-Ben2ylQxv-phenoxvmethvIV6-methvl-ben2oic acid 'HNMR (300 MHz, CD3OD) d 7.40-7.19 (m. 8H), 7.14 (t, 1H), 6.61-6.51 (m, 3H), 5.07 (s, 2H), 5.03 (s, 2H), 2.40 (s, 3H); MS (EI) 348 (M)+. Prepared from methyl 2-(3-benzyioxy-phenoxymethyi)-6-methyl-benzqaie (example 6x). Example 7ad 2-Methvl-6-f3-fpvridin-2-ylmethoxvVphenoxvmethyn-benzoic acid 'H NMR (300 MHz, CD3OD) d 8.53 (d, 1H), 7.87 (t, 1H), 7.60 (d, 1H), 7.37-7.13 (m, 5H), 6.64-6.59 (m, 3H), 5.15 (d, 4H), 2.40 (s, 3H); MS (ESI) 350 (M+Hf. Prepared from methyl 2-methyl-6-[3-(pyridin-2-ylmethoxy)-phenoxymethyl]-beiizDate (example 6y). Example 7ae 2-r3-f7-Chloroquinolin-2-vlmethoxy)phenoxvmethvll-6-methyl-benzoicacid m.p. 188-193 °C; [HNMR (300 MHz, DMSO-d6) d 8.47 (d, 1H), 8.09 (s, 1H), 8.08 (d, 1H), 7.69 (dd, 2H), 7.29-7.14 (m. 4H), 6.68-6.56 (m, 3H), 5.34 (s, 2H), 5.10 (s, 2H), 2.31 (s, 3H); MS (ESI) 434,436 (M+H;C1)*'. Prepared from methyl 2-[3-{7-chIoroquinolin-2-ylmethoxy)phenoxymethyl]-6-methylbenzQate (example 4bc). Example 7af 2-f3-(6-Methoxvquinolin-2-ylJnethQxy)phenoxymethvn-6-methvIbenzoic acid m.p. 176-179 °C; 'HNMR (300 MHz, DMSO-d*) d 8.29 (d, 1H), 7.91 (d, 1H), 7.60 (d, 1H), 7.42-7.39 (m, 2H), 7.28-7.14 (m, 4H), 6.67-6.55 (m, 3H), 5.27 (s, 2H), 5.09 (s, 2H), 3.90 (s, 3H), 2.31 (s,3H); MS (ESI) 430 (M+H)"". Prepared from methyl 2-[3-(6-methoxyquinoIin-2-ylmethoxy)phenoxyraethyI]-6-methyibenzoate (example 6aa). Example 7ag 2-Mgthv^-6-n-(quinDiin-2-vtoxvmethvU-phepoxvmethvlVbenzoic acid m.p. 68-72 °C; 'HNMR (300 MHz, DMSO-ds) d 8.25 (d, 1H), 7.88 (d, 1H), 7.78 (d, 1H), 7.67 (dd. 1H). 7.43 (dd, 1H), 7.30-7.05 (m, 7H), 6.89 (d. 1H). 5.45 (s, 2H"), 5.11 (s, 2H), 2.30 (s, 3H); MS (ESI) 400 (M+H)". Prepared from isobutyl 2-methyI-6-[3-(quinoIin-2-yIoxymeihy])-phenoxymethyl]-benzoate (example 4e). Example 7ah 2-methvl-6-r3-fauinolin-2-vlmethoxv)-ben2v)o!icvmetrivl1-benzoic Acid m.p. 39-65 °C; lH NMR (300 MHz, CDC13) 58.44 (d, IH), 8.26 (d, 1H), 7.85-7.75 (m, 3H), 7.59 (dd, IH), 7.38 (s, 1H), 7.23 (obs, 2H), 7.15-7.10 (m, 2H), 6.88 (dd, IH), 6.71 (d, 1H), 5.59 (s, 2H), 4.67 (s, 2H), 4.44 (s, 2H), 2.64 (s, 3H); MS (ESI) 414 (M+H)+. Prepared from methyl 2-methyl-6-[3-(quinoIIn-2-ylmethoxy)-benzyloxymethyl3-berizoate (example 53). Example 7ai 2-r3-fOuinoliD-2-ylmethoxy)-benzvloxv1-benzoicacid m.p. 149-154 °C; 'HNMR(300 MHZ, CDC13) 5 8.19 (d, IH), 8.15 (dd, 1H), 8.11 (d, 1H), 7.83 (dd, 1H), 7.77-7.71 (m, 1H), 7.66 (d, 1H), 7.58-7.53 (m, 1H), 7.52-7.46 (m, IH), 7.33 (t, IH), 7.18-7.17 (m, IH), 7.11 (t, 1H), 7.07-7.00 (m, 3H), 5.41 (s, 2H), 5.24 (s, 2H); MS (ESI) 386 (M+H)+. Prepared from methyl 2-[3-(quinoIin-2-yImethoxy)-beiizyloxy]-benzoate (example 60). Example 7aj 3-Memoxy-2-I3-(quinolin-2-ylmethoxy")-benzyloxv)-benzoicacid 'H NMR (300 MHz, CDCI3) 58.20 (d, 1H), 8.10 (d, IH), 7.84 (d, 1H), 7.74 (t, 1H), 7.69-7.65 (m, 2H), 7.56 (t, IH), 7.30 (t, IH), 7.20-7.12 (m, 3H), 7.02 (d, IH), 5.41 (s, 2H), 5.22 (s, 2H), 3.93 (s, 3H); MS(ESI)416(M+H)+. Prepared from methyl 3-methoxy-2-[3-(quinolin-2-ylmethoxy)-benzyloxy]-benzoate (example 60a). Example 7ak 4-Methoxv-2-r3-(quiDolin-2-ylmethoxv)-benzvloxvl-benzoicacid m.p. 117-118 °C; 'HNMR(300 MHz, CDCI3) 58.20 (d, IH), 8.14 (d, IH), 8.09 (d, IH), 7.83 (d. IH), 7.74 (ddd, IH), 7.65 (d, IH), 7.56 (ddd, IH), 7.34 (t, IH), 7.14-7.13 (m, IH), 7.06-7,01 (m, 2H), 6.64 (dd, IH), 6.56 (d, IH), 5.41 (s, 2H), 5.21 (s, 2H), 3.84 (s, 3H); MS (ESI) 416 (M-rfff. Prepared from methyl 4-methoxy-2-[3-(quinoIin-2-ylmeihoxy)-ben2yloxy]-ben2oare (example 60b). Example 7al 5-Methoxv-2-r3-(quinoHn-2-vlmethoxy)-benzvloxy"[-benzoic acid m.p. 24S-249 °C; 'HNMR (300 MHz, DMSO-d6) d 8.40 (d, IH), 8.01 (t, 2H), 7.78 (t, IH), 7.68 (d, IH), 7.61 (t, IH), 7.28-721 (m, 2H), 7.04 (d, IH), 6.94 {dd, IH), 6.78-6.71 (m, 2H), 6.56 (dd, IH), 5.36 (s, 2H), 4.98 (s, 2H), 3.64 (s, 3H); MS (ESI) 416 (M+H)+. Prepared from methyl 5-methoxy-2-[3-(quinoliii-2-ylniethoxy>-benzyloxy}-benzoate (example 60c). Example 7am 2-Methoxy-6-r3-(quinolin-2-ylmethoxy>benzyloxy"l-benzoicacid m.p. 149-152 °C; 'HNMR (300 MHz, CDC13) 58.34 (d, IH), 8.16 (d, IH), 7.80 (d, IH), 7.75 (ddd, IH), 7.69 (d, IH), 7.55 (t, IH), 7.40 (s, IH), 7.27 (t, IH), 7.18 (t, IH), 6.91-87 (m, 2H), 6.60 (d, 2H), 5.45 (s, 2H), 5.08 (s, 2H), 3.89 (s, 3H); MS (ESI) 416 (M+H)+. Prepared from methyl 2-methoxy-6-[3-(quinoiin-2-yimethoxy)-benzyloxy]-benzoate (example 60d). Example 7an 2-Methyl-6-r3-(quinoIin-2-ylniethoxyVbenzvloxy1-benzoicacid m.p.154-156 °C, 'H NMR (300 MHz, CD3OD) d 8.37 (d, IH), 8.05 (d, IH), 7.95 Example 7ao 5-f3-(Quinolin-2-vlmethoxv)-benzvloxy1-nicotimc acid 'HMMR (300 MHz, CDCb) 58.90 (s, IH), 8.52 (s, IH), 8.19 (d, IH), 8.12 (d, IH), 7.87-7.70 (m, 4H), 7.55 (t, IH), 7.30 (t. IH), 7.13 (s, IH), 7.01 (t, 2H), 5.44 (s, 2H), 5.10 (s, 2H); MS (ESI) 3S7 (M+H)+. Prepared from methyl 5-p-(quinolin-2-ylmethoxy)-benzyIoxy]-mcotinate (example 62). Example 7ap 2-r3 Example 7aq 2-r3^2,4-Bis-trifiuorometfayl-benzyloxv)-phenoxymethyn-6-roethYl-benzoicacid !H NMR (300 MHz, CDCh) 6 7.91 (s, 1H), 7.80 (m, 2H), 7.33 (d, 2H), 7.18 (m, 2H), 6.60 (m, 2H), 6.52 (dd, 1H), 5.24 (s, 2H), 5.17 (s, 2H), 2.45 (s, 3H). MS (EI) 484 (M)+. Prepared from ethyl 2-[3-(2,4-bis-trifiuoromemyl-ben2yloxy)-phenoxymethy]]-6-methyl-beiizoate (example 6ac). Example 7ar 2-[3^iphenyl-^vlmethoxy)-phenoxvmethvn-6-niethvl-benzQicacid 'H NMR (300 MHz, CDCh) 5 7.58 (m, 4H), 7.44 (m, 4H), 7.35 (m, 3H), 7.18 (m^H), 6.60 (m, 3H), 5.17 (s, 2H), 5.02 (s, 2H), 2.44 (s, 3H). MS (EI) 424 (M)+. Prepared from ethyl 2-[3-(biphenyl-4-ylmethoxy)-pfaenoxymethyI]-6-methyl-benzoate (example 6ad). Example 7as 2-Methvl-6-D-(naDhthalen-l-vlmethoxv>phenoxvmethyn-ben2oicacid !H NMR (300 MHz, CDCI3) 5 8.00 (m, 1H), 7.85 (m; 2H), 7.47 (m, 4H), 7.34 (m, 2H), 7.17 (m, 2H), 6.62 (m, 3H), 5.40 (s, 2H), 5.16 (s, 2H), 2.43 (s, 3H). MS (EI) 398 (M)T- Prepared from ethyl 2-methyl-6-[3-(naphthalen-l-ylmethoxy)-phenoxymethyI]-ben2oate (example 6ae). Example 7at 2-r3-(5-Ethvl-pvridin-2-vimethoxv)-phenoxvmethy!l-6-methvl-ben2oicacid (H NMR(300 MHz, DMSO) & 8.42 (bs, IH), 7.65 (d, 1H), 7.39 (d, 1H), 6.63 (bs, IH), 6.56 (m, 2H), 2.60 (q, 2H), 2.29 (s, 3H), 1.21 (t, 3H). MS (ESI) 378 (M+H)*. Prepared &om methyl 2-[3-(5-ethyl-pyridin-2-ylmethoxy)-phenoxymethyI]-6-mediyl-benzoate (example 6af). Example 7au 2-f3-f4-Ethvl-benzvloxv)-phenoxymelhyn-6-metfavI-ben2oicacid 5H NMR (300 MHz, DMSO) 5 7.2 (m, 8H), 6.6 (m, 3H), 5.13 (s, 2H), 5.05 (d, 2H), 2.64 (m, 2H), 2.28 (s, 3H), 1.17 (t, 3H). MS (ESI) 375 (M-H)\ Prepared from methyl 2-[3-(4-ethyl-benzyloxy)-phenoxymethyl]-6-methyl-ben2oate (example 6ag). Example 7av 2-f3-(3-Bromo-beTizvloxv)-phenoxvmethyn-6-methyl-benzoicacid 'H NMR (300 MHz, DMSO) 8 7.62 (bs, IH), 7.50 (d, 1H), 7.42 (d, 1H), 7.33 (d, IH), 7.08 (m, 4H), 6.67 (bs, IH), 6.54 (m, 2H), 5.13 (s, 2H), 5.08 (s, 2H), 2.28 Prepared from methyl 2-[3-(3-bromo-benzyloxy)-phenQxymethyl]-6-methyl-benzoate (example 6ah). Example 7aw 2-f3-r2^5~Ethvl-pyridin-2-vl)-ethoxvl-phenoxymethyl>-6-methvl-benzoicacid 'H NMR (300 MHz, DMSO) 8 8.36 (bs, IH), 7.56 (d, IH), 7.14 (m, 5H), 6.49 (m, 3H), 5.11 (bs, 2H), 4.27 (t, 2H), 3.09 (t, 2H), 2.56 (q, 2H), 2.29 (s, 3H), 1.17 (t, 3H). MS (ESI) 392 (M+H)+. Prepared from methyl 2-{3-[2-(5-ethyl-pyridin-2-yi)-ethoxy]-phenoxymethyI}-6-methyl-benzoate (example 4f). Example 7ax 2-MethvI-6-r3-f2-quirioIin-2-vl-ethoxv)-phenoxvmeihvl1-benzoic acid 'H NMR (300 MHA CD3OD) 5 8.2S (d, 1H), 7.97 (d, 1H), 7.88 (d, 1H), 7.74 (t, IH), 7.51 (m, 1H), 7.26 (d, 2H), 7.16 (m, 2H), 7.02 (m, IH), 6.38 (m, 3H), 5.10 (s, 2H), 3.83 (t, 2H), 3.22 (t, 2H), 2.39 (s, 3H). Prepared from methyl 2-methyl-6-[3-(2-quinolin-2-yI-ethoxy)-phenoxymethyl]-benzoate (example 21b). Example 7ay 2-MethvI-6-r3-f2-Dvridin-2-yl-ethoxv)-pheDQxymethyn-benzoicacid 'H NMR (300 MHz, DMSO) 6 8.49 (d, IH), 7.69 (m, IH), 7.26 (m, 3H), 7.04 (m, 2H), 6.38 (m, 4H), 5.03 (s, 2H), 3.67 (t, 2H), 2.94 (t, 2H), 2.31 (s, 3H). MS (ESI) 364 (M+H)+, Prepared from methyl 2-methyl-6-[3-(2-pyridin-2-yl-ethoxy)-phenoxymethyI]~benzoate (example 4g). Example 7az 2-r3-(BenzoQxazol-2-vlaminomethvlVphenoxymethyl1-6-methyl-ben2oic acid 'H NMR (300 MHz, DMSO) 6 8.61 (bt, IH), 7.34 (d, IH), 7.04 (m, 10H), 5.12 (s, 2H), 4.47 (bd, 2H), 229 (3H). MS (ESI) 389 (M+H)+. Prepared from methyl 2-[3-(benzooxazol-2-y!aminomethyI)-phenoxymethyl]-6-methyl-benzoate (example 4h). Example 7ba 2-Methvl-6-r3-CDvridin-2-vlmethoxvmethvIVphenoxymethyn-benzoicacid 'H NMR (300 MHz, DMSO) 5 8.52 (bd, IH), 7.81 (m, IH), 7.47 (d, IH), 7.20 (m, 5H), 6.94 (m, 3H), 5.12 (s, 2H), 4.59 (s, 2H), 4.56 (s, 2H), 2.30 (s, 3H). MS (ESI) 364 (M+H)+. Prepared from methyl 2-methyl^[3^yridin-2-ylmethoxymethyl)-phenoxymethyl]-benzoate (example 4i). Example 7bb 2-Methvl-6-r3-(quinolin-2-ylmethoxvmethvn-phenoxvmethvn-benzoic acid 'HNMR (300 MHz, DMSO) 6 8.40 (d, IH), 7.98 (d, 2H), 7.76 (m, IH), 7.64 (m, IH), 7.31 (m, 5H), 7.00 (m, 2H), 6.92 (dd, IH), 5.12 (s, 2H), 4.79 (s, 2H), 4.62 (s, 2H), 2.32 (s, 3H). MS (ESI) 414 (M+H)+. Prepared from methyl 2-methyl-6-[3-(quinoIin-2-ylmethoxymethyl)- phenoxymethyl]-benzoate (example 4j). / Example 7bc 2-MelhvI-6-{3-r2-(5-metfavI-2-phenvloxazol-4-vIkthoxvlphenoxvmethvUbenzoicacid 'H NMR (300 MHz, CDCI3): 6 8.03 (m, 2H), 7.43 (m, 3H), 7.26 (m, 2H), 7.17 (m, 1H), 7.10 (m, IH), 6.68 (s, 1H), 6.51 (m, 2H), 5.18 (s, 2H), 4.22 (m, 2H), 2.96 (m, 2H), 2.41 (s, 3H), 2.36 (s,3H). MS (ESI) 444 (M+H)+. Prepared from methyl 2-methyl-6-{3-[2-(5-methyl-2-phenyloxa2ol-4-yI)ethoxy]phenoxymethyl}benzoate (example 21a). Example 7bd 2-Melfavl-6-r3-(6-phenylpvridin-2-vlmethoxy")phenoxvmethynbeiizoicacid 'H NMR (300 MHz, CDC13): 5 7.88 (m, 2H), 7.63 (m, IH), 7.52 (m, IH), 7.37 (m, 4H), 7.18 (m, 2H), 6.99 (m, 2H), 6.60-6.36 (m, 3H), 5.14 (s, 2H), 5.00 (s, 2H), 2.23 (s, 3H). MS (ESI) 426 (M+H)+. Prepared from ethyl 2-methyl-6-[3-(6-phenylpyridin-2-yImethoxy)pheno3cymethyI3-benzoate (example 33). Example 7be 2-Methyl-6-r3-fqumolin-2-ylmethoxv)-phenvlsulfanylmethvll-ben2oicacid 'H NMR (300 MHz, DMSO-d*) d 8.40 (d, IH), 7.99 (t, 2H), 7.78 (t, IH), 7.65-7.57 (m, 2H), 7.20-7.01 (m, 6H), 6.85 (t, IH), 5.33 (s, 2H), 4.25 (s, 2H), 2.26 (s, 3H); MS (EST) 415 (M+H)+. Prepared from isobutyl 2-methyl-6-[3-(qumolm-2-ylmemoxy)-phexiylsuli^ylinethyl]-ben2oate_ (example 84). Example 7bf 2-Memvl-6-r3-fqumolin-2-ylmethoxy)-phenvlsiiIfinylmethyn-.benzoicacid [H NMR (300 MHz, DMSO-d6) d 8.43 (d, IH), 8.01 (t, 2H), 7.78 (t, IH), 7.68 (d, IH), 7.62 (t, IH), 7.48 (t, IH), 7.25-7.22 (m, 4H), 7.10 (d, IH), 6.94 (t, IH), 5.41 (s, 2H), 4.22 (d, IH), 4.11 (d, IH), 2.33 (s, 3H); MS (ESI) 432 (M+H)+. Prepared from isobutyl 2-methyl-6-[3-(quinolm-2-ylmethoxy)-phenylsulfmylmethy!]-benzoate (example 85). Example 7bg 2-Methvl-6-r3-(quinolin-2-viinethoxv)-pbenvisuifonvlmethvn-benzoic acid 'H NMR (300 MHz, DMSO-d6)_d 8.43 (d, 1H), 8.05-7.98 (m, 2H), 7.77 (t, 1H), 7.67 (d, 1H),' 7.60 (t, 1H), 7.51 (t, 1H), 7.43-7.35 (m, 2H), 7.26-7.20 (m, 3H), 6.95-6.92 (m, 1H), 5.42 {s, 2H), 4.81 (s, 2H), 2.32 (s, 3H); MS (ESI) 448 (M+H)+. Prepared from isobutyl 2-methyI-6-[3-(quinolm-2-ylmethoxy)-phenyIsu]fonylmethyl]-benzoate (example 86). Example 7bh 2-Methvl-6-r3-(-qimiolin-2-vlmethoxy>-phenvlethvnvn-ben2oicacid 1H NMR (300 MHz, CDC13) d 8.19 (d, 1H), 8.04 (d, 1H), 7.89 (d, 1H), 7.82 (d, 1H), 7.73 (dt, 2H), 7.64 (t, 2H), 7,54 (t, 1H), 7.26 (t, 1H), 6.94 (dd, 1H), 6.81-6.85 (mJ2H)> 5.34 (s, 2H), 2.76 (s, 3H);MS (ESI) 394 (M+H)+. Prepared from ethyl-2-methyl-6-[3-(qiunolin-2-ylmethoxy)-phenylethynyl]-benzoate (example 6ai). Example 7bi 2-Mefeyl-6-[3-f5-TAenvlpyridiD-2-vlmetbflxv)phenoxymethvlTbenzoicacid. mpt &0-83°C. *H NMR (300 mHz, 5:1 CDCbrCE^OD): 5 8.76 (s, 1H), 7.97 (d, 1H), 7.62 (m, 3H), 7.48 (m, 3H), 7.30 (m, 2H), 7.19 (m, 2H), 6.68 (s, 1H), 6.62 (d, 2H), 5.21 (s, 2H), 5.17 (s, 2H), 2.44 (s, 3H). MS(ESI) 426 (M+Hf. Prepared from methyl 2-methyl-6-[3-(5-phenylpyridin-2-ylmethoxy)phenoxymeIhyl]benzoate (example 6aj). Example 7bj 2-r3-(2-Chloro-benzyloxv>-phenoxyn]ethvl1-6-methvl-benzoic.acid 'H NMR (300MHz, DMSO) 5 7.56 (m, 1H), 7.50 (m, 1H), 7.38 (m, 2H), 7.14 (m, 2H), 7.06 (m, 2H), 6.67 (s, 1H), 6.58 (m, 2H), 5.13 (bd, 4H), 2.28 (s, 3H). MS (EI) 382 (M+), CI pattern. Prepared from 2-[3-(2-chloro-benzyloxy)-phenoxymethyl]-6-memyl-benzoate (example 6ak). Example 7bk 2-r3-f4-Chloro-benzvloxv)-Dhenoxvmethvi1-6-meihvl-ben2oic'acid lH NMR (300MHz. DMSO) 5 7.42 (m, 3H), 7.08 (m, 5H), 6.66 (s, 1H), 6.54 (m, 2H), 5.13 (s, 2H), 5.07 (s, 2H), 2.28 (s, 3H). MS (EI) 382 (M".)T CI pattern. Prepared from 2-[3-(4-chloro-benzyIoxy)-phenoxymetf]yI]-6-methyl-benzoate (example 6al). Example 7bl 2-Methvl-6-r3-lr3-methvl-quinoxalin-2-vlmethoxvVphenQxvTngthvl1-benzoicacid 'H NMR (300MHz, DMSO) 5 8.05 (m, 2H), 7.82 (m, 2H), 7.14 (m, 4H), 6.75 (s, 1H), 6.61 (m, 2H), 5.41 (s, 2H), 5.11 (s, 2H), 2.76 (s, 3H), 227 (s, 3H). MS (ESI) 415 (M+Kf. Prepared from 2-Methyl-6-[3-Q-methy!-quinoxaiin-2-yImethoxy)-phenoxyinethyI]-bcnzoic acid methyl ester (example 6am). Example 7bm 2-Methyl-6-l"3-fnaphthalen-2-ylmethoxy>-phenoxvniethvn-benzoicacid 'H NMR (300MHz, DMSO) 6 7.94 (m, 4H), 7.54 (m, 3H), 7.16 (m, 4H), 6.69 (s, 1H), 6.58 (ra, 2H), 574 (s, 2H), 5.11 (s, 2H), 279 (s, 3H). Prepared from 2-Methyl-6-[3-(naphthalen-2-ylmethoxy)- phenoxymethyI]-benzoic acid methyl ester (example 6an). Example 8 3-f(2-Methoxyethoxy)-methoxy1-benzomtrile To a cooled (0 °C) suspension of sodium hydride (840mg, 60% dispersion in mineral oil, 21 mmol) in THF (20 mL) is added a solution comprising 3-hydroxy-benzonitrile (2.4g, 20 mmol), MEM Chloride (2.25 mL, 20 mmol) and DMPU (2 mL) in THF (20 mL). On complete addition, the cold bath is removed and stirring continued for 3h. The reaction mixture is then diluted with ether, washed with water and brine, dried over MgSO* and concentrated. The residue is purified by flash chromatography (silica, 30% ethyl acetate 10 % dichloromethane in hexane) to give the title compound as an oil. MS (ESI) 207 (M+H)+. Example 8a 3-[(2-Methoxvethoxy)-methoxvVbenzaldehvde The title compound is prepared using essentially the same preocedure used in example 8 except using using 3-hydroxy-benzaldehyde in place of 3-hydroxy-benzonitrile. MS (EI) 210 (M)+_ Example 9 3-ff2-Methoxyethoxy)-methoxv1-benzyiamine To a cooled (0°C) solution of 3-[(2-methoxyethoxy)-methoxy]-beri2X)nitrile (3.9g, 18.8 mmol, example 8) in THF (40 mL) is added LAH (40 mL, 1M in THF). The resulting solution is stirred for 10 min. then the cold bath removed and stirring continued for 2 h. The resulting mixture is cooled to 0°C then water (1.5 mL) added dropwise followed by NaOH solution (1.5 mL, 5M) and water (1.5 mL). The resulting suspension is diluted with ether then filtered through celite. The filtrate is concentrated to give the title compound which is used without further purification. MS(ESI)211(M+H)+. Example 10 3-f Quino lin-2-vlaminomethyI)-phenol To a solution of 3-[(2-methoxyethoxy)-methoxy]-benzylamine (422 mg, 2010101, example 9) in DMSO (4 mL) is added 2-chloroquinoline (328 mg, 2 mmol). The resulting solution is warmed to 140 °C and stirred at this temperature for 3h. The resulting mixture is cooled, diluted with water, then extracted with ethyl acetate. The organic extract is washed with brine, dried over MgSC>4 and concentrated. The residue is taken up in methanol (10 mL) then p-toluene sulphonic acid monohydrate (190 mg, 1 mmol) is added. This mixture is wanned to 60 °C and stirred at this temperature for 2h. The reaction mixture is then cooled, concentrated under reduced pressure and the residue purified by flash chromatography (silica, 30% ethyl acetate in dichloromethane) to give the title compound. MS (ESI) 251 (M+H)+. The following compounds are prepared using essentially the same procedure used in example 10 except using the cited chloride and amine in place of 2-chloro-quinoline and 3-[(2-methoxyethoxy)-methoxy]-benzylamine. Example 10a 3-ffN-Benzoxazo 1-2-vI-N-methvi-aTninol-methvll-phenol MS (ESI) 255 (M+H)+. Prepared from 3-[(methylamino)-methyl]-(2-methoxyethoxy-methoxy)-benzene (example 28) and 2-chlero-benzoxazole. Also, omit healing to 140 °C. Reaction stirred at room temperature. Example 10b 3-[(N-Methvl-N-quinolin-2-yl-amino)-methyl1-phenol MS (ESI) 265 (M+H)+. Prepared from 3-[(methyIamino)-methyl]-(2-methoxyethoxy-methoxy)- benzene (example 28) and 2-chloro-quinoline. Example 10c 3-rBenzooxa2ol-2-ylamiDomethvl)-phenol The title compound is prepared using essentially the same procedure used in example 10 except 2-chloro-benzoxazole is used in place of 2-chloro-quinoline. Also, omit heating to 140 °C. Reaction stirred at room temperature. MS (ESI) 241 (M+H)+. Example 11 2-f3-(r2-Methoxvethoxv1-methoxvVphenoxyl)-ethanol To a cooled (0 °C) solution of t-butyl (3-([2-methoxyethoxy]-methoxy)-phenoxy])-acetate (I.2g, 3.8 mmol, example 12) in THF (10 mL) is added a solution of lithium aluminum hydride (5 mL, 1M in THF). The resulting solution is stirred for 10 min. then water (0.2 mL) is added dropwise, followed by NaOH solution (0.2 mL, 5M) and water (0.2 mL). The resulting mixture is diluted with ether, filtered through celite and the filtrate concentrated to give the title compound as an oil which is used without further purification. MS (EI) 242 (M)+. - Example 11a 2-(5-Methvl-2-phenvloxazol-4-vI)ethanol The title compound is prepared using essentially the same procedure used in Example 11 except using methyl 2-(5-methyi-2-phenyloxazol-4-yl)acetate (example 32) in place of t-butyl (3-([2-methoxyethoxy]-methoxy)-phenoxy])-acetate. MS (ESI) 204 (M+H)+. Example 12 /-Butyl (3-(f2-methoxvethoxvl-methoxv)-phenoxyl)-acetate The title compound is prepared using essentially the same procedure used in Example 4 except using 3-([2-methoxyethoxy]-methoxy)-phenol (example 13) in place of 3-{quinolin-2-ylmethoxy)-pbenol and and /-butyl bromoacetate in place of methyl 2-bromomethyl-6-methyl-benzoate. MS (EI) 312 (M)+. Example 13 3-rf2-Methoxyethoxv)-methoxy1-phenol To a cooled (0 °C) suspension of NaH (440 mg, 60% dispersion in oil, 11 mmol) in THF (10 mL) is slowly added a solution comprising 3-benzoyl-phenol (2.14g, 10 mmol), MEM chloride (1.28 mL, 10.5 mmol) and DMPU (3 mL) in THF (20 mL). On complete addition, the cold bath is removed and stirring continued for 2.5 h. Sat. NH4CI solution is added and the mixture diluted with ether, washed with water and brine, dried over MgS04 and concentrated. The residue is taken up in methanol (10 mL) and THF (10 mL) then sodium hydroxide solution (10 mL, 2N) added. This mixture is stirred for 20 min. then hydrochloric acid (10 mL, 2N) added. The mixture is then diluted with ether, washed with sat. NaHCCb solution and brine, dried over MgSC>4 and concentrated. The residue is purified by flash chromatography (silica, 30% ethyl acetate in hexanes) to give the title compound as an oil. 'H NMR (300 MHz, CDC13) 5 7.00 (t, 1H), 6.52 (bd, 1H), 6.48 (bs, 1H), 6.38 (bd, IK), 5.14 (s, 2H), 3.71 (m, 2H), 3.47 (m, 2H), 3.30 (s,3H).. Example 14 K2-Methoxvethoxv)-methoxv1-3-f2-(pvridin-2-vloxv)-ethoxvl-benzene To a solution of 2-(3-([2-methoxyethoxy]-methoxy)-phenoxy])-ethanol (242 mg, 1 mmol, example 11) in DMSO (1.5 mL) is added sodium hydride (44mg, 60% dispersion in mineral oil, 1.1 mmol) followed by 2-fluoro-pyridine (176 mL, 2 mmol). The resulting solution is wanned to 60 °C and stirred at this temperature for 3 h. cooled, diluted with ether, washed with water and brine, dried over MgSCU and concentrated. The residue is purified by flash chromatography (silica, 30% ethyl acetate in hexanes) to give the title compound. MS (ESI) 320 (M+H)+. Example 15 3-f2-OuinoIin-2-vl-vinyn-phenol To a solution of 1^2-meAoxyethoxy)-methoxy-3-(2-quinoIm-2-yl-vinyl)-beiizene (120mg, 0.35 mmol, example 16) is added p-toluene sulphonic acid monohydrate. (74 mg, 039 mmol). The resulting solution is heated to 60 °C and stirred at this temperature for 4 h. The reaction mixture is then cooled, concentrated and the residue taken up in dichloromethane. This solution is washed with sat. NaHCOj solution, dried over MgSC>4 then concentrated to give the title compound as a solid. MS (ESI) 248 (M+H)+. The following compounds are prepared using essentially the same procedure used in example 15 except using the cited MEM ether in place of 1 -(2-methoxyethoxy)-methoxy-3-{2-quinoIin-2-yJ-vinyl)-benzene. Example 15a 3-F2-(pyridin-2-yloxy)-ethoxy'l-phenol MS (ESI) 232 (M+H)+. Prepared from [(2-methoxyemoxy>methoxy]-3-[2-(pyridin-2-yloxy)- ethoxyj-benzene (example 14). Example 15b 3-fQuinolin-2-yloxvmethYl)-phenoI MS (ESI) 252 (M+H)+. Prepared from 2-[3-(2-methoxy-ethoxymethoxy)-benzyloxy]-quinoline (example 81). Example 15c Ethvl2-(3-hvdroxy-phenyleth'ynylV6-meTh^l-benzoatg- MS (EI) 280 (M)+. Prepared from ethyI-2-[3-(2-methoxy-ethoxymethoxy>-pheny]eihynyI]-6-methyl-benzoate (example 98). Example 26 1-C2-Methoxvethoxv)-metho xv-3-(2-quinol in-2-vl-vinyl)-benzene To a cooled (-78 °C) suspension of Iriphenyl-(qumolin-2-yl-melhyI)-phosphonium chloride (1.76g, 4 mmol, example 17) inTHF (24 mL) is added, dropwise, n-butyl lithium solution (1.7 ml, 2.5 M in hexanes). The resulting mixture is stirred for 30 min. then a solution of 3-[(2-methoxyethoxy)-raethoxy]-benzaldehyde (756 mg, 3.6 mmol, example Sa) in THF (3 mL) is added. This mixture is stirred for 30 min then the cold bath removed and stirring continued for 2h. The reaction mixture is then diluted with ethyl acetate, washed with sat ammonium acetate solution and brine, dried over MgSC>4 and concentrated. The residue is purified, by flash chromatography (silica, 40% ethyl acetate in hexanes) to give the title compound as an oil. MS (ESI) 336 (M+H)+. Example 17 Triphenvl-(quinoIin-2-vl-methyl)-phosphonium chloride To a solution of 2-chloromethyl-quinoline (2.9g, 20 mmol) in acetonitrile (32 mL) is added triphenylphosphine (4.49g, 17 mmol). The resulting mixture is warmed to 60 °C and stirred at this temperature for 15 h. This mixture is cooled, diluted with ether, then filtered. The solid is washed with ether, then dried under high vacuum to give the title compound as a solid. 'H NMR (300 MHz, CDC13) 8 8.20 (d, 1H), 8.06 (d, 1H), 7.95 (m, 6H), 7.42-7.8 (m, 13H), 6.10 (d, 2H). Example 18 {2-Methvl-6-f3-(2-quinolin-2-yl-ethvlVDhenoxvmethvl1-pheaoxy)-aceticacid To a solution of {2-methyI-6-[3-(2-quinolin-2-yl-vinyI)-phenoxymethyl]-phenoxy}-acetic acid (94 mg, 0.23 mmol, example 41 a) in DMF (1.5 mL) is added tristriphenylphosphine rhodium chloride (25mg, 0.027 mmol). The resulting solution is placed under an atmosphere of hydrogen, heated to 60 CC and stirred at this temperature for 5h. The reaction mixture is cooled to room temperature and the system is then flushed with nitrogen and concentrated under vacuum. The residue is purified by reverse phase HPLC to give the title compound as a trifjuoroacetate salt. 'H NMR (300 MHz, CDC13) 5 8.57 (d, IH), 8.40 (d, IH), 8.0 (m, 2H), 7.80 (t, IH), 7.52 (d, IH), 7.24 (bd, IH), 7.14 (m, 2H), 7.04 (t, IH), 6.93 (bs, IH), 6.83 (d, IH), 6.74 (d, IH), 5.11 (s, 2H), 4.50 (s, 2H), 3.68 (t, 2H), 3.20 (t, 2H), 2.28 (s, 3H). MS (ESI) 428 (M+H)+. The following compound is prepared using essentially the same procedure used in example 18 except using the cited acid in place of {2-methyl-6-[3-(2-quinolin-2-yl-vinyl)-phenoxymethyl]-phenoxy}-acetic acid. Example 18a 2-Methvl-6-r3-f2-quiDoIin-2-yl-ethyl)-phenoxvmethvn-ben20icacid !H NMR (300 MHz, CDCb) 5 8.62 (d, IH), 8.44 (d, IH), 8.0 (m, 2H), 7.80 (t, IH), 7.61 (d, IH), 7.21 (d, IH), 7.11 (d, IH), 7.07 (t, IH), 6.94 (bs, IH), 6.76 (bd, IH), 6.68 (d, IH), 5.09 (s, 2H), 3.70 (t, 2H), 3.18 (t, 2H),2.40 (s, 3H). MS (ESI) 398 (M+H)+. Prepared from {2-methyl-6-[3-(2-quinoIin-2-yl-vinyl)-phenoxymethyl]-benzoic acid (example 4a). Example 19 4-Chloromethyl-2-phenyl-oxazole Benzamide(1.21g, lOmmol) is mixed with l,3-dichloroacetone(I.26g, 10 mmol) and the mixture heated to 130 °C and stirred at this temperature for 1 h. The resulting mixture is then cooled, diluted with ethyl acetate, washed with K2CO3 solution (sat.), then brine, dried over MgSOj and concentrated to give the title compound as a solid, which is used without further purification. MS (ESI) 194 (M+H, CI pattern)*. The following compounds are prepared using essentially the same procedure used in Example 19 except using the cited amide in, place of benzamide. Example 19a 2-(5-Methvlthiophen-2-vl)oxazoI -4-ylm ethvl chloride MS (ESI) 214.216 (M+H)"*", CI pattern. Prepared from 5-methylthiophene-2-carboxamide. Example 19b 2-Cyclohexyloxazol-4-vlmethyI chloride MS (ESI) 200,202 (M+H)"\ CI pattern. Prepared from cyclohexanecarboxamide. Example 19c 2-("3-Fluorophenyl)oxazol-4-ylmethyl chloride MS (ESI) 212,214 (M+H)+, CI pattern. Prepared from 3-fluorobenzamide. Example 19d 2-f4-FluorophenyI)oxazol-4-ylmethyl chloride. MS (ESI) 212,214 (M+H)\ CI pattern. Prepared from 4-fluorobenzamide Example 20 4-CUoromethyl-2-phenyl-thiazole A solution of thiobenzamide (I.37g, 10 nunol) and 1,3-dichloro-acetone (1.27g, 10 mmol)in ethanol (25 mL) is warmed to 75 °C and stirred at this temperature for lh. The resulting solution is cooled, poured into ice then brought to pH 8 with K2CO3 solution (sat). This mixture is extracted with ethyl acetate, dried over MgSCU and concentrated to give the title compound. This product is used without further purification. MS (ESI) 210 (M+H)+. Example 21 {2-Methyl-6-r3-(2-pyridin-2-vI-ethoxy)-phenoxvrnethyl1-phenoxy}-acetonitrile To a solution of [2-methyl-6-(3-hydroxy-phenoxymethyl)-phenoxy]-acetonitrile (135 mg, 0.5 mmol, example 25) and 2-(pyridin-2-yl)-ethanol (126 mL, 0.94 mmol) in THF (2 mL) is added triphenylphosphine (262 mg, 1 mmol) folowed by DEAD (118 mL, 0.75 mmol). The resulting solution is stirred for 2h, then concentrated and the residue purified by flash chromatography (silica, 50% ethyl acetate in hexanes) to give the title compound as an oil. MS (ESI) 375 (M+H)+. The following compound is prepared using essentially the same procedure used in Example 21 except using the cited alcohol and phenol in place of 2-(pyridin-2-yI)-ethanol and [2-methyI-6-(3-hydroxy-phenoxymethyI)-phenoxy]-acetonitriIe respectively. 5 Example 21a Methyl 2-methyl-6-{3-F2-(5-methvI-2-phenyloxazol-4-y0ethoxylphenoxymethyi)benzoate MS (ESI) 458 (M+H)+. Prepared from 2-(5-methyl-2-phenyIoxazol-4-yl)ethanol (example 1 la) ) and methyl 2-(3-hydroxyphenoxymethyI)-6-methyIbenzoate (example 5). Example 21b Methyl 2-methyl^rM2H3uinotin-2-vl-eAoxyVpheDOxvmethvn-bea2ogte 'HNMR (300 MHz, CDC13) 8 8.08 (m, 2H), 7.80 (d, 1H), 7.70 (t, 1H), 7.51 (t, 1H), 7.42 (d, 1H), 7.29 (m, 2H), 7.16 (m, 2H), 6.53 (m, 3H), 5.06 (s, 2H), 4.46 (t, 2H), 3.81 (s, 3H), 3.45 (t, 2H), 2.37 (s, 3H). MS (ESI) 428 (M+H)+. Prepared from 2-quinoIin-2-yl-ethanol (example 69a) and 2-(3-hydroxy-phenoxymethyI>6-methyl-benzoate (example 5). Example 22 2-Cyanomethoxy-3-methylbenzaldehyde A mixture of 2-hydroxy-3-methylbenzaldehyde (10.2 g, 75.0 mmoles, Aldrich), bromoacetonitrile (5.70 mL, 82.5 mmoles), and potassium carbonate (11.4 g, 82.5 mmoles) in DMF (150 mL) is heated to 55°C for 3 hours, cooled, then diluted with ether. The mixture is washed with distilled water, saturated NaCI solution, then the organic layer dried over MgS04 and concentrated to give the title compound as a yellow solid. 'HNMR (300 MHz, CDCI3): 5 10.20 (s, 1H), 7.70 (d, 1H), 7.53 (d, 1H), 7.29 (m, 1H), 4.81 (s, 2H), 2.42 (s, 3H). The following compounds are prepared using essentially the same procedure used in example 22 except using the cited phenol in place of 2-hydroxy-3-methy!benzaldehyde. Example 22a 2-Cvanomethoxv-3.5-dichloro-benzaidehvde MS (EI) 229,231 (Mf. Prepared from 3,5-dichlorosaiicylaldehyde. Example 22b 2-Cyanomethoxy-5-chloro-3-methoxy-benzaldehvde MS (EI) 225 (M)+. Prepared from 5-chIoro-2-hydroxy-3-methoxy-benzaldehyde (example 44). Example 22c Methyl 2-(2-formyI-6:methyl-phenoxy)-propionate The title compound is prepared using essentially the same procedure used in example 22 except using methyl 2-bromopropionate in place of bromoacetonitrile. Example 23 (2-Hydroxvmethvl-6-methyl-pheDOxy)-acetonitrile A 2M triglyme solution of sodium borohydride (16.0 mL, 32.1 mmoles) is slowly added to a cooled (-78°C) solution of 2-cyanomethoxy-3-methylbenzaldehyde (II .25g, 642 mmoles, example 22) in THF (180 mL). After stirring for one hour, the reaction is warmed to 0°C for two hours, then quenched with 2N HC1 (16.8 mL) and diluted with ether. The organic layer is isolated and washed with twice with distilled water and brine, then dried over MgS04. The organic solution is concentrated to give the title compound as a yellow oil. The following compounds are prepared using essentially the same procedure used in example 23 except using the cited aldehyde in place of 2-cyanomethoxy-3-methylbenzaldehyde. Example 23 a (2.4-DichlorQ-6-hvdroxvmethvl-phenoxy)-acetonitrile Prepared using 2-cyanomethoxy-3,5-dichloio-benzaidehyde (example 22a) Example 23 b f 4-Ch] oro-2 -hydro xvmeth vl -6-melhox v-phenoxv Vacetonitrii e MS (EI) 227 (M)+. Prepared using 2-cvanomethoxy-5-cruoro-3-methoxy-benzaldehyde (example 22b) Example 23c 2-("2-Hvdroxvmethvl-6-methvI-phenoxv)-propionic acid methyl ester MS (EI) 194 (M)+. Prepared using methyl 2-(2-formyt-6-methyl-phenoxy)-propionate (example 22c). Example 24 (2-Bromomethyl-6-methvl-phenoxv)-acetODitrile Triphenylphosphine (15.2g, 57.8 mmoles) is added to 2-cyanomethoxy-3-me1hylbehzylalcohol (9.3g, 52.5 mmoles, example 23) in THF (175 mL). The mixture is stirred until homogeneous and cooled to 0PC, followed by addition, in three portions, of A^-bromosuccinimide (10.3g, 57.S mmoles). After 90 minutes the reaction is concentrated and the residue purified by column chromatography (silica, 5:1 hex: EtOAe) to yield the title compound as a pale yellow crystalline solid. MS (EI) 239,241 (M)+, Br pattern. The following compounds are prepared using essentially the same procedure used in example 24 except using the cited alcohol in place of 2-cyanomethoxy-3-methyIbenzylalcohol. Example 24a (2-Bromomethyl-4.6-dichloro-phenoxy)-acetonitrile MS (EI) 277 (M-16)\ Prepared from (2,4-dichloro-6-hydroxymethyI-phenoxy)-acetonitrile (example 23a). Example 24b f2-Bromomethyl-4-chloro-6-methoxv-phenoxv)-acetonitrile MS (EI) 289 (My. Prepared from (4-chloro-2-hydroxymethyI-6-methoxy-phenoxy)-acetoiiitrile (example 23b). Example 24 c Metfavl 2-f2-bromomethvl-6-methyl-phenDxy>-propionate MS (EI) 286 (M)+, bromine partem. Prepared from methyl 2-(2-hydroxymethyl-6-methyl- phenoxy)-propionate (example 23c). Example 25 (2-F3 -Hydro xypbenoxvmethvl 1-6-methylpheno xy )acetonitrile Heated (60°C) a mixture of 2-cyanomethoxy-3-methylbenzyl bromide (10.2g, 42.7 mmoles, example 24), resorcinol (18.8g, 171 mmoles), and potassium carbonate (47.2g, 342 mmoles) in acetonitrile (140 mL) for two hours. The reaction is diluted with ether and washed three times with distilled water, once with brine, and dried over MgS04. The organic layer is isolated and concentrated, and the resulting residue is purified by column chromatography (silica, 5% EtOAc/CHsCb) to yield the title compound as a white crystalline solid. MS(EI) 269 (M)+. The following compounds are prepared using essentially the same procedure used in example 25 except using the cited bromide in place of 2-cyanomethoxy-3-methyIbenzyl bromide. Example 25 a F4-Chloro-2-(3-hydroxv-phenoxymethyI)-6-methyl-phenoxv1-acetonitrile Prepared from (2-bromomethyl-4-chloro-6-methyI-phenoxy)-acetonitrile (example 43). Example 25b f 4.6-Di chloro-2-0 -hydroxy -phenoxvmethyiyphenoxvV acetonitrile Prepared from (2-bromomethyI-4,6-dichloro-phenoxy)-acetonitrile (example 24a). Example 26 2-Methvl-6.7-difluoroquinoline To a refiuxing solution of 3,4-difluoroaniline (2.30 mi. 23.2 mmoles), tetrachloro-1,4-benzoquinone (5.70 g, 23.2 mmoles). and concentrated hydrochloric acid (6 ml) in 2-butanol (40 ml) is added crotonaldehyde (1S2 ml, 23.2 mmoles). After 2.5 hours the reaction mixture is concentrated and the resulting residue is stirred in warm (50 °C) THF (15 ml). This mixture is cooled (0 °C) and the solid collected by filtration and washed with cold THF. The solid is stirred in distilled water (200 ml), and the resulting solution made basic with K2CO3 and extracted with EtOAc (3 x 100 ml). The organic extracts are combined and dried over sodium sulfate, and then concentrated to give the title compound. MS (ESI) 180 (M+H)+. The following compounds are prepared using essentially the same procedure used in example 26 sxcept using the cited aniline in place of 3,4-difluoroaniline. Example 26a Z-MethyI-6.8-difluoroquinoline VIS (ESI) 180(M+H)+ Prepared using 2,4-difluoro-aniline. Example 27 ].8-Difluoroquinolin-2-vlmethvI bromide \. solution of 2-methyl-6J8-difIuoroquinoline (0.147 g, 0.820 mmoles, Example 26a), benzoyl wroxide (9.93 mg, 0.0410 mmoles), and A'-bromosuccinamide (0.168 g, 0.943 mmoles) in arbon tetrachloride (20 mL) is heated to reflux for 18 hours. The reaction is concentrated and he resulting residue purified by column chromatography (silica, 3:1 CHjCbihexane, then :H2Cl2) to yield the title compound as a white solid. MS (ESI) 258, 260 (M+H)+, Br pattern. rhe following compounds are prepared using essentially the same procedure used in example 27 :xcept using the cited methyl compound in place of 6,8-difluoro-2-methyl quinoline. Example 27a 6.7-Difluoroqumolin-2-vimethvl chloride 1 .1 _ MS (ESI) 214, 216 (M+H)*. CI pattern. Prepared from 6,7-difluoro-quinoIine (example 26) and NCS in place of NBS. Example 27b 6-FIuoroquinoIin-2-vlmethyI bromide MS (ESI) 240, 242 (M+H)+, Br pattern. Prepared from 6-fluoro-2-methylquinoline. Example 27c 2 -Chloromethyl-6-chJoropyridine MS (ESI) 162,164,166 (M+H)\ Cl2 pattern. Prepared from 6-chloro-2-picoIine and NCS in place of NBS. Example 27d 2-Bromomethvl-benzonitrile MS (EI) 195 (M)+, Br pattern. Prepared from o-tolunitrile. Example 27e Methyl 3-bromomethvl-thiopfaene-2-carboxylate MS (EI) 234 (M)\ Br pattern. Prepared from methyl 3-methyl-thiophene-2-carboxyIate. Example 27f 6,7-DichJoro-2-chIoromethvl-quinoline MS (ESI) 246 (M+H)+. Prepared from 6,7-dichJoro-quinaldine and NCS in place of NBS. Example 27g 5-PhenvIpyridin-2-vlmethvl chloride MS(ESI) 204, 206 (M+H)\ CI partem. Prepared from 5-phenyl-2-methylpyridine (example 104) and NCS in place of NBS. Example 28 3-FfMethvlaminoVmethvn-f2-methoxvethoxv-melhoxv>-ben2ene To a solution of 3-(2-melhoxyethoxy-methoxy)-benzaidehyde (2.10g, 10 mmol, example 8a) in THF (60 mL) is added methylamine (20 mL, 2M in THF) followed by palladium on carbon (210 mg, 10% Pd ). The resulting mixture is stirred for 24 h under an atmosphere of hydrogen gas, then purged with nitrogen, filtered through celite and the filtrate concentrated. The residue is purified by flash chromatography (silica, 10% methanol in dichloromethane) to give the tide compound as an oil. Example 29 1 -Methyl-4-oxo-1 ■4-dihydroouinoUn-2-ylmediyl bromide A solution of l-methyl-4-oxo-l,4-dihydroquinoIin-2-ylmethanol (112 mg, 0.592 mmoles, Coppola, G.M. J. Heterocyclic Chem., 1986,23,1717) and phosphorous tribromide (56.2 uL, 0.592 mmoles) in 3:1 CH2C12:DMF (20 mL) is stirred 18 hours and another portion (20 uL) of phosphorous tribromide is added. After 24 hours distilled water (10 mL) is added and extracted with EtOAc. The organic layer is concentrated and the resulting residue purified by column chromatography (silica, 20:1 CH^ChiMeOH) to yield the title compound as a white solid. MS (ESI) 252, 254 (M+H)+, Br pattern. The following compound is prepared using essentially the same procedure used in example 29 except using the cited alcohol in place of l-methyl-4^xo-l,4HimydToqinnolm-2-ylmetiianoI. Example 29a 4-f en -Butyl cvclohexylmethvl bromide 'H NMR (300 MHz, CDC13): 6 3.27 (d, 2H), 1.93 (m, 2H), 1.81 (m, 2H), 1.54 (m, 2H), 0.98 (m, 4H), 0.84 (s, 9H). Prepared from 4-rerr-butylcyclohexylmethanol (example 30). Example 30 4-/er;-Burylcvclohexvimethanol To a cooled (0°C) solution of 4-/er/-butylcyciohexane-carboxylic acid (3.00g, 16.3 mmoles) in THF (30 mL) is siowiy added a THF solution of borane-THF complex (1.0M, 21.2 mL, 21.2 mmoles). The solution is stirred at room temperature for IS hours, then quenched with 2N HC1 soiution (30 mL), and extracted .with EtOAc. The organic layer is isolated, washed with IN NaOH, dried over sodium sulfate, and concentrated to yield the title compound as a clear oil. 'H NMR (300 MHz, CDClj): 5 2.06 (d, 2H), 1.82 (m, 4H), 1.52 (m, 2H), 0.88 (m, 4H), 0.83 (s, 9H). Example 31 Methyl 4-bromo-3-oxopentanoate To a cooled (0°C) solution of methyl 3-oxopentanoate (9.62 mL, 76.8 mmoles, Acros) in carbon tetrachloride (60 mL) is added dropwise over a period of 45 minutes a solution of bromine (3.96 mL, 76.8 mmoles) in carbon tetrachloride (10 mL). After 30 minutes, let stir at room temperature for one hour. Bubbled N: through reaction mixture for twenty minutes. Concentrated to yield the title compound as a brown oil. MS (EI) 208,210 (M)"", Br pattern. Example 32 Methyl 2-(5-methvl-2-phenyloxazol-4-vI)acetate A solution of benzamide (0.606g, 5.00 mmoles) and methyl 4-bromo-3-oxopentanoate(l.Q5g, 5.00 mmoles, example 31) are heated in toluene (6 ml) to 120°C for 18 hours. The reaction is then purified by column chromatography (silica, 4:1 hex: EtOAc) to give the title compound as a clear oil. MS (APcI) 232 (M+H)+. Example 33 Ethyl 2-methvl-6-f3-(6-phenvlpvridin-2-vlmethoxv)phenoxvmethvnbenzoate A solution of phenylboronic acid (74.0mg, 0.607 mmoles), ethyl 2-[3-{6-chloropyridin-2-ylmethoxy)-phenoxymethyl]-6-methylbenzoate (250mg, 0.607 mmoles, example 6v), and sodium carbonate (77.8mg, 1.21 mmoles) in 1:1 H20:AcCN (8 mL) is stirred under vacuum for five minutes. The reaction is placed under nitrogen, and tetrakis(triphenylphosphine)-palladium(O) (60.7mg) is added followed by heating to 90°C. After two hours, another portion (15mg) of phenylboronic acid is added. After another hour healing is stopped. Distilled water (10 mL) is added, followed by extraction with methylene chloride (twice with 20 mL). The organic extracts are combined and concentrated, and the resulting residue is purified by column chromatography (silica, 6-.1 hex:EtOAc) to yield the title compound. MS (ESI) 454 (M+H)*.' Example 34 1 -Oxyquinolm-2-vlmethvl chloride Partitioned 2-(chloromethyl)quinoline hydrochloride (1.00 g, 4.67 mmoles) between methylene chloride (15 mL) and sodium hydroxide solution (1M, 15 mL) to form the free base. The organic layer is isolated and cooled (0°C), followed by addition of 3-chloroperbenzoic acid (57-86%, 1.13 g, -4.67 mmoles). After stirring at room temperature 18 hours the reaction mixture is washed with dilute sodium hydroxide. The organic layer is isolated and concentrated The resulting residue is purified by column chromatography (silica, 1:1 hex:EtOAc) to yield the title compound as a white solid. MS (EST) 194, 196 (M+H)+, CI pattern. Example 35 {2-[3-(OuinoIin-2-ylmethoxy)phenoxvmethvn-6-methylphenoxy > acetonitrile 3-(QuinoIin-2-yImethoxy)-phenol (1.3g, 5.4 mmol, example 3), (2-bromomethyI-6-methyl-phenoxy)-acetonitrile (1.56 g, 6.5 mmol, example 24), tetrabutylammonium iodide (99 mg, 0.27 mmol) and potassium carbonate (0.45 g, 3.3 mmol) are refiuxed in acetone (20 mL) for 16 h. The reaction is filtered, washed with dichloromethane, concentrated and purified by column chromatograpy (silica, 1 % ether in dichloromethane) to provide the title compound. MS (ESI) 411(M+H)+. The following compounds are prepared using essentially the same procedure used in example 35 except using the cited phenol in place of 3-(quinolin-2-ylmethDxy)-phenoI. Example 35a f2-Methyl-6-r3-fquinoIin-2-vlajninomethvlVphenoxvmethvn-phenoxv}-acetonitrile MS (ESI) 409 (M+Hf. Prepared from 3-(quinolin-2-ylaminomethyl)-phenol (example 10). Example 35b f2-Methvl-6-r3-f2-quinolin-2-yl-vinvI)-phenoxvmethvn-phenoxvl-aceionitri]e MS (ESI) 407 (M+H)+. Prepared from 3-(2-quinolin-2-yi-vinyl)-phenol (example 15). Example 35c (2-Meihvl-6-{3-r2-(pyridin-2-yloxy)-ethoxv1-phenoxymethyl)-phenoxy)-acetonitrile MS (ESI) 391 (M+H)+. Prepared from 3-[2-(pyridin-2-yloxy)-ethoxy}-phenol (example 15a). Example 35d {243-(BenzooxazoI-2-ylaminornethvl Vphenoxymethvn-6-methy 1-phenoxvl -acetonitrile 'H NMR (300 MHz, CDC13) S 7.15 (m, 11H), 5.36 (bs, 1H), 5.08 (s, 2H), 4.67 (s, 4H), 2.37 (s, 3H). MS (ESI) 400 (M+H)+. Prepared from 3-(benzooxazol-2-ylaminomethyI)-phenol (example 10c). Example 35e {2-[3 ^4-Chloro-qmnolin-2-vImemoxymemvlVphenoxymemvl1-6-memvl-phenoxy>-acetonitril e 'H NMR (300 MHz, CDCI3) 6 8.22 (d, 1H), 8.06 (d, 1H), 7.76 (m, 2H), 7.63 (m, 1H), 7.32 (m, 2H), 7.23 (m, 1H), 7.13 (m, 1H), 7.04 (m, 2H), 6.94 (m, 1H), 5.09 (s, 2H), 4.83 (s, 2H), 4.72 (s, 2H), 4.68 (s, 2H), 2.39 (s, 3H). MS (ESI) 459 (M+H)+. Prepared from 3-(4-chloro-quinolin-2-yImethoxymethyI)-phenol (example 74b). Example 35f {2-|"3-(6-Methoxv-quinoliri-2-vlmeihoxymethvl)-phenoxvmethyll-6-methvl-phenoxv)- acetonitrile 'H NMR (300 MHz, CDC!3) 5 8.08 (d, 1H), 7.96 (d, 1H), 7.60 (d, 1H), 7.19 (m, 8H), 6.92 (dd, 1H), 5.07 (s, 2H), 4.84 (s, 2H), 4.71 (s, 2H), 4.66 (s, 2H), 3.93 (s, 3H), 2.39 (s, 3H). MS (ESI) 455 (M+H)\ Prepared from 3-(6-methoxy-quinolin-2-ylmethoxymethyl)-phenol (example 74c). Example 35g {2-Methvl-6-[3-(quinolin-2-vlmethoxvmethvI')-phenoxvinethvI1-DhenoxvKacetonilrile . - Prepared from 3-(quinoIin-2-ylmeihoxymethyI)-phenoI (example 74a). The following compounds are prepared using essentially the same procedure used in example 35 except using the cited bromide in place of (2-bromomethyl-6-methyl-phenoxy)-acetomtrile. Example 36a 2-{2-Methyl-6-r3^qumolin-2-ylmethoxvVphenoxvrnethvn-phenoxv}-Dropionicacidmedivl ester MS (ESI) 457 (M+H)+. Prepared using methyl 2-(2-bromomethyl-6-methyI-phenoxy>- propionate (example 24c). Example 36b f 2.4-Dichloro-6- r3-fquinolin-2-vlmetriQxy Vphenoxymethyll-phenoxy) -acetohitrile MS (ESI) 465 (M+H)+,C12 pattern. Prepared from (2-bromomethyl-4,6-dichloro-phenoxy)- acetonitrile (example 24a) Example 36c {4^morc-2-memvl^f3-fQumolin-2-vlmemoxvVphenoxymemvn-phenoxy}acetonitrile MS (ESI) 445 (M+H)+. Prepared from (2-bromomethyl-4-chloro-6-methy!-phenoxy)-acetonitrile (example 43). Example 36d f2-tert-Butvl-6-r3-fquinolin-2-vImethoxv)-phenoxvmethvn-pfaenoxv>-acetonitrile MS (ESI) 453 (M+H)+. Prepared from (2-bromomethyl-6-ten-butyl-phenoxy>acetonitriIe (example 43 a). Example 36e f4-Chioro-2-methoxy-6-f3-fquinolin-2-viniethoxvVphenoxvmethvIl-phenoxv}-acetonitrile MS (ESI) 463 (M+H)+, CI pattern. Prepared from (2-bromomethyI-4-chloro-6-methoxy-phenoxy)-acetonitrile (example_24b). Example 36f 2-r3-fQuinQlin-2-vlmelhoxy)-phenoxvmethvn-ben2onitrile MS (ESI) 386 (M+H)+. Prepared from 2-bromomethyl-benzonitrile (example 27d). Example 36g Methyl 2-f34QuinoIiii-2-ylmethoxv)-phenoxvmethyn-thiopfaene-2-carpoxvlate MS (ESI) 406 (M+H)+. Prepared from methyl 3-bromomethyl-thiophene-2-carboxylate (example 27e). Example 36h Ethyl f2-memyl-6^r3-fquiDoliD-2-ylmethoxv)-pheDoxymethyIl-pfaenoxy}-acetate MS (ESI) 457 (M+H)+. Prepared from ethyl (2-brDmomethyI-6-methyl-phenoxy)-acetate (example 43b). Example 36i Ethyl 7-r3-(quinoIin-2'yIrnethoxy)-phenoxvmethvll-berizofuran-2-carboxviate MS (ESI) 354 (M+H)+. Prepared from ethyl 7-bromomethyl-ben2ofuran-2-carboxylate (example 94). Example 36j Ethyl {2-methvl-6-F3-rnethvl-5-(-quinolin-2-vlmethoxyVphenoxvmethvn-phenoxv>-acetate The title compound is prepared using essentially the same procedure used in example 35 except using 3-meihyl-5-(qmnoUn-2-y\Tnethoxy)-phenol (example 55) in place of / 3 The following compounds are prepared using essentially the same procedure used in example 35 except using the cited phenol in place of 3-(quinolin-2-yImethoxy)-phenol and (2-bromomethyI-4-chloro-6-methyl-phenoxy)-acetonitrile (example 43) in place of (2-bromomethyl-6-methyl- phenoxy)-acetonitril e. Example 36k (4-Chloro-2-memvl-6^r3-f2-PYridin-2-vl-ethoxv)-phenoxymethvIl-phenoxv)-acetonitrile 'HNMR (300 MHz, CDC13) 5 8.56 (d, IH), 7.62 (m, IH), 7.30 (m, IH), 7.18 (m, 3H), 6.57 (m, 4H), 4.99 (s, 2H), 4.67 (s, 2H), 4.36 (t, 2H), 327 (t, 2H), 2.36 (s, 3H). MS (ESI) 409 (M+H)+. Prepared from 3-(2-pyridin-2-yI-ethaxy)-phenoI (example 71a). Example 361 {2-r3-(BenzooxazoI-2-ylaminomethyl)-phenoxymetbvIl-4-chloro-6-methyl-phenoxv>- acetonitrile 'HNMR (300 MHz, CDC13) 6 7.14 (m, 10H), 5.35 (bs, IH), 5.04 (s, 2H), 4.67 (d, 2H),4.63 (s, 2H), 2.34 (s, 3H). MS (ESI) 434 (M+H)+. Prepared from 3-(benzooxazoI-2-ylaminomethyI)- phenol (example 10c). Example 37 2-r3-f2-Chloromethvl-benzvloxy)-phenoxvmethyll-quinoiine The title compound is prepared using essentially the same procedure used in example 35 except using excess 1,2-bis-chloromethyl-benzene in place of (2-bromomethyI-6-methyl-phenoxy)- acetonitriie and without using tetrabutylammonium iodide. MS (ESI) 390 (M+H)+, CI pattern. Example 38 i2-r3-fOuinolin-2-vlmethoxv)-phenoxvmethvn-phenvll-acetonitriie Sodium cyanide (14 mg, 0.28 mmol) is added to a solution of 2-[3-(2-chloromethyl-benzyloxy)-phenoxymethylj-quinoline (110 mg, 0.28 mmol, example 37) in DMSO (5 mL) and the reaction is stirred 5 h. The reaction is partitioned between water and ethyl acetate, the organic phase is washed with water, dried and concentrated to provide the title compound which is used without further purification. MS (ESI) 3S1 (M+H)+. Example 39 f2-[3-fQuinoxaIin-2-vlmethoxv)phenoxymethyll-6-methvlphenoxv}acetonitrile A solution of (2-[3-hydroxyphenoxymethyl]-6-methylphenoxy)acetonitrile (100 mg, 0.37 mmol, example 25), quinoxalin-2-ylmethyl chloride [72 mg, 0.40 mmol (See Chem. Ber. 1987,120, 649-651)] in DMF (1 mL) is heated with potassium carbonate (105 mg, 0.75 mmol) at 60 °C for 16 h. The reaction is filtered and pardoned between ethyl acetate and water. The organic phase is washed with water, dried over magnesium sulfate, concentrated and purified by column chromatography (silica, 30% ethyl acetate in hexanes) to provide the title compound, MS (ESI) 412 (M+H)+. The following compounds are prepared using essentially the same procedure used in example 39 except using the cited halide in place of quinoxalin-2-ylmethyl chloride. Example 39a f2-r3-(7-ChlorcKiso Example 39b {2-Methvl-6-[3-fnaphthalen-2-vImethoxvVphenoxvmethvn-phenoxy)-acetonitriJe MS (ESI) 410 (M+H'f. Prepared from napthalen-2-ylmethyl chloride. ExampJe 39c (2-r3-(4-tert-Butvl-benzvloxy>-phenoxymethvll-6-methvl-phenoxy}-aceionitriIe MS (ESI) 416 (M+H)*. Prepared from 4-/ert-butylbenzyI chloride. Example 39d f2-Methvl-6-r3-(2-phenoxv-ethoxv)-phenoxvm ethyl Vphenoxy)-acetonitrile MS (ESI) 390 (M+H)\ Prepared from 2-phenoxy-ethyl-bromide. Example 39e {2-Methvl-6-r3-(3-phenvl-propoxv)-phenoxvroelhvl1-phenoxvKacetoDitriie MS (ESI) 3S8 (M+H)+. Prepared from 3-phenyI-propyI bromide. Example 39f {2-MethvI-6-f3^3-phenoxv-penzvloxy)-phenoxvmethyll-phenoxv>-acetonrtrile MS (ESI) 452 (M+H)+. Prepared from 3-phenoxy-benzyI chloride. Example 39g {2-r3-(3-Methoxy-benzvloxy)-phenoxvmelhvl]-6-methvI-phenoxvKacetonitriIe MS (ESI) 390 (M+H)+. Prepared from 3-methoxy-benzyi chloride. Example 39h {2-("3-(3.4-Dichloro-benzvtoxvVphertoxvmethvlV6-methvl-phenoxv}-acetomtrile MS (ESI) 428 (M+Hf. Prepared from 3,4-dichloro-benzyi chloride. Example 39i {2-r3-('6.7-DifluoroquinoIiii-2-vlmeihoxv)phenoxvinethv11-6-methv]-phenQxv}acetoniirile MS (ESI) 446 (M+H)+. Prepared from 6,7-difluoroquinolin-2-ylmethyl chloride (example 27). Example 39] {2'f3-(6.8-DifluQroquinolin-2'ylmethoxy)pbenoxvmethvn-6-niethylphenoxv}acetonimle MS (ESI) 446 (M+H)+. Prepared from 6,8-difluoroquinolin-2-ylmethyl bromide (example 27a). Example 39k (2-Methvl-6-r3^1-oxyquinolin-2-vlmethoxy)pheDOxvmethynphenoxv}acetonitrile MS (ESI) 427 (M+H)+. Prepared from l-oxyquinoiin-2-ylmethyl chloride (example 34). Example 391 {2-f"3 -(6-FluoroquinoIin-2-vimethoxv)phenoxvmethyl1-6-melhvlphenoxy } acetonitriJe MS (ESI) 429 (M+Hf. Prepared from 6-fluoroqumoIin-2-ylmethyl bromide (example 27b). Example 39m (2-Methyl-6-f3-fl-methvl-4-oxo-1.4-dihvdroquinolin-2-vlmethDxy')phenoxvmethvn-phenoxy} acetonitrile MS (ESI) 441 (M+H)+. Prepared from l-methyI-4-oxo-l,4-dihydroquinolin-2-ylmethyl bromide (example 29). Example 39n {243-f4-Chloroquinolm'2-vlmethoxv)phenoxymethyI1-6-memvbhenoxv>acetomtrile MS (ESI) 445 (M+H)+. Prepared from 4-chIoroquinolin-2-ylmethyl chloride (example 46). Example 39o ?2-f3-('7-Chloroquinolm-2-vlmethoxv)phenoxymethvil-6-methvlphenoxv} acetonitrile MS (ESI) 445 (M+H)\ Prepared from 7-chloroqumolin-2-ylmethy! chloride (example 46a). Exampie 39p {2-r3-f6-Methoxvquinolin-2-vlmeihoxv)phenoxvmethvn-6-methvlphenoxv)acetonitrile MS (ESI) 441 (M+H)+. Prepared from 6-methoxyquinolin-2-ylmethyl chloride (example 46b). Example 39q (2-Methvl-6-r3-(pyridin-4-ylmethoxy)-phenoxvmethvn-phenoxv}-acetonitrile 'H NMR (300 MHz, CDC13) 5 8.62 (bd, 2H), 7.24 (m, 6H), 6.62 (m, 3H), 5.08 (s, 2H), 5.06 (s, 2H), 4.70 (s, 2H), 2.39 (s, 3H). MS (ESI) 361 (M+Hf. Prepared from 4-chloromethyl-pyridine hydrochloride. Example 39r (2-MethvI-6- r3-(pyridin-2-vImethoxv)-phenoxymethvn-phenoxv) -acetonitrile 'H NMR (300 MHz, CDC13) 5 8.60 (d, 1H), 7.72 (m, 1H), 7.52 (d, 1H), 7.21 (m, 5H), 6.63 (m, 3H), 5-20 (s, 2H), 5.04 (s, 2H), 4.69 (s, 2H), 2.39 (s, 3H). MS (ESI) 361 (M+H)+. Prepared rron 2-chIoromethyl-pyridine hydrochloride. Example 39s j 2-Methy l-6-n-(pyridin-3-ylmethoxv)-phenoxymethyn-phenoxv} -acetonitrile >H NMR (300 MHz, CDC13) 5 8.68 (bs, 1H), 8.59 (bd, 1H), 7.78 (m, 1H), 7.24 (m, 5H), 6.63 (m 3H), 5.07 (s, 2H), 5.06 (s, 2H), 4.70 (s, 2H), 2.39 (s, 3H). MS (ESI) 361 (M+H)+. Prepared frorr 3-chloromethyI-pyridine hydrochloride. Example 39t {2-[3^6.7-Dichbro-quino[in-2-vlmethoxv)-phenoxvmethvl1-6-rnethvl-phenoxvl-acetonitriie 'H NMR (300 MHz, CDC!3) 5 8.20 (s, 1H), 8.10 (d. 1H), 7.94 (s. 1H)? 7.70 (d, 1H), 7-20 (m, 4H). 6.65 (m. 3H). 5.34 (s, 2H), 5.05 (s, 2H), 4.69 (s,2H).2.38 (s, 3HV MS (ESI) 479 (M+H) Prepared from 6.7-dichloro-2-chloromethy]-quinoline (example 27f). Example 39u {2-Methvl-6-[3-(2-phenvt-thia2ol-4-vlme^iQxvVphenoxvmethvn-phenoxvl-acetonitrHe MS (ESI) 443 (M+H)\ Prepared from 4-chbromethyl-2-phenyI-thiazole (example 20). The following compounds are prepared using essentially the same procedure used in example 39 except using the cited phenol in place of (2-[3-hydroxyphenoxymethyl]-6-methylphenoxy)acetonitrile and 6-fluoroquinolin-2-ylmethyl bromide (example 27b) in place of quinoxalin-2-ylmethyl chloride. Example 40a f4-Chloro-2-r3-(6-fluoroquinolin-2-ylmethoxy)phenoxymethvI]-6-methylphenoxvlacetonitrile MS (ESI) 463, 465 (M+H)+, CI pattern. Prepared from (2-[3-hydroxyphenoxymethyl]-4-chloro-6-methylphenoxy)acetonitrile (example 25a). Example 40b {2,4-Dichloro-6-r3-(6-fluoroquinolin-2-ylmethoxv)phenoxymethvnphenoxv)acetonitrile MS (ESI) 483, 485,487 (M+H)\ Cl2 pattern. Prepared from [4,6-dichloro-2-(3-hydroxy-phenoxymethyl)-phenoxy]-acetanitrile (example 25b) Example 41 {2-Methvl-6-r3-(quinoIin-2-vlaminomethyl)-phenoxvmethvn-phenoxy)-acetic acid To a solution of {2-methyl-6-[3-(quinolin-2-ylaminomethyl)-phenoxymethyI]-phenoxy}-acetonitrile (134 mg, 0.31 mmol, example 35a) in methanol (1 mL) is added THF (1 mL) followed by sodium hydroxide solution (0.2 mL, 10 N). The resulting mixture is warmed to 60 °C and stirred at this temperature for 3h. The reaction mixture is then cooled to room temperature and acidified to ca. pH 5 with hydrochloric acid (1 mL, 2N), then extracted with ethyl acetate, washed with brine, dried over MgS04 and concentrated. The residue is purified by flash chromatography (silica, 10% methanol in dichloromethane) to give the title compound. H NMR (300 MHz. CDCb) 8 8.10 (d. 1H), 7.80 (d, 1H). 7.68 (t, 2H), 7.40 (t7 1H), 7.25 (m, 2H), 7.04 (m, 3H), 6.90 (m, 3H), 6.6 (bs, IH), 5.15 (s, 2H), 4.60 (d, 2H), 4.50 (s, 2H), 2.27 (s, 3H). MS (ESI) 429 (M+Hf. The following compounds are prepared using essentially the same procedure used in example 41 except using the cited nitrile or ester in place of {2-raethyl-6-[3-(quinolm-2-yIaminomethyl>-phenoxymethyl]-phenoxy}-acetonitrile. Example 41a f2-Methyl-6-f3-("2-quinolin>2-vl-vinyl>-phenoxvmethvll-phenoxv}-aceticacid !H NMR (300 MHz, DMSO) d 8.38 (d, IH), 8.01 (d, IH), 7.97 (d, IH), 7.89 (d, IH), 7.83 (d, IH), 7.78 (dt, IH), 7.59 (dt, IH), 7.53 (d, IH), 7.44 (bd, IH), 7.36 (ro, 3H),725 (bd, IH), 7.11 (t, IH), 7.02 (dt, IH), 5.25 (s, 2H), 4.54 (s, 2H), 2.32 (s, 3H). MS (ESI) 426 (M+H)+. Prepared from {2-methyl-6-[3-(2-qumoIin-2-yl-vinyl)-pheDOxymethyl]-phenoxy}-acetonitrile (example 35b). Example 41b f2-MethyI-6-f3-r2-(pyridin-2-vloxy)-ethoxvl-phenoxymethvU-phenoxy)-acetic acid 'H NMR (300 MHz, DMSO) d 8.17 (dd, IH), 7.72 (m, IH), 7.29 (dd, IH), 7.20 (m, 2H), 7.07 (t, IH), 6.99 (m, IH), 6.85 (d, IH), 6.60 (m, 3H), 5.13 (s, 2H), 4.57 (t, 2H), 4.49 (s, 2H), 4.30 (t, 2H), 2.28 (s, 3H). MS (ESI) 410 (M+H)+. Prepared from (2-methyl-6-{3-[2-(pyridin-2-yIoxy)-ethoxy]-phenoxymethyl}-phenoxy)-acetonitrile (example 35c). Example 41c f2-r3-(7-Chloro-isoquinolin-3-vlmethoxy)-phenoxvmethyl1-6-methvl-pherioxv}-acetic acid 'H NMR(300 MHz, CDC13) 5 9.13 (d, IH), 7.96 (s, IH), 7.79 (s, IH), 7.74 (d, IH), 7.65 (d, IH), 7.30 (d, IH), 7.20 (d, IH), 7.10 (m,2H), 6.81 (s, IH), 6.62 (d, IH), 6.49 (d, IH), 5.25 (s, 2H), 5.16 (s, 2H), 4.59 (s, 2H), 2.37 (s, 3H). MS (ESI) 464 (M+H, CI pattern)*. Prepared from {2-[3-(7-cWoro-isoquinolin'3-ylmethoxy)-phenoxymethyl]-6-methyl-phenoxy}-acelonitrile (example 39a). Example 4 Id {2-Methvl-6-r3-fnaphthalen-2-vlmethoxvVphenoxvmethvn-phenoxv}-aceticacid 'H NMR (300 MHz, CDCh) 8 8.00 (m, 3H), 7.48 (dd, ] H)5 7.43 (m, 2H), 7.23 (m, 2H), 7.36 (m, 2H), 7.05 (t, 1H), 6.62 (m, 1H), 6.55 (m, 2H). MS (ESI) 429 (M+H)+. Prepared from {2-methyl-6-[3-(naphthaien-2-yImethoxy)-phenoxymethyI]-phenoxy}-acetonitrile (example 39b). Example 41 e f2-r3-f4-ten-Butvl-ben2vloxy)-phenoxvmethyn-6-methvl-phenoxy|-aceticacid !H NMR (300 MHz, CDC13) 5 7.38 (m, 3H), 7.27 (m, 2H), 7.24 (d, 1H), 7.17 (d, 1H), 7.10 (d, 1H), 6.59 (m, 3H), 5.07 (s, 2H), 4.98 (s, 2H), 4.57 (s, 2H), 2.33 (s, 3H), 1.33 (s, 9H). MS (ESI) 435 (M+H)+. Prepared from {2-[3-(4-/er/-butyl-benzyloxy)-phenoxymethyl]-6-mefliyl-phenoxyj-acetonitrile (example 39c). Example A\ f (2-Methvl-6-f3-(2-phenoxv-ethoxvVphenoxvmethvn-phenoxy>-aceticacid 'HNMR(300 MHz, CDC13) o 7.03-7.33 (m, 6H), 6.95 (m, 3H), 6.57 (m, 3H), 5.07 (s,2H), 4.55 (s, 2H),4.29 (m, 4H), 2.33 (s, 3H). MS (ESI) 409 (M+H)+. Prepared from {2-methyl-6-[3-(2-phenoxy-ethoxy)-phenoxymethyl}-phenoxy)-acetonitrile (example 39d). Example 41g f2-Metbvl-6-r3-f3-phenyl-propQXvVphenoxymelhvI1-phenoxy}-aceticacid _ 'H NMR (300 MHz, CDC13) 5 7.07-7.41 (m, 9H), 6.54 (m, 3H), 5.08 (s, 2H), 4.58 (s, 2H), 3.94 (t, 2H), 2.80 (t, 2H), 2.34 (s, 3H), 2.09 (qn, 2H). MS (ESI) 40-7 (M+H)+. Prepared from {2-methyl-6-[3-(3-phenyl-propoxy>phenoxymethyI]-phenoxy}-acetonitrile (example 39e). Example 4 Ih {2-Methvl-6-r3-f3-phenoxv-benzvloxv)-phenoxvmethviVphenoxy_)-aceticacid !H NMR (300 MHz, CDC13) 5 7.31 (m. 4H). 7.06-7.25 (m, 6H), 7.0! (m, 2H). 6.94 (m, IH). 6.57 (m, 3H). 5.06 {s, 2H), 4.99 (s, 2H). 4.56 (s. 2H), 2.33 (s, 3H). MS (ESI) 471 (M+Hf. Prepared from E2-methyI-6-[3-(3-phenoxy-benzylox'y)-phenoxymethyI]-phenoxy}-acetonitrile (example 39f>- Example 411 {2-r3-(3-Methoxv-benzyloxy)-phenoxvmethvl'[-6-methyl-phenoxy}-acetic acid MS (ESI) 409 (M+H)+. Prepared from {2-[3-(3-methoxy-benzyloxy)-phenoxymethyIj-6-methyl- phenoxyj-acetonitrile (example 39g). Example 4I j f2-r3-f3.4-Diehloro-benzyloxv)-phenoxvmethvIl-6-methyl-phenoxY}-acetic acid (H NMR (300 MHz, CDC13) 5 7.60 (d, IH), 7.51 (d, IH), 7.30-7.38 (m, 2H), 7.28 (d, IH), 7.23 (d, IH), 7.17 (d, IH), 6.66 (m, 3H), 5.16 (s, 2H), 5.05 (s, 2H), 4.65 (s, 2H), 2.42 (s, 3H). MS (ESI) 447 (M+H)+. Prepared from {2-[3-(3,4-dicWoro-benzyloxy>phenoxymethyi]-6-methyl-phenoxy}-acetonitrile (example 39h. Example 41k {2-f3-(6.7-Difluoroquinolin-2-vlmethoxv)phenoxvmethvll-6-methvlphenQxy)acetic acid m.p. 94-95 °C. 'H NMR (300 MHz, CDCI3): 6 8.10 (d, IH), 7.73 (m, IH), 7.56 (d, IH), 7.44 (d, IH), 7.29 (s, IH), 7.18 (m, IH), 7.08 (m, 2H), 6.79 (s, IH), 6.61 (d, IH), 6.51 (m, IH), 5.31 (s, 2H), 5.15 (s, 2H), 4.61 (s, 2H), 2.35 (s, 3H). MS (ESI) 466 (M+H)+. Prepared from {2-[3-(6,7-dif]uoroquinoIm-2-ylmethoxy)phenoxymethyI]'6-methyl-phenoxy}acetonitrile (example 39i). Example 411 f2-r3-(6.8-Difluoroqumolin-2-vlmethoxy)phenoxvmethvll-6-methvlphenoxv)aceiicacid m.p. 137-141 PC. 'HNMR(300MHz,CDCb): 8 8.16 (d. IH), 7.79 (d. IH), 7.29-7.05 (m, 6H), 6.71 (5, IH), 6.61 (m,2H), 5.53 (s, 2H). 5.10 (s, 2H), 4.57 (s,2H). 2.33 (s. 3H). MS (ESI) 466 (M+H)\ Prepared from {2-[3-(6,8-dif]uoroqmnolin-2-ylmethoxy)phenoxymethyl}-6-methyiphenoxy}aceionirriIe (example 39j). Example 41m {2-Methv]-6-r3-fl-oxvquinolin-2-vlmethoxy)phenoxvmeihvnphenoxy}aceticacid m.p. 146-147 °C 'H NMR(300 MHZ, CDC13): 5 8.73 (d, 1H), 8.01 (m, IH), 7.93 (m, 1H), 7.89 (m, 1H), 7.70 (m, IH), 7.55 (d, 1H), 7.26 (m, 2H), 7.01 (m, 2H), 6.75 (m, 3H), 5.69 (s, 2H), 5.26 (s, 2H), 4.47 (s, 2H), 2.24 (s, 3H). MS (ESI) 446 (M+H)+. Prepared from {2-methyl-6-[3-(l-oxyquinolm-2-yImemoxy)phenoxymethyI]phenoxy}-acetomtrile (example 39k). Example 41n {2-f3-(6-Fluoroquinolin-2-vlmetfaQxy)ofaenoxvmgthvn-6-methvlphenoxv> acetic acid m.p. 160-161 °C. ,HNMR(300MHz,CDCl3): 6 8.17 (m, 2H), 7.72 (d, 1H), 7.48 (m, 2H), 7.27 (m, IH), 7.19 (d, 1H), 7.08 (m, 2H), 6.63 (s, IH), 6.62 (d, IH), 6.53 (d, IH), 5.35 (s, 2H), 5.14 (s, 2H), 4.61 (s, 2H), 2.34 (s, 3H). MS (ESI) 44? Example 41 o (2-Methyl-6-r3-(l-methyU-oxo-1.4-dihvdroquinoIin-2-vLmethoxv'lphenoxymethvn-phenoxylacetic acid m.p. 192-194°C. 1HNMR(300MHz, 1:1 CDCly. CDaOD): 6 8.29 (m, IH), 7.76(m, 2H), 7.41 (m, IH), 7.25-6.92 (m, 4H), 6.81-6.41 (m, 4H), 5.11 (m, 4H), 4.39 (s, 2H), 3.88 (s, 3H), 2.27 (s, 3H). MS (ESI) 460 (M+H)+. Prepared from {2-methyl-6-[3-(I-methyl-4-oxo-l,4-dihydroquinolin-2-ylmethoxy)phenoxymethyI]phenoxy}aceionitrile (example 39m). Example 41 p (4-Chioro-2-r3-f6-fluoroQuinolin-2-vlmethoxvlDhenoxvmethvn-6-methvlphenoxv)aceiicacid m.p. 140-14PC. 'H NMR (3O0 MHz. 5:1 CDC13: CDjOD): 8 8.20 (d, IH), 8.07 (m, IH), 7.69 (d. IH), 7.50 (m. 2H), 7.25 (s, IH), 7.16 (m, IH), 7.11 (s, IH). 6.67 (s, 2H), 5.07 (s, 2H), 4.24 (s, 2H), 2.25 (s. 3H). MS (ESI) 482, 484 (M+H)\ CI pattern. Prepared from {4-chioro-2-[3-(6-fluoroquinolin-2-ylmethoxy)phenoxymethyIJ-6-methylphenoxyjacetonitrile (example 40a). Example 41q t2.4-Dichloro-6-[3-(6--fluoroquinolin-2-vimetfaoxv)phenoxymethyI1phenoxv^acetic acid m.p. 189-190°C. 'H NMR (300 MHz, 5:1 CDCI3: CD3OD): 5 8.22 (d, IH), 8.07 (m, IH), 7.73 (d, 1H), 7.52 (m, 2H), 7.35 (m, 2H), 7.21 (m, IH), 6.72 (s, IH), 6.65 (m, 2H), 5.34 (s, 2H), 5.22 (s, 2H), 4.68 (s, 2H). MS (ESI) 502, 504, 506 (M+H)+, Cl2 partem. Prepared from {2,4-dicUoro-6-[3-(6-fluoroqumoIin-2-ylmethoxy)phenoxymethyl]phenoxy}acetonitrile (example 40b). Example 41r (2-Methvl-6-f3-(2-pvridm-2-vl-ethoxy)-phenQxvinethvIl-pheDoxv) -acetic acid 1HNMR(300MHz,DMSO)d 8.50 (d IH), 7.73 (dt, IH), 7.36 (d, IH), 7.20 (m,4H), 7.04 (m, " IH), 6.58 (m,2H), 6.50 (d, IH), 5.77 (s, 2H), 5.15 (s, 2H). 4.35 (m, 4H), 3.20 (t, 2H), 2.25 (s, 3H). MS (ESI) 394 (M+H)+. Prepared from {2-methyl-6-[3-(2-pyridin-2-yl-ethoxy)-phenoxymethyI3-phenoxy}-acetonitrile (example 21). Example 41s {2-r3-fOuinolm-2-ylmethoxv)phenoxvmethyll-6-rDethylDhenoxv>-acetic acid m.p. 154-157 °C; 'HNMR(300 MHz, CDC13)8 8.25 (d, IH), 8.19 (d, 1H),7.81 (d, 1H),7.77-7.70 (m, 2H), 7.60-7.55 (m, IH), 7.27 (dd, IH), 7.18 (d, IH), 7.13-7.04 (m, 2H), 6.85 (t, IH), 6.61 (dd, IH), 6.53 (dd, IH), 5.40 (s, 2H), 5.18 (s, 2H), 4.62 (s, 2H),2.35 (s, 3H); MS (ESI)43( (M+H)+. Prepared from {2-[3-(quinolin-2-ylmethoxy)phenoxymethyI]-6-methylphenoxy}acetonitrile (example 35). Example 4 It {2-Methv!-6-!"3-(quinoxalin-2-vlmethoxv)-Dhenoxvmethvll-phenoxv}-acetic acid 'H NMR (300 MHz, DMSO-d6) 6 9.07 (s, 1H), 8.14-8.05 (m, 2H). 7.87-7.82 (m, 2H), 7.19-7.05 (m. 3H), 6.97-6.92 (m, 1H), 6.77 (s, 1H), 6.67-6.57 (m, 2H), 5.41 (s, 2H), 5.19 (s, 2H), 4.10 (s, 2H), 2.21 (s, 3H); MS (ESI) 431 (M+Hf. Prepared from {2-[3-(qumoxaIiri-2-ylmethoxy)-phenoxymethyl]-6-methylphenexy}acetonitrile (example 39). Example 41 u 2-f2-Methvl-6-f3-(quinoIin-2-ylmelhQXyVphenoxymethyn-phenoxy}-propiQnic acid 'H NMR (300 MHz, DMSO-d*) d 8.40 (d, 1H), 7.99 (dd, 2H), 7.77 (dd, 1H), 7.67-7.58 (m, 2H), 7.22-7.10 (m, 3H), 6.98 (dd, 1H), 6.73 (s, 1H), 6.60 (dd, 2H), 5.33 (s, 2H), 5.19 (dd, 2H), 4.40-4.34 (m, 1H), 2.24 (s, 3H), 1.35 (d, 3H); MS (ESI) 444 (M+H)*. Prepared fom methyl 2-{2-methyl-6-[3-(quinoIin-2-ylmethoxy)-phenoxymethyl]-pfaenoxy}-propionate (example 36a). Example 41 v {2.4-DichloTo-6-[3-fquinoUn-2-vlniethoxvVphenoxvtnethyn-phenoxv>-aceticacid m.p. 201-203 °C; 'H NMR (300 MHz, DMSO-de) d 8.38 (d, 1H), 7.98 (dd, 2H), 7.76 (dd, 1H), 7.66-7.57 (m, 2H), 7.54 (d, 1H), 7.39 (d, 1H), 7.18 (dd, 1H), 6.75 (s, 1H), 6.66-6.61 (m, 2H), 5.33 (s, 2H), 5.28 (s, 2H), 4.48 (s, 2H); MS (ESI) 484,486 (M+H; Cl2)+. Prepared from {2,4-dichloro-6-[3-(quinoIin-2-ylmethoxy)-phenoxymethyI]-phenox>,}-acetonitrile (example 36b). Example 4 lw {4-Chloro-2-methyl-6-r3-(quinoIin-2-ylmethoxy)-phenoxvrnethvll-phenoxy}aceticacid lH NMR (300 MHz, CDC13) 5 8.37 (d, 1H), 8.02 (d, 1H), 7.93 (d, 1H), 7.78-7.70 (m, 2H), 7.60 (t, 1H), 7.24-7.15 (m, 3H), 6.73 (s, 1H), 6.66-6.61 (m, 2H), 5.34 (s, 2H), 5.14 (s, 2H), 4.27 (s, 2H). 2.29 (s, 3H); MS (ESI) 464 (M+H)+. Prepared from {4-chloro-2-methyl-6-[3-(qumolin-2-ylmethoxy)-phenoxymethy!]-phenoxy}acetonitrile (example 36c). Example 41x (2-tert-Butvl-6-r3-fqmnolm-2-vtmethoxvVphenoxvmethvn-phenoxv)-acericacid 'HNMR(300MH2.CD3OD)dS.33 (d, IH), 8.01 (d, IH), 7.90(d. IH), 7.80-7.55 (m. 3H), 7.35 -7.28 (m. 2H). 7.15-7.01 (m, 2H), 6.71 (s, IH), 6.60 (d, 2H), 5.40 (s, 2H), 5.10 (s, 2H), 4.40 (s, 2H), 1.41 (s, 9H); MS (ESI) 472 (M-^H)". Prepared from {2-tert-buryl-6-13-{qmnolm-2-ylniethoxy)-phenoxyineihyI]-phenoxy}-acetonitriJe (example 36d). Example 41 y f4-Cfaloro-2-methoxv-6-r3-(QuinQlin-2-vlmeihoxv)-phenoxvmeIhvn-phenoxv}-aceiic acid M.P. 185-190 °C, 'H NMR (300 MHz, DMSO) d 8.45 (d, IH), S.04 (t, 2H), 7.82 (t, IH), 7.71-7.76 (m, 2H), 7.23 (i, IH), 7.13 (d. IH), 7.02 (d, IH), 6.77 (d, IH), 6.71-6.67 (m, 2H), 5.38 (s, 2H), 5.28 (s, 2H), 4.62 (s, 2H), 3.86 (s, 3H); MS (ESI) 480 (M+H)*. Prepared fiom {4-chloro-2-methoxy-6-[3-(qumoIin-2-ylmethoxy)-phenoxymethyI]-phenoxy}-acetonitrile (example 36e). Example 41z 2-r3-(QumoHn-2-vlmelhoxv)-phenoxymetfavn-benzoic acid 'HNMR (300 MHz, CDCb) 6 8.13 (d, IH), 8.03 (d, IH), 7.79 (d, IH), 7,70-7.41 (m, 5H), 7.10 (t, IH), 6.67 (s, 1H),5.58 (d, 2H), 5.51 (s, 2H), 5.36 (s, 2H); MS (ESI) 386 (M+H)\ Prepared from 2-[3-(quinoIin-2-ylmeihoxy)-phenoxymethyl]-benzonitr:le (example 36f)- Example41aa 2-r3-fOuinolin-2-vlmethoxv)-pheDOxymethvn-thiophene-2-carboxylicacid 'H NMR (300 MHz, CDjOD) d 8.36 (d, IH), 8.04 (d, IH), 7.94 (d, IH), 7.78 (t, IH), 7.70 (d, IH), 7.61 (t, IH), 7.48 (d, IH). 7.13-7.19 (m, 2H), 6.70 (s, IH), 6.61 (dt, 2H), 5.46 (s, 2H), 5.32 (s, 2H); MS (ESI) 392 (M+H)*. Prepared from methyl 2-[3-(quinolin-2-ylmcthoxy)-phenoxymethyl]-thiophene-2-carbaxylate (example 36g)- Example 4 lab |2-r3-fOuinoiin-2-vimethoxv>-phenox\-melhviVphenvU-acelic acid 'H NMR (300 MHz. CDCb) 6 8.20-8.11 (m, 2H). 7.85-7.52 (m. 4H), 7.40-7.27 (m, 4H), 7.18-7.!0 (m. IH), 6.67-6.46 (m, 3H), 5.35 (s, 2H). 5.12 (s, 2H}, 3.76 (s, 2H); MS 400 (M+H)*. Prepared from {2-[3-(quino]in-2-ylmethoxy}-pbenoxymethyl]-pheny]}-acetonitriIe (example 38). Example 4lac {4-Chlorc'-2-methvl-6-r3-("quinolin-2-vlmelhoxv>-benzvloxvmethvI1-Dhenoxv}-acetic acid 'H >3MR {300 MHz, CDCI3) S 8.19 (d, IH), 8.09 (d, IH), 7.82 (d, IH), 7.78-7.65 (m, 2H), 7.75 (dd, IH), 7.31-26 (dd, IH), 7.18 (dd, IH), 7.05-6.92 (m, 4H), 5.20 (s. 2H), 4.26 (s, 2H), 4.23 (s, 2H), 4.15 (s, 2H), 2.12 (s, 3H); MS (ESI) 478,480 {M+H;CI)*. Prepared ftom (example 52). Example 4 lad i2-r3-(4-Chloro-quinolin-2-ylroethoxy>-phenoxvmethvl7-6-methyJ-Tjfaenoxy|-acetic acid 'H NMR (300 MHz, DMSO) 5 S.20 (dd, IH), 8.08 (d, IH), 7.91-7.74 (m, 3H), 7.24-7.15 (m, 3H), 7.01 (t, IH), 6.74 (t, IH), 6.66-6.59 (m, 2H), 5.32 (s, 2H), 5.12 (s, 3H), 4.43 (s, 2H), 2.24 (s, 3H); MS (ESI) 464 (M+H)"". Prepared from {2-[3-(4-ch]oro-qmnoIiii-2-ylmetboxy)' phenoxymelhyi]-6-methy]-phenoxy}-acetomtiile (example 39n). Example 4 lae |2-[3-(7-Chloro-quinolin-2-ylmethoxy>-phenoxvmethvl1-6-methvi-phenoxv>-aceticacid 'H NMR (300 MHz, DMSO) 5 8.42 (d, IH), 8.03-8.00 (m, 2H), 7.68-7.60 (m, 2H), 7.27-7.07 (m, 3H). 6.94 (t, IH), 6.70 (d, IH), 6.59 (dd, 2H), 5.31 (s, 2H), 5.18 (s, 2H), 2.20 (s, 3H); MS (ESI) 464 (M+H)"*. Prepared from {2-[3-(7-chIoro-quinolin-2-ylmethoxy)-phenoxymethyI]-6-methyl-phenoxy}-acetonitrile (example 39o). Example 41 af {2-r3- 'H NMR (300 MHz, CDCI3) 5 8.07 (t, 2H), 7.60 (d, IH), 7.36 (dd, IH), 7.27-7.24 (m, IH), 7.15 (d, IH), 7.05-7.00 (m, 3H). 6.79 (s. IH), 6.58 (d. IH), 6.49 (dd, IH), 5.31 (s, 2H), 5.U (s, 2H), 4.54 (s, 2H). 3.90 (s. 3H), 2.30 (s, 3H); MS (ESI) 460 (M+HV. Prepared from {2-[3-(6-methoxy-qiiinolin-2-ylmethoxy)-phenoxymeihyl]-6-meihy3-phenoxy}-acetoniirile (example 39p). Example 4lag f2-r4-Bron]0-3-('quinolin-2-ylmethoxv)-phenoxvinethvl1-6-methyl-phenoxv}-acetic acid 'H NMR (300 MHz, DMSO) 5 8.42 (d, IH), 8.00-7.97 (m, 2H), 7.79-7.70 (m, 2H), 7.63-7.58 (m, IH), 7.46 (d, IH), 7.20-7.13 (m, 2H). 6.99-6.95 (m, 2H), 6.59 (dd, IH), 5.42 (s, 2H). 5.17 (s, 2H), 4.30 (s, 2H), 2.22 (s, 3H); MS (ion spray) 508 (M+H)*. Prepared from ethyl {2-[4-bromo-3-(quinolin-2-ybnethoxy)-phenoxymethy]]-6-methyI-phenoxy}-acetate (example 54). Example 41 ah f2-r2-Bromo-5-('quinolin-2-vlroethoxv)-phenoxymelhyn-6-methyI-phenoxy}-aceticacid 'H NMR(300 MHz, CDCb) 6 8.18-8.15 (m, 2H), 7.S1-7.72 (m, 2H), 7.63-7-53 (m, 2H). 7.37 (d, IH), 7.28 (d, IH), 7.17-7.13 (m, IH), 7.09-7.03 (m, IH), 6.9l(d, IH), 6.42 (dd, 2H), 5.36 (s, 2H), 5.32 (s, 2H), 4.63 (s, 2H), 2.32 (s, 3H); MS (ion spray) 508 (M+H)*. Prepared from ethyl {2-[2-bromo-5-(quinolin-2-ylmeihoxy>phenoxyinethyl]-6-me^yl-phenDxy}-acetaie(exainpie 54). Example 4 lai f2-Metfavl-6-f3-methvl-5-(quinolin-2-vlmethQxy>-phenoxymethvl1-phenoxv>-aceticacid 'HNMR (300 MHz, CDCb) 5 8.2I-8.I4 (m, 2H), 7.82-7.66 (m, 3H), 7.58 (t, IH), 7.27-7.24 (m, IH), 7-17 (d, IH), 7.04 (t, IH), 6.60 (s, IH). 6.43 (s, IH), 6.37 (s, IH), 5.24 (s, 2H), 5.13 (s, 2H), 4.60 (s, 2H), 2.32 (s, 3H), 2-19 (s, 3H); MS (ion spray) 444 (M+Kf. Prepared from ethyl {2-methy!-6-[3-methy]-5-(quinoIin-2-yImethoxy)-phenoxyinethyl]-phenoxy}-acetaie (example 36j). Example 41aj a-l2-Acetyl-5-(quinplm-2-vlmethoxv)-phenoxvmethvn-6-methvl-phenoxv}-aceticac:id 'HNMR (300MHz, DMSO) 5 8.39 (d, IH), 8.00-7.96 (m, 2H), 7.76 (t, IH), 7.67-7.57 (m, 3H), 7.28 (d, IH). 7.14 (d. IH). 7.02-7.00 (m. 2H)- 6.69 (d. IH). 5.43 (s. 2H). 5.35 (s, 2H). 4.27 (s, 2H), 2.39 (s, 3H}. 2,23 (s, 3H); MS (ion spray) 472 (M+H)"'. Prepared from ethyl (2-[2-aceTyI-5-(quinoliii-2-ylmethoxy)-phenoxyrneihyi]-6-meihy]-phenoxy}-acetaie (example 59). Example 41 ak f4-Chloro-2-meihv]-6-r3-f2-pvridin-2-vl-eihoxy)-phenoxymethvn-phenoxv}-acetic acid 'H NMR (300 MHz, DMSO) 5 8.52 (d, IH), 7.73 (m, IH), 7.26 (m, 5H), 6.56 (m, 3H), 5.12 (s, 2H), 4.48 (s, 2H), 4.34 (t, 2H), 3.17 (t, 2H), 2.26 (s, 3}i). MS (ESI) 428 (M+H)\ Prepared from {4-chloro-2-methy i-6-[3-(2-pyridvn-2-yl-ethoxy)-phcnoxymethy I]-phenoxy > -acelonitrile (example 36k). Example 4 lal {2-p--pfaenQxvmethyl]-6-methvI-phenoxv}-aceticacid 'H NMR (300 MHz, DMSO) 6 8.48 (bs, IH), 7.12 (m, 1 IH), 5.14 (s, 2H), 4.46 (m,"4H), 2.26 (s, 3H). MS(ESI)419(M+H)'. Prepared from {2-[3-(benzooxa2ol-2-ylaminomethy!)-phenoxyniethyl]-6-raethyI-phenoxy}-acetonitriIe (example 35d). Example 41am f2-r3-(Ben200xazoI-2-vlaininomethyl)-phenoxvmethyn-4-chioro-6-meihvI-phenoxv|-acetic3cid 'H NMR (300 MHz, DMSO) 5 8.47 (bt, 1H). 7.28 (m, 5H), 7.02 (m, 5H), 5.14 Example 4 Ian {243-(4-ChlDro-qumo\m-2-ylmethoxvmethyl)-DhenDXvmethvl1-6-rne\hvl-phenoxv>-aceticacid 'HNMR(300 MHz, DMSO) 6 8.20 (d, IH), 8.05 (d, IH). 7.81 (m, 3H), 7.25 (m, 2H), 7.12 (m, IH), 7.00 (m, 4H), 5.2! (s, 2H), 4.77 (s, 2H), 4.62 (s, 2H), 4. ] 5 (s, 2H), 2.24 (s, 3H). MS (ESI) 478 (M+H)*. Prepared from {2-[3-(4-chloro-qmnolin-2-yimethoxymeihyl)-phenoxymethyl}-6-methyl-phenoxy}-acetoniiri]e (example 35e). Example 41 ao f2-f3-("6-Meifaoxv-qumoiin-2-vlmethoxvmelhvl)-phenoxvmethvlV6-methv]-phenoxv}-acetic acid 'HNMR{300MH2,CDa3)6 8.18(d, ]H),8.10(d, lH),7.64((t IH), 7.36 (m, 211), 7.26 (m, 3H), 7.12 (m, 2H), 6.98 (m, 2H). 5.24 (s, 2H), 4.73 (s, 2H), 4.69 (s, 2H), 4.62 (s, 2H), 3.93 (s, 3H), 2.38 (s, 3H). MS (ESI) 474 (M+Hf. Prepared from (2-[3-(6-metfaoxy-quinoIin-2-y]methoxymeihyi>phenoxymethy!]-6-methyI-phenoxy}-acetomtriIe (example 35f). Example 4lap (2-MethvI-6-r3-("quinolin-2-vlmeihoxvmetbv])-pheiioxYmethvl}-pheno?rv}-acetic acid 'H NMR (300 MHz, CDCI3) 5 8.30 (d, IH), 8.18 (d, IH), 7.85 (d, IH), 7.74 (m, 2H), 7.58 (m, IH), 7.38 (d, IH), 7.28 (m, 3H), 7.12 (m, IH), 6.99 (m, 2H), 5.24 (s, 2H), 4.78 (s, 2H). 4.71 (s, 2H), 4.63 (s, 2H), 239 (s, 3H). MS (ESI) 444 (M+H)*. Prepared from {2-methy!-6-[3-(qumoIin-2-ylme£hoxymethyl)-phenoxymethy]}-phenoxy}-acetonitrile (example 35g). Example 41 aq (2-Methyl-6-f3-fpYridm-4-vlmethoxv>-phenoxvmethvIl-phenoxv)-aceticacid 'HNMR (300 MHz, DMSO) 5 8.57 (bs, 2H), 7.44 (m. 2H), 7.22 (m, 3H), 7.07 (m, IH), 6.69 (m, IH),6.61 (m, 2H), 5.15 (s, 2H), 5.13 (s, IB), AM (s,2H), 2.27 (s, 3H). MS (ESI) 380 QA+Kf. Prepared from {2-methy]-6-[3-(pyridin-4-ylmethoxy)-phenoxymethyI}-phenoxy}-acetonitriie [example 39q). Example 4 lar f2-Methvl-6-f3-fDvridin-2-vlmethoxv)-phenoxvmethvn-phenoxvi-acetic acid HNMR (3O0 MHz, DMSO) 5 8.5S (bd, IH), 7.83 (m, IH), 7.50 (d, IH), 7.34 (ra, IH), 7.21 (m, ;H), 7.05 (m, IH), 6.64 (m, 3H), 5.14 (s, 4H), 4.38 (s, 2H). 2.26 (s, 3H). MS (ESI) 380 (M+H)^ Veparedfrom {2-methyl-6-[3-(pyridin-2-ylmethoxy)-phenoxymethyl]-phenoxy}-acetomtrile example 39r). Example 41 as ;2-Methvi-6-[3-(pvridin-5-vlmethoxvVphenox.vmethvn-phenoxvi-aceucacid 'H NMR (300 MHz. DMSO) 6 S.67 (s, IH). 8.55 (bd, IH), 7.86 (d, IH), 7.43 (m, IH), 7.28 (m, 3H), 7.07 (m, IH), 6.70 (s, lH),-6.62 (m, 2H), 5.13 (s, 4H), 4.47 (s, 2H), 2.27 (s, 3H). MS (ESI) 380 (M+H)*. Prepared from {2-rnethyi-6-[3-(pyridin-3-ylmethoxy)-phenoxyinethyI]-pbenoxy}-acelonitrile (example 39s). Example 41 at {2-r3-(6.7-Pichloro-quinolin-2-vlmethoXY>-phenoxvmethvn-6-methvl-phenoxv|-aceticacid 'HNMR (300MHz, DMSO) 5 8.44 (m, 2H), 8.30 (s, IH), 7.76 (d, IH), 7.22 (m, 3H), 7.04 (m, IH), 6.72 (m, IH), 6.63 (m, 2H), 5.35 (s, 2H), 5.13 (s, 2H), 4.46 (s, 2H), 2.26 (s, 3H). MS (ESI) 498 (M+H)**. Prepared from {2-[3-(6,7-dichloro-quinolin-2-yImethoxy)-phenoxymethyl]-6-methyl-phenoxy}-acetoiiitri]e (example 39t). Example 4 lau Ethvi 4-benzyioxv-2-r3-f2-carboxymethoxv-3-roethvl-beigvlQXV>-beTizvioyvV6-meth-vi-benzoate 'H NMR (300 MHz, DMSO) 6 7.31 (m, 8H), 7.06 (m, 2H), 6.96 (m, 2H), 6.65 (d, IH), 6.54 (d, IH), 5.12 (d, 6H). 4.48 (s, 2H), 4.22 (q, 2H), 2.28 (s, 3H), 2.19 (s, 3H), 1.21 (t, 3H). MS (ESI) 571 (M+H)*. Prepared from ethyl 4-benzyloxy-2-[3-(2-cyanomethoxy-3-methyI-benz>'loxy)-benzyloxy]-6-methy]-beiizoate (example 64b). Example 4lav 4-Beiizvloxv-2-i"3-f2-carboxvmethoxv-3-methvl-benzvlQXV>-benzvloxv1-6-methv]-benzoic acid 'H NMR (300 MHz, DMSO) 5 7.32 (m, 8H), 7.02 (m, 4H), 6.64 (d, IH), 6.52 (d, IH), 5.13 (m, 6H), 4.48 fs, 2H), 2.28 (s, 3H), 2.22 (s, 3H). MS (ESI) 543 (M+H)^. Prepared from ethyl 4-benz\'ioxy-2-[3-(2-carboxymethoxy-3-methyl-benzyloxy)-benzyloxy]-6-methyI-benzoate (example 41au). Example 41 aw {2-Methvl-6-r3--fl.3.3--trimethvl-2-Qxo-2.3-dihvdro-lH-mdQl-6-vlQxvmethv[VDhenoxvmethvn-phenoxvl-acetic acid 'H NMR (300 MHz, DMSO) 6 7.21 (m, 5H), 6.99 {m, 3H), 6.75 (d, IH), 6.64 (dd, IH), 5.24 (s, 2H), 5.07 (s, 2H), 4.12 (s, 2H), 5.10 (s, 3HX 2.25 (s, 3H), 1.21 (s, 6H). MS (ESI) 476 (M+H)*. Prepared from {2-methyl-6-[3-(1.33-trimethyl-2-oxo-2,3-dihydro-lH-indol-6-yioxj'methyI)- phenDxymethyl]-phenoxy}-aceionitrile (example 64c). Example 4 lax 7-f3-(qmnotin-2-vIinethDXV>-pbenoxviT)elhvn-beii2Dfuian-2-caTboxylic^d 'HNMR (300 MHz, CD3OD) d 8.36 (dd, IH), 8.03 (dd, IH), 7.94 (dd, IH), 7.61-7.78 (m, 4H>, 7.45-7.49 (m, 2H), 7.16-7.29 (m. 2H), 6.77 (s, IH), 6.67 (dt, 2H), 5.42 (s, 2H), 5.32 (s, 2H); MS (ESI) 426 (M+H)*. Prepared from ethyl 7-[3-(qumolin-2-yimethoxy>phenoxymetfayl]-ben2ofuran-2-carboxylate (example 36i). Example 4 lay {2-Methvl-6-[3-f2-phenyl-thiazol-4-vlroefliDxy>-phenoxvmethvl"l-pheDoxy>-aceticacid. ^H NMR (300 MHz, DMSO): 5 7.92 (m, 2H), 7.77 (s, IH), 7.47 {m, 3H). 7.20 (m, IH), 7.15 (m, 2H), 6.98 (t, IH), 6.72 (t, !H), 6.60 (m, 2H), 5.15 (s. 2H), 5.14 (s, 2H). 4.15 (s, 2H), 2.23 (s, 3H); MS (ESI) 462 (M+H)^. Prepared from {2-methy!-6-[3-(2-phenyl-thiazol-4-ylmethoxy)-phenoxymethyI]-phenoxy}-acetomtrile (example 39u). Example 42 f4-Ch]oro-2,6-dimeThvI-phenoxv)-acetonitrile 4-Chloro-2,6-dimeihyIphenoI (5.0 g, 32 mmol), bromoacetonitrile (2.2 mL. 32 mmol) and potassium carbonate (6.6 g, 48 mmol) are combined with acetone (50 mL) and heated at reflux for ] 8 h. The reaction is filtered, concentrated and the residue partitioned between dichloromethane and water. The organic phase is washed with IN HCi and water and is then dried over magnesium sulfate, concentrated and purified by column chromatoeraphy (silica, 10% sthyl acetate in hexanes) to provide the title compound. MS (EI) 195 (M)", CI pattern. Example 42a 2-tert-Butvl-6-methylphenoxv)-acetonitrile rhe title compound is prepared using essentially the same procedure used in example 42 except ising 2-iert-buty]-6-methylphenol in place of 4-chJoro-2,6-dimethylphenol.MS (EI) 203 (M+)*. Lxampie 42b ithyl f2.6-dimethyi-phenoxv)-acetate "he title compoimd is prepared using essentially the same procedure used in example 42 except sing 2,6-dimethylphenol in place of 4-chloro-2,6-dimethylphenoI and ethyl bromoacetatc in lace of bromoacetonitrile. ixample 43 i-Bromomethvl-4-chloro-6-methvl-phenoxy)-acetonitriIe ^Chlo^o-2,6-dimethyI-phenoxy)-acetonitrile (700 mg, 3-6 mmol, example 42), N-romosuccinimide (510 mg, 2.9 mmol) and benzoyl peroxide (72 mg, 0.29 mmol) are heated at :flux in carbon tetrachloride (10 mL) for 16h. The reaction is cooled, filtered and the filtrate is mcentrated and purified by column chromatograpy (silica, 5% ethyl acetate in hexanes) to rovide the title compound. MS (EI) 273 , 275(1^1)", Br pattern. i he following compounds are prepared using essentially the same procedure used in example 43 except using the cited methyl analog in place of (4-chloro-2,6-dimethyl-phenoxy)-acetonitriie. Example 43a f2-Bromomethvl-6-tert-butyl phenoxv)-acetonitrile MS (EI) 281 (M+)*. Prepared from (2-ieit-butyl-6-methylphenoxy)-acetomtrile (example 42a). Example 43b Ethvl (2-bromomeihyi-6-meihvi-Dhenoxv>-acetaie Prepared from ethyl (2,6-dimethyl-phenoxy)-acetaie (example-42b). Example 44 5-Chloro-2-hyciroxy-3-methoxv-benzaldehvde A solution ofsulfiiryl chloride (15 mL, 190 mmol) in toluene (20 mL) is added dropwise over 1.5 h to a solution of o-vanillin (25.0 g, 164 mmol) in toluene (90 mL) and the reaction is then stirred 16 h. Water (30 mL) is added over 10 minutes with ice-bath cooling. The solid is filtered, washed with water and dried to provide the title compound. MS (EI) 186 (M)*. Example 45 4-Chloro-2-methvl-l-oxo-quinoline mCPBA 70% pure (6.9 g, 29 mmol) is added to a solution of 4-chloroquinaldine (5.1 g, 29 mmol) in dichloroethane and heated to 50 °C for 4 h. The reaction is concentrated and partitioned between ethyl acetate and aqueous potassium carbonate. The organic phase is washed with additional aqueous potassium carbonate, water and is liisn dried over magnesium sulfate. The solution is filtered and concentrated to yield the title compoimd which is used without further purification. MS (ESI) 194 (M+H)*. I The following compounds are prepared using essentially the same procedure used in example 45 except using the cited quinaidine in place of 4-chloroquinaIdine. Example 45a 7-Chloro-2-methyl-1 -oxo-quinoline MS (ESI) 194 (M+H)*. Prepared firom 7-chioroquinaldine. Example 45b 6-Methoxv-2-methvJ-]-oxo-quinoline MS (ESI) 190 (M+H)*. Prepared from 6-methoxyquinaidine. Example 45c 5-ethvI-2-methvl-pyridine 1 -oxide MS (ESI) 138 (M+H)*. Prepared from 5-ethy]-2-methylpyridine. Example 46 4-Chioroouinplin-2-vlmethyI chloride 4-Chloro-2-methyl-l-oxo-quinoline (4.3 g, 22 mmoi) is dissolved in chloroform (200 mL) and p-toluenesulfonyl chloride (3.7 g, 20 mmol) is added and the reaction is healed at 65 "C for 24 h. The reaction is allowed to cool and then concentrated and partitioned between ethyl acetate and 10% aqueous potassium carbonate. The organic phase is dried over magnesium sulfate, concentrated and purified by column chromatography (silica, 60% dichloromethane in hexanes) to provide the title compound. MS (ESI) 212 (M+H)*. The following compounds are prepared using essentially the same jwocedure used in example 45 except using the cited quinaldine in place of 4-chloroquinaldine. Example 46a 7-Chloroquinolin-2-vlmethvI chloride MS (ESI) 212 (M+H)*. Prepared from 7-chloro-2-methyl-l-oxo-qumoiine (example 45a). Example 46b 6-Methoxyquinolin-2-yimethyl chloride MS (ESI) 208 (M+H)*. Prepared from 6-methoxy-2-methy!-l-oxo-quinoIine (example 45b). Example 47 2-{3-?5-Chioro-3-mEthvl-2-(lH-tetrazDl-5-vlmethoxv>-benzvloxvVt?hgnoxvmethvU-quinoline Sodium azide (395 mg, 6.1 mmol) and ammonium cWoride (325 mg, 6.1 mmol) are added to a solution of {4-chloro-2-methyl-6-[3-(quinoiin-2-yimethoxy)-phenoxymethy!3-phenDxy}-acetonitrile (300 mg, 0.68 mmol. example 36c) in DMF (2 mL) and healed at UO 'C for 2 h. The reaction is then cooled and poured into a 1 N sodium hydroxide solution (20 mL) with the formation of a solid. This mixture is then washed with ether (^x) and the ether is discarded. The remaining aqueous solution contains a solid which is filtered. This solid is dissolved in \ 0% eihanol water (250 mL) and the pH is lowered to about 5 with 2N HC!. A solid precipitates which is filtered to provide the title compound. m.p. 181-184 "C; 'HNMR(300MH2, DMSO-d,) d 8.40 (d !H), 8.01-7.97 (m, 2H), 7.77 (dd, ]H), 7.66-7.60 (m, 2H), 7.33 (d, 2H), 7.18 (dd, IK), 6.72 (dd, IH), 6.65 (dd, IH), 6.59 (dd, IH), 5.33 (s, 2H), 5.27 (s, 2H), 5.07 (s, 2H), 2:24 (s, 3H); MS (ESI) 488, 490 (M+H;CI)^ Example 48 |^3-(OuinoHn-2-vlmethoxv>-phenvn-methanol 2-Chloromethylquinoline hydrochloride (U.6 g, 54 mmoi), 3-hj'droxyben2yi alcohol (6.7 g, 54 mmol) and potassium carbonate (16 g, 116 raraol) are heated in DMF (45 mL) at 50 "C for 14 h. The temperature is increasesd to 80 "C and heated an additional 24 h. The reaction is cooled and added to water, filtered and the solid is washed with water to yield a semi-pme product. The residue is dissolved in ethyl acetate, dried over magnesium sulfate, filtered and concentrated. The sample is then recrystallized from ethyl acetate and hexanes to provide the title compound. MS (ESI) 266 (M+H)"". Example 49 2-(3-Chloromethvl-phenoxvmethvl)-quinoline hydrochloride Thionyl chloride (0.95 mL, 13 mmol) is added to a solution of [3-(quinDlin-2-yhnethoxy)-phenylj-methanol (2.9 g, 11 nmiol, example 48) in dichlorometbane (30 mL) and allowed to stir 18 h. The reaction is concentrated in vacua and azeotroped twice &om chlorofonn to yield the title compound which is used without further purification. Example 50 2 -[3 -f Ouinolin-2-vlmethoxv)-benzvl oxv 1-6-tri fluoromethvl-benzaldehvde [3-(Quinolin-2-ylmethoxy)-phenyl]-methanol (300 mg, 1.13 mmol, example 48) is dissolved in DMF (6 tnL) and sodium hydride (60%, 60 mg, 1,5 mmol) is added and allowed to stir 20 rain. 2-Fiuoro-6-('trifluoromethynbenzaldehyde (0.30 mL, 2.2 mmoi) is added and the reaction is heated at 90 °C for 5 h. The reaction is panitioned between ethyl acetate (200 mL) and water (200 mL), dried over magnesium sulfate, fihered. concentrated in vacuo and purified by column chromatography (silica, 25% ethyl acetate in hexanes) to provide the title compound; MS (ESI) 438 (M+H)^ Example 51 2-n"(OuinoHn-2-vlmelhDXYVbeiizylDxy1-6-trifluoromethvl-benzoic ^d A solution of 2-[3-(quinoIb-2-yImelhoxy)-ben2ylDxy]-6-trifluoromethyi-benzaldehyde (46 mg, 0.1 mmol, example 50) in 2-methyI-2-butene (I mL), t-butanol (2 mL) and water (2 mL) is treated with sodium dihydrogenphosphate dihydrate (153 mg, 1.1 mmol) and sodium chlorite (198 mg, 2.2 mmol). After 45 min. the reaction is partioned between dichloromethane (50 mL) and water (50 mL). The organic layer is dried over magnesium sulfate, filtered and concentrated m vacuo to provide the title compound: m.p. 184-185 "C; 'HNMR(300 MHz, CDCl3)5 8^8 (d, IH), 8.12 (d, IH), 7.82-7.75 (m, 2H), 7.66-7.55 (m, 2H), 7.42 (dd, IH), 7.30-7.27 (m, 2H), 7.16 (d, IH), 7.07 (dd, IH), 6.88 (d, IH), 6.77 (dd, IH), 5.44 (s, 2H), 5.07 (s. 2H); MS (ESI)454 (M+H)". Example 52 (4-ChlDrQ-2-methyl-6-r3-(quinolin-2-vlmetiiQXv)-benzvloxvmethvn-phenoxy>-acetonitrile p-(Quinolin-2-yImethoxy)-phenyl]-methanoI (190 mg, 0.72 mmol, example 48) is dissolved in DMF (6 mL) and sodium hydride (60%, 30 mg, 0.75 mmol) is added and allowed to stir for 10 min. (2-Bromomcthyl-4-chIoro-6-methyl-phenoxy)-acetonitriIe (210 mg, 0.78 mmol, example 43) is added and the reaction is allowed to stir 6 h. The reaction is partitioned between ethyl acetate and water and the organic phase is washed with additional water. The organic phase is dried, concentrated and purified by column chromatography (silica, 25 % ethyl acetate in hexanes) to provide the title compound. MS (ESI) 458 (M+HT, CI pattern. Example 53 Methvl2-methvl-6-[3-(quinolin-2-vlmethoxvVbenzvtoxvmethvn-benzoatg The title compound is prE^ared using essemially the same procedure used in example 52 except using methyl 2-bromometi:\yl-6-methyl-ben2oate (example 2) in place of (2-brQmomeihy(-4-chloro-6-methyl-phenoxy}-aceionitrile. MS (ESI) 427 (M+H)*. Example 54 Ethyl i2-y4-bromo-3-fquinolin-2-vtmethoxvVphenoxvmethvn-6-methyI-phenQxy|-acetateand Ethyl {2-F2-bromo-5-(qmnolin-2-vlmethoxv)-phenoxvmethvt'l-6-methvl-phenoxv^-acetate Ethyl {2-methyl-6-[3-(quinoIin-2-ylmethoxy)-phenoxymethy]]-phenoxy}-acetate (350 mg, 0.76 nimol, example 36h),NBS (150 mg, 0.84) and benzoyl peroxide (20 mg, 0.08 mmoOare dissolved/suspended in chJoroform (7 mL) and heated to reflux for 2 hrs. The reaction is cooled to r.t., filtered, preadsorbed onto silica gel by rotary evaporation. The crude material is purified by flash chromalography (silica, 15% ethyl acetate in hexanes) to give the title compounds in approximately 3 1:1 ratio. RegJoisomers are determined by NMRNOE data, MS(ionspray) 537 (M+H)* for both compounds. Example 55 3-Metfayl-5-fquinolin-2-vlnifethoxv)-phenoI 2-(ChlorDmethyI)-quino]ine hydrochloride (1.28 g, 6.0 mmol), orcinol (568 mg, 4.0 mmol), KJCOB (1.68 g, 12.0 mmol) and a catalytic amount of tetrabutylammonium iodide (- 10ing>aie dissolved/suspended in anhyd. DMF (10 mL) and heated at 50 "C overnight The reaction is cooled to r.t. and partitioned between water (100 mL) and ethyl ether (100 mL). Tlie pH of the aqueous layer is adjusted to - 5 and flirther extracted with ethyl ether (1(K) mL). The organic fractions are pooled and washed with brine (2 x 100 mL), dried over MgS04, filtered and preadsorbed onto silica gel. The crude preadsorbed material is purified by flash chromatography (silica, 20% ethyl acetate in hexanes) to give die title compound. This product (approx. 80% purity, remainder is 2'melhylquinoiine) is used without fiirther purification. MS (ESI) 266 (M+H)^. Example 56 2-r3- 2-(3-Ch]oromethy]-phenDxymethyl)-quinoIine (371 mg, 1.3 mmoi, example 49) and saiicylaldehyde (133 }iL, 1.25 mmol) are dissolved in acetone (iO mL). K3CO3 (525 mg, 3.75 mmol) is added and the contents are healed to reflux for 16 hrs. The reaction is cooled to r.L, poured into water (100 mL) and.extracted with ethy! ether (3 x 50 mL). The ether layers are combined and washed with Brine (3 x 75 mL) and dried over MgS04. The crude material is preadsorbed onto silica gel and purified by flash chromatography (silica, 20 to 25% ethyl acetate in hexanes) to give the title compound. MS (ion spray) 370 (M+H)"'. Example 57 3-{2-r3-(Quinolin-2-vlmethoxv)-benzvIoxy1-phenvU-acrvIic acid 2-[3-(QuinoIin-2-ylmethQxy)-benzyloxy]-benzaldefayde (UO mg, 0-3 mmol, example 56) is dissolved in pyridine (1 mL). Malonicacid (63 mg, 0.6 mmol)andpiperidine(10 pL, 0.1 mmol) are added and the contents are heated to 85 °C for 2 hrs, then at II0 °C for another 2 hrs. The reaction is cooled and placed under a nitrogen stream at 40 *C to remove the pyridine. A small amount of toluene is added and the contents are again placed imder a nitrogen stream at 40 "C (repeat). The crude material is purified on silica gel by flash chromatography (silica, 2.5% methanol in dichloromethane) to give the title compound. 'H NMR (300 MH2, CDCI3) 5 8.33 (d, IH), 8.21-8.16 (m, 2H), 7.81-7.70 (m, 3H), 7.56-7.50 (m, 2H), 7.37-7.25 (m, 3H), 7.03-6.93 (m, 4H), 6.50 (d, IH). 5.48 (s, 2H), 5.14 (s, 2H); MS (ion spray) 412 (M+H)Example 58 I-r2-Hvdroyv-4- 2\4'-Dihydroxy-acetophenone (912 mg, 6 nmiol) and 2-chloromethyl-qiiinoline hydrochloride (856 mg, 4.0 mmol, example 49) are dissolved in acetonitrile (20 mL). K2CO3 (1.12 g, 8.0 mmol) is added and the contents are heated to 50 "C for 16 hrs. The reaction is cooled to room temperature, and the solvent is removed by rotary evaporation. The contents are partitioned between eihyl acetate (100 mL) and water (100 mL), the aqueous layer is acidified with 2 N HC! to ~ pH 2 and further extracted with ethyl acetate (2 x 50 mL). All organic fractions are combined and washed with brine (3x150 mL), dried over MgSOl and concentrated. The crude material is preadsorbed onto silica gel and purified by flash chrornatography (silica, 15% ethyl acetate in hexanes) 10 give the title compound; MS (ion spray) 294 (M+H)~- Example 59 Etfav! f2-|"2-acetvI-5-fquinoiin-2-vlmethox"v')-phenoxvinethvn-6-methvl-phenoxv>-acetate 1 -[2-Hydroxy-4-(qumolin-2-ylmethoxy)-phenyl]-ethanone (] 85 mg, 0.63 mmol, example 58) is dissolved in 2:1 DMF/acetomtrile (6 mL). Ethyl (2-bromoinethyl-6-methyl-phenoxy>acetate (272 mg, 0.95 nunoi, example 43b) and K2CO3 (177 mg, 1.26 mmol) are added and the contents are heated to 50 °C for 2 days. The reaction is cooled to r.L and the volume reduced under a nitrogen stream at 40 "C. The contents are partitioned between ethyl acetate (50 mL) and water (50 mL). The aqueous layer is further extracted with ethyl acetate (2 x 50 mL). The organic fractions are combined and washed with brine (3 x 75 mL), dried over MgS04 and concentrated. The crude material is dissolved in I; 1 dichloromethane/methanol, preadsorbed onto silica gel, and purified by flash chromatography (silica, 20% ethyl acetate in hexanes) to give the title compound. MS (ion spray) 500 (M+H) *. Example 60 Methyl 2-p-fauinoiin-2-vlmethoxv)-benzvloxy "I-benzoate The &ee base of 2-(3-chloromethyl-phenoxymethyI)-quinoline hydrochloride (540 mg, 1.7 mmol, example 49) is prepaid by partioning the material between ethyl ether and sodium bicarbonate and drying the organic phase with magnesiimi sulfate. This material is then dissolved with methyl salicylate (260 mg, 1.7 mmol) in DMF (10 mL) at 0 °C and sodium hydride (60%, 65 mg 1.7 mmol) is added. The reaction is brought to room temperature for 15 min. and is then heated at 60 "C for 6 h. The reaction is cooled and pardoned between ethyl acetate and a saturated ammonium chloride solution. The organic phase is dried over magnesiiun sulfate, filtered, concentrated in vacuo and purified by column chromatography (silica, 50 to 80 % ether in hexanes) to provide the title compound; MS (ESI) 400 (M+Pf)*. The following compounds are prepared using essentially the same procedure used in example 60 except using the cited substituted salicylate in place of methyl salicylate. Example 60a Methvl 3-methoxv-2-r3-rauinolin-2-vlm£thoxv'i-benzvloxy1-ben2oate Prepared from methyl 3-methoxysalicylate. Example 60b Methvl 4-methQxv-2-r3-('QuinoIin-2-ytmethQxv)-benzv]oxv'l-berLZoate Prepared from methyl 4-methoxysalicylate. Example 60c Methvl 5-methoxv~2-|"3-fquinoHn-2-vlmetboyv>-benzvloxv1-benzoate Prepared from methyl 5-methoxysaIicylate. Example 60d Methyl 2-methoxy-6-r3-(qumoIin-2-vlmethoxv>benzvloxvVl)enzoate Prepared from methyl 6-methoxysalicylate (example 61). Example 60e Ethyl 2-methyl-6-F3-(ouinoHn-2-vlmethpxvVbeiizvloxvVbeii2oate MS (ESI) 428 (M+H)". Prepared from ethyl 6-methylsalicylate (See, Hauser, Frank M., Synthesis 1980, JO, 814-15. Example 61 Methvl 6-methoxvsaIicvlate A mixture of 6-methoxysalicylic acid (10.0 g, 59.5 mmol) in methanol (40 mL) and sulfuric acid (2 mL) is heated at reflux 48 h. Although some acid remains the reaction is concentrated to remove the methanol and partitioned between ethyl acetate and saturated sodium carbonate solution. The organic phase is separated and vrashed with sodium carbonate until no acid remains by TLC analysis. The organic phase is dried and concentrated to provide the title compound as a low melting solid. Hxampie 62 Methyl 5-r3-(quinQiin-2-vlmethoxvVbenzvlQxv1-nicotinat£ To a solution of 5-hydroxy nicotinic acid methyl ester (200 mg, 1.3 mmoi) in DMF (3 mL) is' added 60% sodium hydride emulsion (50 mg, 1.2 mmol) and this mixture is stirred 30 minutes. The free base of 2-(3-chloromethyl-phenoxymethyi)-quinoiine hydrochloride (350 mg, 1.2 mmol, example 49} is prepard by partioning the material between ethyl ether and sodium bicarbonate and drying the organic phase with magnesium sulfate. A solution of this free base in DMF (2 mL) is added to the alcohol and this mixture is stirred at 25 °C for 16 hours. The solvent is removed in vacuo, dichloromethane (10 mL) and water (5 mL) is added, and this mixture is acidified to pH6 with acetic acid. The organic layer is dried over magnesium sulfate and the solvent removed in vacuo. The residue is purified by flash chromaiogr^hy (silica, 4% methanol in dichloromelhane) to give the tide compound. MS (ESI) 401 (M+H)*. Example 63 Ethyl 4-benzvloxv-2-hvdroxv-6-methvl-benzoate To a solution of ethyl-2,4-dihydroxy-6-methyi benzoate (4.22 g, 22 mmol) in acetone (80 mL) is added potassiimi carbonate (3.0 g, 22 mmol) and benzyl bromide (2.6 mL, 22 nunol) and this mixture is heated under reflux overnight. The cooled reaction is diluted with ethyl acetate (100 mL) and water (100 mL) and the organic layer washed with water (2 x 80 mL) and brine (2 x 80 mL). Tbe organic iayer is dried over m^nesium sulfate and the solvent removed lo provide the title compound without fiirther purification. MS (EI) 286 (M)"^. Example 63 a Ethyl 2-hydroxv-4methoxv-6-methvl-ben2oate The title compound is prepared using essentially the same procedure used in example 63 except using iodomethane in place of benzyl bromide. Example 64 Ethvl4-benzv]oxvr2-methyl-6-r3-fqmnoiin-2-vlmethoxvVbenzvloxv1-benzoate To a soluiion of ethyl 4-ben2yloxy-2-hydroxy-6-methy!-ben2oats (5.1 g, 16 mmoi. example 63) in DMF (3 00 mL), with 25 °C waier baih cooling, is added 60% sodium hydride emuision (1.3 g. 32 mmoI) over 2 minutes. This mixiure is stirred 30 minutes with the cooling bath removed. A solution of 3-(quinoIin-2-yimethoxy)-benzyI chloride hydrochloride (5.1g, 16 nunol, example 49), in DMF (55 mL) is added and the reaction heated at 60 °C for 6 hours. The solvent is removed in vacuo and the residue purified by flash chromatography (silica, 0.5 to 2% methanol in dichloromethane) to give the title compound. MS (ESI) 534 (M+H)'. Example 64a Ethvt 4-methQxv-2-methvl-6-f3-(quinolin-2-vlmethoxvVbengvloxvl-berizoate The title compoimd is prepared using essentially the same procedure used in example 64 except using ethyl 2-hydroxy-4methoxy-6-methyl-ben2oate (example 63a) in place of ethyl 4-benzyloxy-2-hydrDxy-6-methyl-benzoate. MS (ESI) 458 (M+Hf. Example 64b Ethyl 4-benzvioxv-2-r3-("2-cvanomeihQXv-3-methyl-benzvloxy>-faenzvloxvl-6-methyI-ben2oate The title compoimd is prepared using essentially the same procedure used in example 64 except using [2-(3-brDmomethyl-phenoxymethy])-6-melhyl-phenoxy]-acetonitrile (example 76) in place of 3-(quinolin.2-ylmethoxy)-benzyl chloride hydrochloride. ^H NMR (300 MHz, CDCI3) 5 7.30 (m, 8H), 7.12 (m, IH), 7.06 (bs, IH), 6.99 (d, IH). 6.90 (dd, IH), 6.42 (s, 2H),-5.07 (s, 2H), 5.04 (s, 2H), 5.02 (s, 2H), 4.71 (s, 2H), 4.33 (q, 2H), 2.39 (s, 3H), 2.30 (s, 3H), 1.31 (t, 3H). MS (ESI) 552 (M+H)*. Example 64c f2-Methvl-6-[3-f].3.3-trimethvl-2-oxo-2.3-dihvdro-lH-indoI-^vloxvmethvi")-phenoxvmethyl1- phenox V} -acetonitri le The title compound is prepared using essentially the same procedure used in example 64 except using [2-(3-bromomethyI-phenoxymethy])-6-raethyl-phenox>']-acetonitrile (example 76) in place of 3-(quino!in-2-ylmethoxy)-ben2yI chloride hydrochloride and 6-hydroxy-L3,3-trimethyl-U3-dihydro-indoI-2-one (example 80) in place of ethyl 4-benzyloxy-2-hydroxy-6-methyl-benzoate. 'H NMR (300 MHz. CDCI3) 5 7.32 (dd, 2H), 7.24 (s, IH), 7.M (m, 4H), 6.96 (dd, IH), 6.62 (dd. IH), 6.54 (i IH), 5.10 (s, 2H), 5.06 (s, 2H), 4.72 (s, 2H), 3.18 (s, 3K), 2.39 (s, 3H), 1.34 (s, 6H). MS (ESI) 457 (M+H)*. Example 65 Ethvl 2-hvdroxv-6-methvl-4-i"3-('qumoIin-2-vlmethoxv>-benzvloxv1-benzoate 2,4-Dihydroxy-6-melhyl-beiizoic acid ethyl ester (315 mg, 1.6 mmol) is combined with 2-(3-chJoromethyl-phenoxymetbyO-quinoline hydrochloride (0.51 g, 1.6 mmol, example 49), tetrabutylammonium iodide (55 mg, 0.15 mmol) and potassium carbonate (0.48 g, 3.5 mmol) in acetone (9 mL). The reaction is heated at reflux 48 h. The reaction is partitioned between ethyl acetate and saturated ammonium chloride. The organic phase is washed with brine, dried over magnesitmi sulfate, filtered and concentrated to yield the crude product. This material is purified by column chromatography (silica, 3% ether in dichloTomethane) to the title compotmd; m.p. 127-128 °C, MS (ESI) 444 (M+H)*- Example 66 Ethyl 2-roethoxv-6-methvl-4-r3-fqtiinolin-2-vlmethoxv)-benzvloxvl-ben2oate To a solution of ethyl 2-hydroxy-6-methyl^[3-(quinolin-2-ylmethoxy)-benzyioxy]-ben2oate (150 mg, 0.34 mmol, example 65) in DMF (5 mL) is added sodium hydride (60%, 14 mg, 0.34 mmol) and the reaction is stirred 20 min. lodomethane (0.03 mL, 0.5 mmol) is added and the reaction is heated at 50 'C for 7 h. The reaction is concentrated in vacuo and the residue is paitioned between dichloromethane and aqueous ammonium chloride. The water layer Is back-extracted with dichloromethane, the organic phases are combined, dried over magnesium sulfate, filtered and concentrated to yield crude product The residue is purified by colunm chromatography (silica, 10 to 20% ethyl acetate in hexanes to provide the title compound; MS (ESr)458(M+H)^ Example 66a Ethvl 2-benzvloxv-6-methvi-4-I3-(omnolin-2-vlmethoxvV-benzvloxvVben2Date The title compound is prepared using essentially the same procedure used in example 66 except using benzyl bromide in place of iodomethane. MS (ESI) 534 (M+H) *. Example 67 4-Benzvloxv-2-methvl-6-f3-("quinolin-2-ylmethoxv')-benzvioxv")-ben2oicacid Ethyl 4-benzyIoxy-2-methyl-6-[3-(qiiiiioIin-2-ylmethoxy)-benzyloxy)-ben2oate (2.4 g, 4.5 mmole, example 64) is added to elhanol (50 mi) and ION sodium hydroxide (4.4 ml, 44 mmole) and refluxed for 8 hours. The solvent is removed in vacuo and the residue is dissolved in dichloromethane with a small amount of water and is acidified to pH6 with IN HCl. The organic layer is dried over MgSO* and the solvent removed in vacuo. The crude product is purified by column chromatography (silica, I % methanol in dichloromethane) to provide the title compound. m.p. 146-149'C; 'H NMR (300 MHz, CD3OD) d 8.34 (d, IH), 8.04 (d, IH), 7.91 (d. IH), 7.78-7.70 (m, 2H), 7.61 (t, H), 7.37-7.20 (m, 7H), 7-05-6.91 (m, 2H), 6.51 (d. IH), 6.47 (d, IH), 5.35 (s, 2H), 5.09 (s, 2H), 5.03 (s, 2H), 2.29 (s, 3H); MS (ESI) 506 (M+H)*. The following compounds are prepared using essentially the same procedure used in example 67 except using the cited ester in place of ethyl 4-benzyloxy-2-methyl-6-[3-(quinolin-2-ylinethoxy)-benzyloxy]-benzDate. Example 67a 2-Methoxy-6-methvI-4-[3-(quinQlin-2-vlniethoxy)-faenzvIoxv1-benzoicacid 'H NMR (300 MHz, CDCI3) 5 8.38 (d, IH), 8.03 (d, IH), 7.79 (d.,H), 7.70-7.67 (m, 2H), 7.61 (t, H), 7.28 (t, IH), 7.14 (s, IH), 7.01 (t, 2H), 6.35 (l. 2H), 5.37 (s, 2H), 5.03 (s, 2H), 3.71 (s, 3H), 2.26 (s, 3H); MS (ESI) 430 (M-KH)*. Prepared from ethyl 2-methoxy-6-methyl-4-[3-(quinolJn-2-yImethoxy)-benzyloxy]-benzoate (example 66). Example 67b 2 -Ben2rvloxv-6-methv] ^-f3-fquino 1 in-2-ylmethoxv>-ben2:v loxv1 -benzoi c acid 125-127 °C; 'H NMR (300 MHz, CDCI3) 5 8.18 (d, IH), 7.83 (d, iH), 7.74-7.55 (m, 3H), 7.40 (s, 5H), 7.39-7.29 (m, IH). 7.09 (s, IH), 7.00 {m. 2H). 6.50 (s. 2H). 5.41 (s, 2H). 5.13 (s, 2H), 5.04 {s. 2H), 2.58 (s, 3H); MS (ESI) 506 (M+H)'. Prepared from ethyi 2-benzyloxy-6-raeihyl-4-[3-(quinoiin-2-yimethoxy)-beazyloxy]-benzoate (example 66a). Example 67c 4-Methoxv-2-meihvl-6-f3-(quinoIin-2-vImethoxv>-benzv[Qxy1-benzQtc acid 'H NMR (300 MHz, DMSO) S 8.39 (d, IH), 8.02-7.96 (m, 2H), 7.79-7.74 (tn, IH), 7.67-7.57 (ra, 2H), 7.31-7.25 (m, IH), 7.16 (s, IH), 7.02-6.96 (m, 2H), 6.49 (s, IH), 6.39 (s, IH), 5.34 (s, 2H), 5.09 (s, 2H), 3.71 (s, 2H), 2.20 (s, 3H); MS (ESI) 429 (M+H)"". Prepared from ethyl 4-methoxy-2-methyl-6r[3-(quinolm-2-ylmethoxy)-benzyloxy]-benzoate (example 64a). Example 68 5-ethvl-2-chlorQmethyl pyridine To a solution of 5-ethyl-2-methyi-pyridine-l-oxide (427 mg, 3.11 mmol, example 45c) in CH2CI2 (2 mL) is atkied a solution (0.2 mL) of phosphorous (v) trichloride oxide (327 jiL) in CH2CI2 (2 mL). Added simultaneously the remaining phosphorous (v) trichloride oxide solution and a solution of triethylamine (4S8 ^lL) in CH2CI2 (2 mL) at such a rate as to niaintain a reSux. After the addition is complete, let reaction mixture cool to 20 °C and diluted with EtOAc. The organic layer is washed with sat. NaHCOj soln., brine, dried over MgS04 and concentrated. The residue is purified by flash chromatography (silica, 10% ethyl acetate in dichloromethane) to provide the tiUe compound MS (ESI) 156 QA+Hf. Example 69 2-(5-Ethvl-pvridin-2-vI')-ethanol To a cooled solution (-lO^C) of diisopropylamine (2.31 mL. I6.5raL) in THE ( 45 mL) is added dropwise (2.5M) n-butyilithium (6.6 mL, 16.5 mmol), let stiri 0 rain, then cooled to -7?°C. To this mixture is added dropwise a solution of 5-ethyl-2-methyIpyridine (1.98 mL, 15 mmol) in THE (3 mL) and let stir for 1 Omin at -78°C. To the reaction mixture is added paraformaldehyde (1.13 g. 37.5 mmol), the cold bath removed and stirring continued for 1 hr. Quenched reaction with H2O, diluted with EtOAc and the organic layer washed with brine, dried over MgSOi and concentrated. The residue is purified by flash chromaiography (silica. 0.5% ammonia / 5% methanol / dichloromethane) to give the title compound as a pale yellow oil. MS (EI) !5I (M)* Example 69a 2-quinolin-2-vl-ethano] The title compound is prepared using esseniially the same procedure used in example 69 except using 2-methyl-quinoline in place of 5-ethyl-2-methylpyridine. MS (ESI) 174 (M+H)"". Example 70 Benzoic acid 3-r2-f5-ethvl-pvridin-2-vl)-ethoxv1-phenvl ester To a solution of 2-(5-ethyl-pyridm-2-yI)-ethanoI (480 mg, 3-17 mmol, example 69) in THF (10 mL) is added resorcinol monobenzoate (630 mg, 2.94 mmol), triphenylphosphine (850 mg, 3^4 mmol) and diethyl azodicarboxylate (510 p.L, 3.24 mmol). The resulting mixture is stirred for I h then concentrated. The residue is purified by flash cliromaiography (silica, 35% ethyl acetate in hexane) to give the title compound as a yellow oil. MS (ESI) 348 (M+H)"^. Example 70a Benzoic acid 3-(2-Dvridin-2-vl-ethoxv)-phenvl ester The title compound is prepared using essentially the same procedure used in example 70 except using 2-(2-hydroxyethyi)pyridine in place of 2-(5-ethy!-pyrid:n-2-yl)-ethanol. MS (ESI) 320 (M+Hf. Example 71 3-r2-f5-ethvl-pvridin-2-vi>-ethoxv'|-phenol To a solution of benzoic acid 3-[2-(5-ethyl-pyridin-2-yl)-ethoxy]-phenyl ester (493 mg, 1.42 mmol, example 70) in 1:1 THF / CH3OH (5 mL) is added ION NaOH soln. (0.5 mL) and water (50 uL). The reaction mixture is stirred for 15 min then cooled to 5°C, adjusted to pH 7 with 2N HCl soln. and diluted with EtO.Ac. The organic layer is washed sequentially with brine, sat NaHCOj soin. then dried over MgS04 and concentrated. The residue is purified by several triturations with hexane to give the title compound as a crystalline solid. MS (ESI) 244 (M-rH)". Example 71a 3-f2-pvridin-2-v!-ethoxv)-phenol The title compound is prepared using essentially the same procedure used in example 71 except using benzoic acid 3-(2-pyridin-2-yl-ethox.y)-phenyI ester (example 70a) in place of 3-[2-(5-ethyI-pyridin-2-yl)-ethoxy]-phenyl ester. MS (ESI) 216 (M+H)*. Example 72 r3-('2-Methoxy-ethoxvmeihoxv)-phenvI1-methanol To a cooled suspension (0°C) of 60% NaH (660 mg, 16.5 mmol) in THF (35 mL) is added dropwise a solution of 3-hydroxyben2aldehyde (1.89 g, 15 mmol) in THF (15 mL)'andthe resulting mixmre stirred for 20 min. To the mixture is added 2-methoxyeihoxymethy] chloride (1.88 mL, 16.5 mmol) and DMPU (5 mL), the cold bath removed and stirred for J hr. The reaction mixture is cooled to 0 °C then slowly added 2M NaBH4 (in trigiyme) (3.75 mL, 7.5 mmol) and let stir for 1 hr. Slowly quenched with 2N HCI soin (3.9 mL) and diluted reaction mixture with ether. The organic layer is washed with brine, dried over MgS04 and concentrated. The residue is purified by flash chromatography (silica, 60% ethyl acetate in hexares) to give the title compound as a pale yellow oil. MS (EI) 212 (M)"^. Example 73 I 2-f3-(2-Methoxy-ethoxvmethoxv)-benzvioxymethyl1-pyridine To a cooled solution (0°C) of [3-(2-methoxy-elhoxymethoxy)-phenyi]'methanol (212 mg, 1 mmol, example 72) in THF (3 mL) is added 60% NaH (80 mg, 2 mmol) and the mixture stirred 10 min. Added 2-picolyl chloride hydrochloride (164 mg. 1 mmol) and DMPU (0.8 mL), removed cold bath and let reaction mixture stir for 2 hrs. Quenched reaction with sat NH4C! soin. and diluted with EtOAc The organic layer is washed with brine, dried over MgS04 and concentrated. The residue is purified by flash chromatography (silica, 70% ethyl acetate in hexanes) to give the title compound as a pale yellow oil. MS (ESI) 304 (M-^H)"". The following compounds are prepared using essentially the same procedure used in exarapie 73 except using the cited halide in place of 2-picoiyl chloride hydrochloride. Example 73 a 2-f3-f2-Methoxy-ethoxvmethoxvVbenzvioxvmethyl1-qmnoline MS (ESI) 354 (M+H)'. Prepared from 2-{chloromethyl)quinoiine hydrochioride. Example 73b 4-Chloro-2-r3-f2-meihoxv-ethoxvmethoxy>benzvloxvmethyll-quinoIiDe MS (ESI) 388 (M+H)". Prepared from 2-chIoromethyI-4-chloroquinaline (example 46). Example 73c 6-Methoxv-2-I3-(2-methoxv-ethoxvTnethoxy>-bgnzvloxYmethvI1-quinoIine MS (ESI) 384 (M+H)*. Prepared from 2-chloromethyl-6-methoxyqmnoiine (example 46b). Example 74 3-fPyridln-2-vlmethoxvmethvI>-phenol To a solution of2-[3-(2-methoxy-ethoxymethoxy)-benzyioxymeihyI]-pyridine (171 mg, 0.56 mmol, example 73) in CH3OH (1.9 mL) is added p-toluenesulfonic acid monohydrate (148 mg, 0.78 mmol). The mixture is heated to 60°C and sthred for 1.5 hrs, then cooled to room temperature and diluted with EtOAc. The organic layer is washed with sat NaHC03, brine, then dried over MgSOj and concentrated to give the title compound as a while crystalline solid. MS (ESI)216(M+H)*. The following compounds are prepared using essentially the same procedure used in example 74 except using the cited MEM ether in place of 2-[3-(2-melhoxy-ethoxymethoxy)-benzyloxymethylj-pyridine. Example 74a 3-fOuinolin-2-vimethoxvm ethyl yphenol MS (ESI) 266 (M+H)*. Prepared from 2-[3-(2-methoxy-ethoxymethoxy)-benzyloxymethy!]- quinoiine (example 73a). Example 74b 3 -(4-Chloro-q uinolin-2-vlmethoxvmethvl)-phenol MS (ESI) 300 (M+H)*. Prepared from 4-chloro-2-[3-(2-methoxy-ethDxymethoxy)- benzyloxymethylj-quinoline (example 73b). Example 74c 3-f6-Methoxv-quinolin-2-vlmeIhoxvinethvi>-phenol MS (ESI) 296 (M+H)*. Prepared from 6-meihoxy-2-[3-(2-meihoxy-ethoxymethoxy)' benzyloxymethylj-quinoline (example 73c)- Example 75 [2-(3-Hvdroxvmethvl-phenoxvmethvl>-6-methvl-phenoxv1-acetonitriie To a solution of 3-hydroxyben2yl alcohol (202 mg, 1.63 mmol) in DMF (5.4 mL) is added KiCOj (247 mg, 1.79 mmol) and (2-bromomethyl-6-methyl-phenoxy)-acetonitrile (430 mg, 1.79 mmol, example 24). Heated resulting mixture to eO^C and stirred for 3 hrs then cooled to room temp and diluted with ether. Washed organic layer with water, brine, dried over MgS04 and concentrated. The residue is purified by flash chromatography (silica, 30% ethyl acetate in hexanes) to give the title compound. MS (£1) 283 (M)*. Example 76 ) [2-f3-BromQmethvl-ohenoxvmethvl)-6-methv!-phenoxv1-acetomtrile To a solution of [2-(3-hydroxymethyl-phenoxymethyl)-6-methyl-phenoxy]-3cetonitrile (230 mg, 0.81 mmol, example 75) in THF (3 mL) is added PhsP (233 mg, 0.89 mmol) and stirred until homogeneous. Cooled solution to 0°C then added portionwise NBS (151 mg, 0.85 mmol) and let stir 45 min. Concentrated reaction mixture under reduced pressure. The residue is purified by flash chromatography (silica, 40% CUiCU in hexanes) to givethe title compound as a white cn'stalline solid. MS (EI) 345, 347 (M)*, Br pattern. Example 77 6-Meihoxv-3-methvl-l,3-dihvdro-indol-2-one To a cooled solution (-7S°C) of 6-methoxy-13-dihydro-indoi-2-one (840 mg, 5.2 mmoU See Quallich, Synthesis 1993, 51-53) in THF (20 mL) is added dropwise TMEDA (1.57 mL, 10.4 mL)foIlowed by dropwise addition of2.5Mn-BuLi (4.16mL, 10.4 mmol). Themixtureis aiiowed to stir for 15 min then warmed to -25°C. lodomethane (405pLL, 6.5 mmol) is added dropwise and stirred for 20 min. The reaction is quenched with sat NH4CI soln, warmed to room temp and diluted with EtOAc. Washed organic layer with sat NH4CI soln, brine, dried over MgS04 and concentrated. The residue is purified by flash chromatography (silica, 45% ethyl acetate in hexanes) to give the title compound. MS (ESI) 178 (M+H)*. Example 78 6-Methoxy-3.3-dimethyl-1.3-dihvdro-indoI-2-one To a cooled solution (-78'C) of 6-methoxy-3-methyl-13-dihydro-indol-2-one (679 mg, 3.83 mmol, example 77) in THF (13 mL) is added TMEDA (1.16 wL, 7.66 mmol) followed by dropwise addition of 2-5M n-BuLi (3.06 mL, 7.66 mmol). The mixture is stirred 15 min then waraied to-25°C. lodomethane (275jiL, 4.40 mmol) is added dropwise and stirred for 30 min. Reaction is quenched with sat NH4CI sohi, warmed to room temp and diluted with EtOAc. Washed organic layer with sat NKiCi soln, brine, dried over MgS04 and concentrated. The residue is purified by flash chromatography (silica, 35% ethyl acetate in hexanes) to give the title compound as a white crystalline solid. MS (ESI) 192 (M+H)*. Example 79 6-Methoxv-l ■3.3-trimethvI-13-dihvdro-indol-2-one To a cooled solution (-5'-0°C) of 6-methoxy-3,3-dimethyl-l,3-dihydro-indoI-2-one (600 mg, 3-14 mmol, example 78) in THF (10.5 mL) is added 60% NaH (132 mg, 3.30 mmol) and is stirred for 15 min. lodomethane (215 ^L, 3.45 mmol) is added to the reaction mixture and stirred for 2 hrs. Quenched reaction with sal NH4C] soln and diluted with EtOAc. Washed organic laver with sal HH4CI soin, brine, dried over MgSOa and concentrated. The residtie is purified fav flash chromatography (silica, 30% ethyl acetate in hexanes) to give the titie compound as a white crystalline solid. MS (ESI) 206 Example 80 6-Hvdroxv-l .jj-trimethyl-l .3-dihvdro-indol-2-one To a solution of 6-methoxy-U33-trimethyH,3-dihydro-indol-2-one (601 mg, 2.93 mmol, ) example 79) in acetic acid (880 ^L) is added hydrobromic acid (48% in H2O) (8.8 mL). The resulting solution is heated to reflux (105*-110**C), stirred 2 hrs, then cooled to room temp and concentrated under reduced pressm-e. The residue is dissolved in EtOAc and the organic layer washed with water, brine, dried over MgS04 and concentrated. The residue is pioified by triturating with a small volume of ether to give the title compound as an off white solid. MS (ESI) 192 (M+H)*. Example 81 2-r3-f2-Methoxy-ethoxvmethoxy)-benzvloxy1-qtiinoline To a suspension of 60% NaH (44 mg, 1.1 mmol) in DMSO (2 mL) is added dropwise a solution of [3-(2-methoxy-ethoxymethoxy)-phenyl]-methanol (212 mg, 1.0 mmol, example 72) in DMSO (1 mL). Let stir 20 min. then added 2-chloroquinoline (180 mg, 1.1 mmol) and heated to 100 "C for 1 hr. Cooled reaction mixture to room temp, and diluted with EtOAc. The organic layer is washed with sat. NH4CI sohi., brine, dried over MgS04 and concentrated. The residue is purified by flash chromatography (silica, 25% ethyl acetate in hexanes) to give the title compotmd as a colorless oil. MS (ESI) 340 (M+H)*. Example 82 isoburvi2-T3-(methoxvVDhenvlsulfanvlmethvn-6-methvl-benzoate A IQN solution of sodium hydroxide (0.32 mL, 3.2 mmol) is added slowly to a solution of 5-methoxybenzenethiol (0.42 g, 3.0 mmol) in isobutanol (2 mL) followed by a solution of isobutyl 2-bromomeihyl-6-methy!-benzoate (0.96 g, 3.3 mmol, example 2) in isobutanol (2 mL). The reaction is allowed lo slir 15 min and is then panitioned between ethyl acetate and dilute aqueous HCl. The organic phase is washed with water, dried over magnesium sulfate, concentrated and purified by column chromatography (silica, 40% dichloromethane in hexanes) to provide the title compound. MS (EI) 344 (Mf. - Example 83 Isobutyl 2-r3-(hvdroxy)-phenvl5ulfanvlmeihyn-6-methvl-ben2oate Boron tribromide (1.3 mL, 1.0 M in dichloromethane, 1.3 mmol) is added to a solution of isobutyl 2-[3-(methoxy)-phenyIsulfanyIinethyI3-6-methyI-benzDate (194 mg, 0.56 mmol, example 82) in dichloromethane (3 mL) at 0 "C and then the reaction is stirred at room temperature 3h. The reaction is then partitioned between sodium bicarbonate solution and ethyl acetate. The organic phase is dried over magnesium sulfate, concentrated and purlSed by column chromatography (silica, 15 % ethyl acetate in hexanes) to provide the titie compound. MS (EI) 330 (M)^ Example 84 Isobutyl 2-methvl-6-f3-fquinQlin-2-vlmethoxv)-phenYlsulfanvimethvn-benzoate The free base of 2-(chloromethyl)quinoiine hydrochloride (148 mg, 0.69 mmol) is prepard by partioning the material between ethyl ether and sodium bicarbonate and drying the organic phase with inagnesium sulfate. This material is then dissolved with isobutyl 2-[3-(hydroxy)-phenyIsuifanylmethy]]-6-metbyl-benzoate (220 mg, 0.67 mmol, example 83) in DMF (2 mL) at 0 °C and sodium hydride (60%, 27 mg 0.67 mmol) is added. The reaction is allowed to stir 16 h and is then partitioned between ethyl acetate and water. The organic phase is washed with water (3X), dried over magnesium sulfate, concentrated and purified by column chromatography (silica, 10% ethyl acetate in hexanes) to provide the title compound. ^H NMR (300 MHz, CDCb) 5 8.19 (d. IH), 8.08 (d, IH), 7.83 (d, IH), 7.74 (t, IH), 7.63 (d, IH), 7.55 (t, IH), 7.18-7.07 (m, 4H), 6.99 (d, IH), 6.89 (d, IH), 6.82 (dd, IH). 5.33 (s, 2H), 4.18 (s, 2H), 4.10 (d, 2H), 2.36 (s, 3H), 2.07-2.01 (m, IH), 0.98 (d, 6H); MS (ESI) 472 (M+Uf. Example 85 Isobutvl2-methv{-6-r3-(quinolm-2-vlmethoxvVphenvlsuIfmvIinethvn-benzoate m-Ch)oroperbenzoic acid { Example 86 Isobutvl 2-methvl'6-r3-(quinolm-2-vtmethoxv>-phenylsulfonvlmethvn-beii2oate m-Cfaloroperbenzoic acid ( Example 87 fl-OuinoIin-2-vlmetbvl-lH-imidazol-4'Vl)-mgthanolandf3-quinolin-2-vhnethvl-3H-inudazoM-vD-methanol 2-ChloromethyI-quinoiine hydrochloride (2.24 g, 10.5 mmol). 4-(hydroxymethyl)-imidazoie hydrochloride (1.35 g, 10 mmol) and K2CO3 (4.2 g, 30 mmol) are dissolved/suspended in anhyd. DMF (20 mL) and heated to 100 °C with rapid stirring overnight. The reaction is cooled to r.t. and poured into water (400 mL) and extracted with chloroforin (3 x 150 mL). The organic fractions are pooled and washed with brine (2 x 200 mL), dried over MgS04, filtered and reduced under vacuum to an oil. The crude materia! is purified by flash chromatography (silica, 5% methanol in dichloromethane) to give (3-qmnoiin-2-ylmethyl-3H-imidazol-4-yl)-methanol and (l-quinoIiD-2-yimethyi-IH-imidazoI^-y])-methanoi in a 2:3 ratio. The idemit\- of each regioisomer was deiermined by NMR NOE experiments. MS (ESI) 240 (M+H)* found for both regioisomers. Example 88 isobutyl 2-methvi-6-('l-qmnolin-2-v]methvl-lH-imidazol-4-vimethoxymethvlVbenzoate (l-QmnoUn-2-ylmethyI-lH-imidazol-4-yl)-methanol (350 mg, 1.46 mmol, example 87) is dissolved in 20% DMPU in THF (5 mL) and cooled to 0 "C. Sodium hydride (60%, 60 mg, 1.50 mmol) is added portionwise, and the contents stirred for 15 min. Isobutyl 2-bromomethyI-6-methyl-benzoate (57%, 730 rag, 1.46 mmol, example 2) is added, the reaction is allowed to come to r.t and stiired overnight The contents are poured into water (200 mL) and extracted with dichloromethane (3 x 75 mL). The organic fractions are pooled and washed with brine (3 x 100 mL), dried over MgS04, filtered and reduced under vacuum to an oil. The crude material is purified by flash chromatography (silica, 3% methanol in dichloromethane) to give the title compound. MS (ESI) 443 (M+H)*. Example 88a Isobutyl 2-methvl-6-f3-quinolin-2-vlmethvI-3H-imidazol-4-vlmethoxvmethvl)-ben2Date The title compound is prepared using essentially the same procedure used in example 88 except using (3-quinolin-2-ylmethyl-3H-imidazoi-4-yi)-methanoI in place of (l-quinolin-2-yimethyl-l H-imidazoi^yI)-methanol. MS (ESI) 443 (M+Kf. Example 89 2-Methvl-6-fl-quinolin-2-vlmethvl-lH-imidazol-4-vlmethoxvmethvI)-benzoic acid Isobutyl 2-methy!-6-(l-quinolin-2-ylmelhyI-lH-imidazol-4-ylmethoxymethyI)-benzoate (300 mg, 0.68 mmol, example 88) is dissolved in ethanol (5 mL). 10 N NaOH (680 ^L, 6.8 mmol) is added and the contents heated to 90 °C overnight. The reaction is cooled to r.t., 2 N HCl (3.4 mL, 6.8 mmol) is added and the pH adjusted to- 5-7. The contents are poured into water (100 mL) and extracted with chloroform (3 x 75 mL). The oi^anic fractions are pooled, washed with brine (3 x 100 mL). dried over MgS04. filtered and reduced under vacuum to an oil. The crude material is purified by HPLC (C-! 8. 25-50% aceionilrile in water over 15 min.) to give the title compound as the TFA salt. 'H NMR (300 MHz. CDCI3) 5 8.93 (s, ]H), g.31 (d, IH), 8.07 (d, IH), 7.86 (d, IH), 7.78 (t, IH), 7.63 (t, IH), 7.51 (d, IH). 7.44 (s, IH), 7.17-7.12 (m, IH), 7.06-7.01 (m. 2H), 5.64 {s, 2H), 4.66 (s. 2H), 4,48 (s, 2H), 2.29 (s, 3H). MS (ESI) 388 (M+H)*. i Example 89a 2-MethvI-6-f3-quinoIin-2-vlmethvl-3H-imida2ol-4-vlme^oxvmethvi')-benzoicacid The title compound is prepared using esseniially the same procedure used in example 89 except using isobutyl 2-methyl-6-(3-quinolin-2-yImethyl-3H-iniidazol-4-ylmethoxyinethyi)-benzoate in place of isobutyl 2-methyl-6-{ 1 -quinoIin-2-ylmethyl- lH-imidazol-4-yImethoxyniethyI)-ben2Date. 'H NMR (300 MHz, CDCb) 5 8.95 (s, IH), 8.27 (d, IH), g.OS (d, IH), 7.82-7.76 (m, 2H), 7.64-7.59 (m, IH), 7.46 (s, IH), 7.38 (d, IH), 7.10-6.99 (m, 2H), 6.92 (d, IH), 5.91 (s, 2H), 4.52 (s, 2H), 4.49 (s, 2H), 223 (s, 3H). MS (ESI) 388 (M+H)* Example 90 2-r3-fIH-Indoi-3-vlmethvl>-pbenoxvmethvl"|-quinoline Indole (230 mg, 2.0 mmol) is dissolved in tetrahydrofiiran (3 mL) and ethyim^nesium bromide (I M, 2.0 mL, 2.0 mmol) is added and the reaction is heated for 2 h at 65 °C. The free base of 2-(3-chloromethyl-phenoxymethyI)-quinoiine hydrochloride (400 mg, 1.2 mmol, example 49) is prepard by partioning the material between ethyl ether and sodium bicarbonate and drying the organic phase with magnesium sulfate. This free base is dissolved in tetrahydrofiiran (2 mL) and is added to the cooled indoIe/Grignard solution, along with catalytic tetrabutylammonitim iodide. This mixrure is heated 6 h at 65 °C. The reaction is then cooled and partitioned between ethyl ether and ammonium chloride. The organic phase is washed with brine, dried over magnesium sulfate, concentrated and purified by column chromatography (silica, dichloromethane) to yield the title compound. MS (ESI) 365 (M+H)^ Example 91 f3-r3-fauinDlin-2-vlmethoxv)-benzvil-indol-l-vU-aceticacid Sodium hydride (60%, 22 mg, 0.55 mmol) is added to a soiulion of 2-[5-(lH-indol-3-ylTneihyI)- phenoxymethyl]-quinoIine f90 mg. 0.25 mmol. example 90) in DMF (2.5 mL). After stirring 5 minutes ethyl bromoaceiate (0.1 mL, 0.9 mmol) is added and the reaction is allowed to stir 2h. The reaction is partitioned between ethyl acetate and amraoniiim chloride and the orsanic phase is washed with water. The organic phase is dried over magnesium sulfate, concennated and then the solid is tiiurated with ethyl-ether and ethyl acetate to provide the title compound as a solid. m.p. 151-159 "C; 'H NMR (300 MHz, CDCI3) 5 8.20 (t, 2H), 7.S3-7.80 (m, IH), 7.77-7.71 (m, IH), 7.67 (d, IH), 7.61-7.53 (m, IH), 7.45-7.42 (m, IH), 7.29-7.14 (m, 3H), 7.05-6.99 (m, 2H). 6.94 (s, IH), 6.85 (m, 2H), 5.16 (s. 2H), 4.84(s, 2H), 4.11 (s, 2H); MS (ESI) 423 CM+H)^ Example 92 Ethyl f2-fonnvl-6-methvl-2-phenoxy>-acetate Ethyl bromoacetate (4.5 mL, 40 mmol), 2-hydroxy-3-methyI-ben2aldehyde (5 g, 37 mmol and potassium carbonate (8.1 g, 59 mmol) are combined in acetone (60 mL) and refluxed overnight The reaction is filtered and the solvent removed from the filtrate imder reduced pressure to give the title compound. MS (GC-MS) 222 (M)*. Example 93 Ethyl 7-melhvl-benzofiiran-2-carboxyIate Sodium (0.52 g, 23 mmol) is dissolved in ethanol (60 mL) and to this is added ethyl (2-formyl-6-methyI-2-phenoxy)-acetate (5 g, 23 mmol, example 92). This mixture is refluxed for 3 hours and the solvent is removed in vacuo. The residue is dissolved in dichiorometfaane/watei and acidified with IN HCl. The organic layer is washed with water and brine and then dried over magnesium sulfete and the solvent removed in vacuo. The residue is purified by flash chromatography (silica, 1% methanol in dichloromethane) to give the title compound. MS (GC-EI) 176 {M>+. Example 94 Ethvl 7-bromomethvi-benzofuran-2-carboxvlate Ethyl 7-methy]-ben2ofuran-2-carboxylate (0.5 g, 2.4 mmol, example 93), N-bromosuccinimde (0.48 g, 2.7 mmol) and benzoyl peroxide (0.06 g, 2.4 mmol) are combined in carbon tetrachloride (10 mL) and heated in an oil bath at 90°C overnight. The reaction is filtered and the filtrate solvent is removed in vacuo. The residue is purified by flash chromatography (silica, 5% to 10% ethyl acetate in hexanes) to give the title compound. MS (GC-EI) 360, 362 (NT, Br partem). Example 95 Ethyl 2-meihvl-6-trifIuoromethanesu]fonv]oxv benzoate Ethyl 6-methylsalicy!ate (2.5 g, 14 mmo!. See, Hauser, Frank M., Synthesis 1980, JO, 814-15) is dissolved in THF (20 mL) under nitrogen and cooied in an ice bath. Sodium hydride (60%, 0.56 g, 14 mmol) is added and the mixture is stirred 15 minutes. Then DMPU (0.20 mL) and N-phenyl-trifluoromethanesulfonimde (5.0 g, 14 mmol) are added and the reaction is stirred with cooling for 2 hours. Tlie solvent is removed in vacuo and ether is added and the organics are washed with water, then dried over magnesium sulfate and concentrated under reduced pressure. The residue is purified by flash chromatography (silica, dichloromethane) to give the title compound. Example 96 3-(2-methoxv-ethoxvmethoxv)-phenvliodide To a suspetKion of 60% sodium hydride (1.76 g, 44 mmol) in THF (10 mL), cooled to CC, is added 3-iodophenol (8.8 g, 40 mmoi) and methoxyethoxymethyl chloride (5 mL, 44 mmol) in THF(50mL). Then DMPU (10 mL) is added, the cooling bath is removed and the reaction is stirred for an hour. The reaction is diluted with ether, washed with water and brine and the organic layer dried over magnesium sulfate. The solvent is removed in vacuo to give the title compound. Example 97 F3-l'2-MethQXv-eihoxvmethoxv)-phenvlethvnvn-trimethvl silane 3-f2-Methoxy-ethoxymethoxy)-phenyliodide (12.1 g, 39 mmol, 96) and tetrakis(triphenylphosphine)panadium (1.2 g, 1.0 mmol) and cuprous iodide (0.095 g, 0.5 mmol) are dissolved in THF (120 mL) and to this is added piperidine (12 mL) and (trimethyisilyl)aceiyiene (8 mL, 57 mmol). This mixture is degassed and is then stirred for 2 hours. The reaction is then diluted with ether and washed rwice with water and brine and the organic layer dried over magnesium sulfate. The solvent is removed in vacuo lo give the title compound. MS (EI) 206 (M)"". Example 98 Ethyl-2-r3-('2-methoxv-ethoxvmethQxv)-phenvlethvnvi]-6-methvl-benzQate [3-{2-Methoxy-ethoxymethoxy)-phenyIethynyl]-trimethyl silane (0.57 g, 2 mmol, example 97) and 1.0 M tetrabutytammonium fluoride (2.1 mL, 2 mmol) are added to IHF (10 mL) and acetic acid (0.13 g, 2 mmol) is added and this mixture is stirred at lO^C, under nitrogen. After 15 minutes, the solvent is removed in vacuo and the residue is azeotroped with benzene and purified by flash chromatography (silica, 20% ethyl acetate, 30% dichloromethane in hexanes) to give I-ethynyI-3-(2-methoxy-ethoxymethoxy)-beiizene (0.28 g, 1.4 mmol) which is dissolved in THF (8 mL), cooled to -78°C, under nitrogen and to this solution is added 2.5M n-buty! lithium (0.56 mL, 1.4 mmol) dropwise over 30 seconds. After stirring for 15 minutes, 1 .OM zitic chloride in ether (1.4 mL, 1,4 mmol) is added dropwise over 30 seconds and this mixture is stirred for 30 minutes. Bis-(dibenzylideneacetone) palladium (0 04 g, 0.07 mmol) and bis (diphenyl phosphino) ferrocene (0.04 g, 0.07 mmol) is added and to this mixture is added ethyI-2-methyl-6-trifluQrQmethanesulfQnyloxy benzoale (0.44 g, 1.4 mmol, 95) iaTHF (2 mL). The cooling balh is removed and the reaction allowed to warm to room temperature. Then the reaction mixture is heated in an oil bath at 65°C overnight. The reaction is then diluted with ethyl acetate (50 mL), washed with saturated ammonium chloride and brine and then dried over magnesium sulfate. The solvent is removed in vacuo and the residue purified by flash chromatography (silica, 10% ethyl acetate, 25% dichloromethane in hexanes) to give the title compound. MS (ESI) 369 {M+Hf. Example 99 l'3-MethvI-4-oxo-3.4-dihvdro-QuinazoIin-2-vlVmelhvI chloride. To a suspension of isaioic anhydride (1.63g, lOmmoOin dioxane (40mL) is added raethylamine solution (5 mL, 2M in THF). The resulting solution is stirred for Ih then concentrated under vacuum. The residue is taken up in toluene (30 mL) then pyridine (5.5 mL) is added followed by a solution of chloroacetyl chloride (2.7 mL- 34 mmo!) in toluene (15 mL). The resulting mixture is siirred for 15 h. The solid product is filtered, washed with water, then dried under vacuum to give 2.1g of a tan solid. A portion of this product (452 mg, 2 mmol) is suspended in benzene (10 mL) then p-toluene sulphonic acid monohydrate (3 94 mg, 2 mmol) is added. This mixture is warmed Jo 70 °C and stirred at this temperature for 10 h. The mixiure'is then cooled to room temperature and the benzene solution decanted. The residual solid is mixed with sodium bicarbonate solution (saL) and this mixture is extracted with ethyl acetate / methanol / dichloromethane. The combined exffacts are washed with brine, dried over MgS04 and concentrated to give the title compound as a tan solid. 'H NMR (300 MHz, CDCI3): 5 8.28 (d, IH), 7.75 (t, IH), 7.67 (d, IH), 7-5! (t, IH), 4.62 (s, 3H), 3.76 (s, 3H). Example 100 3-(2-Hvdroxvmethyl-3-methvl-benzvloxvVphenol To a cooled (0 °C) soltition of methyl 2-methyl-6-[(3-hydroxy-phenoxy)-methyI}-ben2oate (220 mg, 0.76 mmol, example 5) in THF (2 mL) is added lithium aluminum hydride solution (1.5 mL, 1M in THF). The resulting solution is stirred for 10 min then warmed to room temperature, and stirred for 40 min. This solution is then cooled to 0 "C and water (75 mL) added, dropwise, followed by sodium hydroxide solution (75 mL, 5N) and water (75 mL). The resulting suspension is diluted with ether, filtered through celite and the solid washed thoroughly with methanol (until the solid is free of product by TLC analysis). The combined filtrates are concentrated under vacuum to give the title compound as a w^te solid- MS (EI) 244 (Mf. Example 101 2-r3-(2-Hvdroxymethyl-3-methvl-benzvloxv)-phenoxvmethvn-3-methvl-3H-quiDazolin-4-one To a solution of 3-(2-hydroxymethyl-3-methyi-benzyloxy)-phenol (87 mg, 0.38 mmol, example 100) and (3-methyl-4-oxo-3,4-dihydro-quinazolin-2-yl)-methyl chloride (94 mg, 0.45 mmol, example 99) in DMF (1 mL) is added powdered K2CO3 (78 mg, 0.5 mmol). The resulting mbcture is warmed to 60 °C and stiired at this temperature for 5h. This mixture is cooled to room temperature, diluted with ethyl acetate, washed with water and brine, dried over MgS04 and concentrated. The residue is purified by flash chromatography (silica, 40% ethyl acetate / 30% dichloromethane in hexanes ) to give the title compound as a foam. MS (ESI) 417 (M+H)'. Example 101a {2-l"3-('5-CvclofauTvl-n.2.41oxadiazol-3-vImethoxv)-phenoxvmethv]l-6-methvI-DhenvU-methanol The title compound is prepared using essentially the same procedure used in example 101 except using 3-chloromethyI-5-cyclobutyl-[l,2,4)oxadia2ole in place of (3-methyI-4-oxo-3,4-dihydro- quinazoiin-2-yI)-methyl chloride. MS (ESI) 381 (M+H)^ Example 102 2-Methvl-6-f3-f3-methyl-4-oxo-3.4-dihydro-quiDazoiin-2-yUnethoxy)-phenoxvmethvl]-benzaldehyde To a cooled (-78 °C) solution of oxalyl chloride (2.5 mL, 1.75 M in CH2CI2) is added, dropwise, DMSO ( 80 mL). On complete addition, a solution of 2-[3-(2-hydroxymethyI-3-methyl-benzyloxy)-phenoxymethyI]-3-methyl-3H-quina2olin-4-one (120 mg, 0.28 nunol, example 101) in dichloromethane (1 mL) is added dropwise. TMs solution is stirred for 5 min then triethylamine (276 mL, 2mmoI) is added in one portion. The cold bath is removed and stirrii^ continued for 10 min. The mixture is then diluted with ethyl acetate, washed with water and brine, dried over MgS04 and concentrated to give the title compound as a solid. MS (ESI) 415 (M+H)"". Example 102a 2-f3-f5-CyclobutyI-ri^.4"|oxadiazol-3-ylmethoxv>-phenoxvmeIhvl1-6-methvI-bemaIdefayde The title compound is prepared using essentially the same procedure used in example 102 except using {2-[3-(5-cycIobutyI-[l,2,4]oxadia2ol-3-yimethoxy)-phenoxymethyI]-6-methyI-phenyl}-methanol (example 101a) in place of 2-[3-(2-hydroxymethyl-3-methyl-benzyIoxy)-phenoxymethyI]-3-mcthyi-3H-quina2olin-4-one. MS (ESI) 379 (M+H)". Example 103 2-Melfavl-6-r3-r3-methvl-4-oxo-3.4-dihvdro-auinazolin-2-vlmethoxv)-phenoxvroethvl1-benzoic To a suspension of 2-meihyl-6-[3-(3-methyl-4-oxo-3,4-dihydro-quinazoiin-2-yimeihoxy)-phenoxyineihyI]-benzaldehyde (120 mg, 0.28 mmol, example 102) in r-butanol (1.5 mL) is added iso-butene (0.5 mL) followed by NaClOT (220 mg, tech.grade 1.6 mmol) in water (1.5 mL) and NaH2P04-H20 (220 mg, 1.6 mmol) in water (1.5 mL). This mixture is stirred for Ih (during which time the solids dissolve) then diluted with ethyl acetate, washed with water and brine, dried over MgS04 and concentrated. The residue is purified by flash chromatography (10% methanol in dichloromethane). This product was suspended in chloroform and filtered through celite. The filtrate is concentrated under reduced pressure to give the title compound as an amorphous solid. 'H NMR (300 MHz, CDCI3): 5 8.41 (d, IH), 7.84 (m, 2H), 7.62 (m, IH), 7.33 (m, 2H), 7.20 (m, IH), 7.14 (t, IH), 6.81 (m, IH), 6.70 (m, 2H), 5.29 (s, 2H), 5.25 (s, 2H), 3.80 (s, 2H), 2.52 (s, 3H). MS (ESI) 430 (M+H)^ Example 103a 2-r3'(5-Cyclobutvl-fl^.41oxadiazol-3-vimethoxy')-phenoxvmethvn-6-methvl-benzoicacid The title compotmd is prepared using essentially the same procedure used in example 103 except using 2-[3-(5-Cyclobutyl-[l,2,4]oxadiazol-3-yimethoxy)-phenoxymethyl]-6-methyI-benzaldehyde (example 102a) in place of 2-methyl-6-[3-{3-methyI-4-oxo-3,4-dihydro-quina2Dlin-2-ylmethoxy)-phenoxymethyIJ-ben2aldehyde. 'H NMR (300MHz, DMSO) 5 7.10 (m, 4H), 6.68 (s, IH), 6.60 (m, 2H), 5.19 (s. 2H), 5.13 (s, 2H), 3.86 (m, IH), 2.36 (m, 4H), 2.28 (s, 3H), 2.08 (m, IH), 1.96 (m, IH). MS (ESI) 395 (M+H)". Example 104 5-Phenvl-2-methvlpyridine To a cooled (-TCC) solution of 3-phenylpyridiiie (L43 mL, IQ.Q mmoles) in diethyl ether (7.5 mL) is added dropwise methyllitluum (LiBr complex, 1.5 M in diethyl ether, 7.33 mL, 11.0 mmoies). After letting warm to room temperature over 16 hours the reaction is cooled (0°C) and quenched with distilled water (5 mL). The reaction is then extracted with methylene chloride, the organic layer isolated and concentrated, and the resulting residue purified by column chromatography (silica, 3: i hexane: EtOAc) to yield the title compound as a pale yeilow oil. MS(ESI)170(M+H)'. Synthesis of a compound of Formula fVl) A compound of FomiuJa (VI) is prepared in a multi-siep synthesis lilustraied in the below scheme. The key starting materia! is quinaldine. In the first stage it is chiorinated lo form 2-chioromethylquincline which, without isolation, is reacted with hydroquinone to form the intermediate 4-(quino!in-2-y[-methoxy)phenoI (VIII). This intermediate is then treated with a,a'-dichloro-o-xylere to form 2-[4-quinolin-2-yl-methoxy)phenoxymethy!]benzyi chioride, which is convened in siiu to 2-[4-quinDlin-2-yl-methoxy)phenoxyinethyl]pheny[acetonitrile (IX), the penultimate precursor to (VI). (IX) is converted to (VI) crude, in a reaction with sodium azide and ammonium chloride which transforms the nitriie group into the tetrazole ring. The purification of the final product is accomplished by recrystallization of the crude material from methanol to afford pure (VI). A IL round bottom flask is charged with 4~(bromoniethy])benzQic acid (32JJ6 g, 150.0 mmole) a:id dichloromethane (650 mL). A stir bar is carefully added and the reaction flask is immersed in an ice-water bath. After approximately 15 minutes, oxallyl chloride (15.7 mL, 180 moles) is added. After approximately 15 minutes, N,N-dimethylfonnaide (500 mL, cat) is added. The reaction began to bubble. After stirring for 1.5 hours, the ice-water bath is removed. After stirring for 3 hours at ambient temperature, the effervescence has ceased. At the end of this period, the slirbar is removed from the reaction mixture and the reaction solvent is removed in vacuo. After the solvent has been removed, more dichloromethane is added to the reaction flask and this too is removed in vacuo. A three neck 3L round bottom flask is charged with dry N,N-dimethylfarmamide (13 L), N,N-diisopropylethylamine (39.19 mL, 225 mmoles), 4-N,NHd(methylaminopyridine (3.67 g, 30 mmole) and MicroKANS [1456, 15 mg of Wang resin (1.7 mmole/g loading) per MicroKANs, 25.5 micromoies/microKAN, 37.1 mmoles]. The flask is fitted with an overficad stirring apparatus. After stirring for approximately 15 minutes, a solution of the acid chloride as prepared above in dry N,N-dimethylformamide (200 mL) is transferred into the reaction flask. After 14 hours, the reaction solvent is removed. DMF(i.5 L) is added to the reaction flask. The flask was allowed to stir for approximately 15 minutes and the solvent is drained. The MicroKANs are washed, stirred for 20 minutes and drained in the following sequence repeatedly: DMF (2x6 L), THF (3x6 L), dichloromethane (3 x 6 L) and ether (2 x 6 L). After the final washing the MicroKANs are dried by blowing a stream of nitrogen through the flask with intermittent agitation. After sufficient drying, the MicroKANs are sorted for the next reaction. 2. Phenol Displacement: 20.79 g, no mmoies). The reaction fiask is fined with an overhead stirrer. After 2 hours, sodium cyanoborohydride(2I.37 g, 340 mmoies) is added. After approximately 10 minutes, acetic acid (17.0 mL, 297 mmoies) is added. After stirring for an additional hour, the reaction flask is drained. Me^anol (800 mL) is added to the flask. After stirring for approximately ] 0 minutes, the flask is drained, the-reaction flask is washed repeatedly in the following sequence: DMF (3x4 L), dichloromcthane (1 x 4 L) then methanol (I x4 L), dichloromcthane (i x 4 L) then methanol (I x 4 L), dichloromethane(l x 4 L) then methanol (1 x 4 L), dichloromethane (1 x 4 L) and ether ( 1 x 4 L). After the final washing the microKANS are dried by blowing a stream of nitrogen through the flask with intermittent agitation. After sufficient drying, the MicroKANs are sorted for the next reaction. A three n«;k 2 L round bottom flask is charged with the MicroKANs [784, 15 mgof resin (1.7 mmole/g loading) per MicroKAN, 25.5 micromoIes/microKAN, 20.0 mmoies], and dichloromethane (800 mL). The reaction flask is fitted with an overhead stirrer. N,N-diisopr:pyiethyIaniine (20.9 mL, 120 mmoies) and 4-N,N-dimethylaminopyridine (195 mg, 1.6 ramoles) are added. After approximately 15 minutes, the cyclopentanecarbonyl chloride (10.6 g, 80.0 mmoies) Is added. The reaction was allowed to stir for 61 hours, the reaction flask is drained. Dichloromethane (800 mL) is added to the reaction flask. After stirring for approximately \ 0 minutes, the fiask is drained. This is repeated. The MicroKANs ftom all of the acyiation reactions are randomly combined into two separate large flasks and washed repeatedly in the following sequence: dichloromethane (1 x 4 L), THF (2x4 L), dichloromethane (1x4 L) then methanol (1x4 L), dichloromethane (1 x 4 L) then methanol (1x4 L), dichloromethane (1 x 4 L) then methanol (1 x4 L), dichloromethane (1 x4 L) and ether ( I x4 L). 5. Cleavage: The MicroKAN is sorted into individual weils of IRORI AccuCleave 96 cleavage station. The weil is charged with dichloromethane (6O0 mL) and then with a TFA: dichloromethane mixmre(l:l, 600 mL). After agitating for approximately forty minutes, the reaction welt is drained into 2 mL microtube in an ?6-well format. The reaction well is again chargeid with dichloromethane (600 mL). After manual aeiiaiion, this too is drained into the 2 mL microtube in an 96-weli format. The cleavaae cocktail is A three neck 3L round bottom flask is charged wiih 3-chloro»4-hydroxybenzaldehyde (21.9 g, 140 mmoles) and DMF (1.5 L). The reaction flask is fined with an overhead stirrer and immersed in an ice-water bath. After approximately 15 minutes sodium hydride (60 % dispersion in oil, 6.48 g, 180 mmoles) is carefully added. AfteT approximately 30 minutes, the ice-water bath is removed and the reaction allowed to stir at ambient temperature for I hour. At the end of this lime, theMicroKANs [1274, 25.5 micromoles/microlCAN, 32.5 mmoles] and potassium iodide (1.0 g) are added to the reaction mixture. The reaction flask is immersed into an oil bath which is heated to 60'C. After 14 hours, the reaction flask is removed from the oilbath and allowed to cool to ambient temperature. The reaction solvent is removed. DMF (1,2 L) is added to the reaction flask. The flask is allowed to stir for approximately 15 minutes and the solvent is drained. DMF : water (1:1, 1.2 L) is added to the reaction flask. The flask is allowed to stir for approximately 15 minutes and the solvent is drained- This sequence is repeated at least three times or.until the effluent from the washing is clear, the reaction flasks are washed repeatedly in the following sequence: THF (2 x 4 L), dichloromethane (I x4 L) then methanol (1 x4 L), dichloromethane (1 x4 L) then methanol(] x 4 L), dichloromethane (I x4L)thefi methanoI(l x 4 L), dichloromethane (1 x 4 L) and ether ( 1 x 4 L). After the final washing the MicroKANs are dried by blowing a stream of nitrogen through the flask with intermittent agitation. After sufficient drying, the MicroKANs are sorted for the next reaction. 3. Reductive Amination: A three neck 2 L round bottom flask is charged with the MicroKANs [784, 25.5 micromoies/microK-AN, 20.0 mmoles], irimethylonhoformate (850 mL) and 2-(2-aminoethyl)pyridine removed in vacuo using a Savant Speedvac. The concenlraied products from the cleavage mother piatss are reconstituted with THF and transferred into two daughter plates utilizing a Packard MultiProbe liouid handier. The daughter plates are concentrated in vacuo utilizing a GenieVac. Analytica]: MS: m/z 493 (M'). The methods described above are used to prepare the following compounds of this invention. 5-[2-(4-{2-quinolinylmethoxy)phenoxymethy!)benzyl]tetrazole (M.P. 108-11 I'C) CALC: C, 59.87; H, 5.96; N, 13.96 FOUND: C, 59.67, 60.01; H, 5.62, 5.63; N,. 13,73, 13.77 5-[4-Methoxy-3-(3-{2-quino[inylmelhoxy)phenoxymethyl)phenyl]tetr22ole (M.P. 184-87°C) CALC: C, 67.63; H, 4.88; N, 15.78 FOUND: C,67.18;H,5.!3;N, 15.40 5-[3-(4-(2-quinonnyimethyloxy)phenoxymethyl)phenyI]tetrazolefM.P. 176-I77°C) CALC: C, 69.63; H, 4.75; N, 16.92 FOUND: C, 69.58, 69.64; H, 5.00. 4.98; N, 16.66, 16.63 5-[3-Methoxy-4-{4-(2-quinoiinyImethyloxy)bcn2yioxy)pheny!]tetra2ole(M.P. 195-97'C) CALC: C. 67.63; H, 4.88; N, 15.77 FOUND: C, 67.27; H, 4.89; N, 15.41 S-[4-(3-(2-quinolmyimethyloxy)phenoxymethy[)-3methoxyphenyl]tetrazo!e (M.P. 189-91°C) CALC; C, 66.95; H, 4.95; N. 15-61 FOUND: C, 66.48; H, 5.14; N, 14.93 5-[3-(4-(2-quinolinylmethyioxy)phenoxymethy!)benzyl3tetrazole(M.P. I39-44'C) CALC: C, 70.53; H, 5.03; N, 16.45 FOUND: C, 70.33, 70.54; H, 5.25, 5.36; N, 16.38, 16.41 5-[4-(4-(2-quinolinylmethyloxy)phenoxymethyl)benzyI]tetrazole(M.P. 167-71 °C) CALC; C, 67.33; H, 5.31; N, 15.70 FOUND: C, 67.54, 67.67,; H, 5.33, 5.33; N, 15.48, 15.52 5-[4-MeihDxy-3-{4-(2-quinoHnylmelhvloxy)phenylmethvlDxv^nheTivUtetr32D\efM.P_210-i:^°C^ CALC: C. 68.33; H, 4.S2: N. 4.90 FOUND: C, 6S.32; H. 4.90; N, 14.79 4-[3-(2-QumolinyImethy[oxy)phenoxyrnethyl]phenoxyaceTicacid (M.P. I64(dec)) CALC: C, 69.27; H. 5.35; N, 3.23 FOUND: C, 69.53, 69.65; H, 5.11, 5.05; N, 3.21, 3.12 5-[2-(4-(2-QuinoiinylmEthyloxy)phenoxymethyl)phenoxyinethyl]tetrazofe (M.P, 1 SS-SS^C) CALC: C. 65.63; H, 5.08; N, 15.31 FOUND: 0,65.77, 65.52; H, 4.99, 5.03; N, 14.92, 15.03 4-[4-(2-Quinolinylmethyioxy)phenoxymethyl]phenoxyacetic acid (176°C(dec)> CALC: C, 71.50; H, 5.16; N, 3.34 FOUND: C, 71.10, 71.17; H, 5.27, 5.33; N, 3.37, 3.34 4-[3-{2-Quinolinyiniethyloxy)phenoxyinethyl]phenylacetic acid (M.P. 15S-60°C) CALC: C, 75.17; H, 5.30; N, 3.51 FOUND: C, 74.89; H, 5.36; N, 3.37 2-[3-(3-(2-QuinoiinylmethyIoxy)phenoxymethyI)phenoxy]penianoic acid (M.P. 133-35'C) CALC: C, 73.51; H, 5.95; N, 3.06 FOUND: C, 73.35, 73.60; H, 5.95, 5.98; N, 3.08,3.05 2-[3-{2-Quinoimyimelhyloxy)phenoxyinethy!]phenoxyacetic acid (M.P. 169-172°C) CALC; C, 72.28; H, 5.10; N, 3.37 FOUND: C, 69.34, 69.69; H, 5.10, 5.13; N, 3.00, 3.08 C.\LC-. C, 69.27; H. 5.35; N. 3.23 (as Hydrate) 2-[4-(2-Quinoiinylmethyioxy)phenoxymethyl]cinnamic acid (M.P- 175-178°C) CALC: C, 75.90; H. 5.14; N, 3.40 FOUND: C, 73.92; H. 5.20; N, 3.01 CALC: C. 74.27: H. 5.27; N.3.33 (as Hydraie) 6-Acetyl-2-propyi-3-[3-{2-quinolinylmethyloxy)-benzyioxy]phenoxyacetic acid (M.P. I53-5S°C) CALC: C, 72.13; H, 5.85: N, 2.90 FOUND: C, 71.68, 72.08; H, 5.88, 5.83: R 2.65, 2.70 2-[2-{4-(7-Chloroqiiinoiin-2-ylmethyloxy)-phenoxymelhyl)phenoxyjpropionic acid (M.P. 169-173'*C) CALC: C, 67.32; H, 4.78; N, 3.02; CI, 7.64 FOUND: C, 65.18; H, 4.90; N, 2.84; CI, 8.33 CALC: C, 65.41; H, 4,96; N, 2.93; CI, 7,42 (as HYDRATE) 2-[4-(2-OuinoIinylmethyloxy)phenoxymethyi]phenyiacetic acid (M.P- ]81-83»C) CALC: C, 75.17; H, 5 JO; N, 3.51 FOUND: C, 75.12, 74.96; H, 5.50, 5.49; N, 3.16, 3.16 3-[3-(2-Quinolinylraetiiyloxy)phenoxymethyilphenoxyaceticacid (M.P. ]46-51°C) CALC: C, 72^8; H. 5.10; N. 3.37 FOUND: C, 71.82, 71.80; H. 5.24, 5.23; N, 2.98, 3.00 CALC: C, 7! .50; H, 5.16; N, 3.34 (as HYDRATE) 2-[4-(2-Quinolinyimethyloxy)pbenoxymethyl]phenoxyacetic acid (M.P. 153-57*C) CALC: C, 72^8; H, 5.10; N, 3 J7 FOUND: C, 72.30, 71.72; H, 5 J9, 5.30; N, 2.94, 2.89 5.[2-(4-(7-ChIoroquinoItn-2-ylmethyiQxy)-phenoxymethyI)benzyI]letrazo!e(M.P. I59-63°C) CALC: C, 65.57; H, 4.40; N, 15.29 FOUND: C, 64.16; H, 4.72; N, 14.98 CALC: C, 64.30; H, 4.53; N, 14.99 (as HYDRATE) 2-Cart>omethoxy-5-[3-(2-quinolinyImethy[oxy)-phenoxymethyi]phenoxyacetic acid (M-P. !87-89°C) CALC: C, 68.49; H, 4.90; N, 2.95 FOUND: C, 66.71; H, 4.96; N, 2.70 CALC: C, 66.59; H, 5.07; N, 2.87(as HYDRATE) 2-[3-(2-Qu!noiinylmethyioxy)phenoxymethy[]-6-methyiphenoxyacciic acid (M.P. !49-53°C) CALC; C, 72.71; H. 5.40; N. 3.26 FOUND: C, 71.23: H. 5.46; N, 3.08 CALC; C, 7L22; H. 5.51; N, 3.19 (as HYDRATE) 2-[j-(j-(2-Ouinoiinyimethyloxy)phenoxymethyl)phenoxy]gluiaric acid (M.P. 129-30'C) CALC; C, 69.00: H, 5.1 7; N, 2.87 FOUND: C, 58.19; H, 4.93; N, 2.23 CALC: C, 58.23; H, 5.1 7; N, 2.43 (as HYDRATE) 2-[3-(2-Quinoiinylmethyioxy)phenoxymethyI]benzylmaionic acid (M.P. !64-65°C) CALC: C, 70.89; H, 4.08; N, 3.06 FOUND: C, 70.51, 70.61; H, 5.03, 5.24; N, 3.03, 2.90 2-[2-(3-(2-Quinormylniethyloxy)phenoxymethyl)phenoxy]pentanoic acid (M.P. n8-20X) CALC: C, 73.51; H, 5.95; N, 3.06 FOUND: C, 73.26; H, 6.07; N, 2.79 2-[4-(2-Quinoiinylmelhyloxy)phenoxytnethyl]-6-methylphenoxy acetic acid (M.P.- 151-S3'C) CALC: C, 72.71; H, 5.40; N, 3.26 FOUND: C, 71.41; H, 5.58;N, 3.Q3 CALC: C, 71.22; H, 5.5 i; N, 3.19 (as HYDRATE) 2-[2-(4-(2-QuinoIinylmethyloxy)phenoxymethy!)phcnoxy}pentanoic acid (M.P. 85-92°C) CALC: C, 73.51; H, 5.95; N, 3.06 FOUND: C, 71.73, 71.79; H, 5.96, 5.91; N, 3.06, 2.83 CALC: C, 72.09; H, 6.05; N, 3.00 (as HYDRATE) I 2-Carbomethoxy-5-[4-(2-quinolinyImethyloxy)-phenoxymethyI]phenoxyacetic acid (M.P. 149-51°C) CALC: C, 68.49; H, 4.90; N, 2.95 FOUND: C, 68.00, 68.08; H, 4.98, 5.04; N, 2.90, 2.90 2-[2-(4-(2-QuinoiinyImethyloxy)phenoxymethylphenoxy]propionic acid (M.P. 161-64°C) CALC: C, 72.71; H, 5.40; N, 3.26 FOUND: C, 70.96, 7i.l0; H, 5.51, 5.58; N, 3.08, 3.10 CALC: C, 71.22: H, 5.52; N, 3.19 (as HYDRATE) 2-[2-(3-(2-Qijinolinylmetliyioxy)phenoxymethyI)phenoxy]glutaric acid (M.P. 83°C dec) CALC: C. 68.98; H, 5.17; N. 2.87 FOUND: C. 64.10, 63.75; H. 4.39, 4.92: N. 2.64. 2.69 CALC: C, 63.74; H. 5.63; N, 2.65(as HYDRATE) 2-('3-[2-Quinolinyimethyloxy]benzyloxy)phenoxyacEtic acid (M.P. 153-55°C) CALC: C, 72.28; H. 5.10; N. 3.37 FOUND: C, 71.75; H, 5.M; N. 3.38 CALC: C, 71.50; H. 5.16; N. 3.34 (as HYDRATE) 2-(2-f4-(2-Quino(iny)metfiyloxy)phenoxyraethy(]-4chlorophenoxy)propionic acid (M.P. i96-99°C} CALC: C, 67.32; H, 4.78; N, 3.02 FOUND: C, 67.40, 67.43; H, 4.89, 4.94; N, 3.01, 3.13 2-{2-[3-(2-QuinoIinylmethyloxy)phenoxymethyl]-4chiorophenoxy)propionic acid (M.P. 169-7I'C) CALC: C, 67.32; H, 4,78; N, 3.02 FOUND: C, 65.47; H, 5.31; N, 2.78 CALC: C, 65.41; H, 4.96; N, 2.93 (as HYDRATE) 2-(2-[3-(2-Quinolinyimethy]oxy)phenoxyniethyl]-4chlorophenoxy)pentanoic acid (M.P. 144-45°C) CALC: C, 68.36; R 5,33; N, 2.85 FOUND: C, 67.74, 67.86; H, 5.39, 5.47; N, 2.91, 2.84 CALC: C, 67.74; H, 5 J8; N, 2.82 (as HYDRATE) 2-(2-[4-(2-Quino[inylmethyloxy)phenoxymethy!]-4-ch!orophenoxy)pentanoic acid (M.P. 155-56°C) CALC: C, 68.36; H, 5.33; N, 2.85 FOUND: C, 65.96; H, 5.59; N, 2.66 CALC: C. 65.95; H, 5.53; N. 2.75 (as HYDRATE) 2-(2-[4-(2-Quinolinyimethylaxy)phenoxymethyl]-4-chlorophenoxy)pentanoic acid {M.P. ]55-56°C) CALC: C, 6836; H, 5.33; N, 2.85 FOUND: C, 66.15; H, 5.58; N, 2.68 CALC: C, 65.95; H, 5.53; N, 2.75 (as HYDRATE) 2-(2-[4-(2-Ouinolinyimethyioxy)phenoxymethyl]-6-chiorophenoxy)pentanoic acid (M.P. 161-62°C) CALC: C, 6&36; H, 5.33; N, 2.85 FOUND: C, 68.15; H, 5.36: N, 2.72 2-(2-[3-(2-Ouinolinylmeihyioxy)phenoxynie[hyl]-6-chiorophenoxyjpentanoic acid (M.P. 169-70°C) CALC: C, 6836; H, 5.33; N, 2.85 FOUND: C, 68.10; H, 5.39; N, 2.72 2-(2-[3-(2-Quinoiinyimettiyloxy)phenoxymethyi]-6-chlQrophenoxy)-4-methyipenianoicacid (M.P. 164-66°C) CALC: C, 68.84: H, 5.58; N, 2.77 FOUND: C, 68.84; H, 5.70; N, 2.69 2-(2-[4-(2-Quinolinylmethyloxy)phenoxymethyl]-6-chlQrophenoxy>-4-inethyipentanoicacid (M.P. !67-69=C) CALC: C, 68.84; H, 5.58; N, 2.77 FOUND: C, 68.78; H, 5.67; N, 2-68 5-[3-(3-(2-quinoIinylmethy!oxy)benzyloxy>-4-methoxyphenyl]tetrazoie(M.P. 204-07'C) CALC: C, 67.63; H, 4.88; N, 15.78 FOUND: C, 67.11; H, 5.15; N, 15.86 N-[3-Methoxy-4-(3-(2-quinofinyimethy(oxy)benzyioxy)faenzoyI)benzene suifonamide hydrochloride (M.P. dec.88) CALC: C, 62.99; H, 4.60; N, 4.74 FOUND: C, 63.88; H, 5.13; N, 4.80 5-Carboxy-2-(3-(2-quinoiinylmethy{oxy)phenoxym«hyi)phenoxy acetic acid (M.P. 216'2Z°C) CALC: C, 61.90; H, 5.18; N, 2.77 FOUND: C, 61.62; H, 5.11; N, 2.67 5-[3-Methoxy-4-(3-(2-quinolinyimethyloxy)benzyioxy)phenyl]tetra2o!e (M.P. 204-05"*C) CALC: C, 67.67; H, 5.14; N, 15.87 FOUND: C, 67.63; H, 4.88; N, 15.78 5-(4-(3-(2-QuinoIinylmethyioxy)ben2yioxy)phenyl)tetra2ole(M.P. 233-36°C) CALC: C, 69.58; H, 4.73; N, 16.91 FOUND: C, 69.59; H, 4.89; N, 16.91 Using a combination of the above Examples, various compounds may be made within the scope of this invention. Compounds according to the invention exhibit marked pharmacological activities according to tests described rn the literature which tests results are believed to correlate to pharmacoiogical activity in humans and other mammals. The following phamiacological test results are typical characteristics of compounds of the present invention. The compounds of the present invention have potent activity as PPAR ligand receptor binders and possess ant}-dJabet)C, anti-ljpidemic, anli-hyperlensive, and anti-arteriosclerotic activity and are also anticipated to be effective in the treatment of didwtes, obesity and other related diseases. hPPARcc Binding Assay Tbeactiviiy of the compounds ofthe invention as PPARa modulators may be examined in several relevant in vitro and in vivo preclinical assays, for example benchmarking with a known PPARct moduialor, for example, pH]-GW233U2-C4-[2-{3-[2,4-Difluoropbenj')}-I-beply]ureido>ethyJ}phenoxy>-2-methyIbutyric acid). (S. Kliewer, et al. Proc. Natl. Acad. Sci. USA 94 (1997). Humanperoxime proUferator-activated receptor a ligand binding domain(hPPARa.-LBD)'. A binding assay for PPARa could be carried out by the following procedure: cDNAs encoding the putative ligand binding domain of human PPARa (amino acids ] 67-468) ( Sher,T., Yi, H.-F., McBride, O. W.& Gonzaiez, P. i. {\997i) Biochemi3iry22, 5598-5604) are amplified by PCR (Polymerase Chain Reaction) and inserled in frame into the BamHI site of pGEX-2T oiasmid (Pharmacia). The Soluble fraction of GST-hPPARa fusion proteins or gluathione S-transferase (GST) alone are overexpressed in £ coU BL21fDE3)pLysS celis and purified from bacteria extracts as described in {S. Kliewer, et al. Proc. Natl. Acad. Sci. USA 94 (1997), 4318-4323). Gel-Fiitration Assays: 30 ml of 90 nM GST-hPPARa-LBD is mixed with 20 ml of 50 nM 'H-GW2331 with or without 5 ml of 10 mM test compounds in the binding buffer containing i 0 mM Tris. 50 mM KCl, 0.05% Twcen 20 and 10 mM DTT. The reaction mixtures are incubated in 96-well plates for 2h at room temperature. 50 ml of the reaction mixtures are then loaded on a 96-well gel filtration block (following manufacture instructionsXEdgeBioSyslems). The block placed on top of a clean 96-weH plate is centrifueed at 1,500 rpm for2 min. The block is discarded. 100 mi of Scintillation fluid is added to each well of the 96-well plate. After overnight equilibration, the plate is counted in the Microbeta counter (Wallac). Homogenous Scintillation Proximity Binding Assay. For the Scarchard analysis, glutathione coated SPA beads (1.5 mg/ml XAraersham) are mixed with GST-hPPARcc-LBD (10 mg/ml) in the binding buffer. The resuiting slurry is incubated at room temperature with agitation for 15 min. 20 ml of the SIUTT>' is then added in 30 ml of binding buffer containing various amount 'H-GW2331(10-500 nM). Nonspecific binding is determined in the present of 100 mMof GW2331. For the competition binding assay, 20 ml of ^e slurry is then added in 30 mi of the binding buffer containing 75 nM of ^H-GW233i and 0.03-20 mM ofihe test compounds. For the control experiments, the glutathione coated SPA beads (1.5 mg/ml) are coated with GST proteins (10 mg/ml). 20 ml of the slurry are mixed with 30 ml of 75 nM of ^H-GW233I with or without 10 mM of GW2331. The above experimenli are al! performed in a 95-wel\ plates. Tht sealed plates with the reaction mixtures are allowed to equilibrate for 2 h and counted in the Microbeta counter (Wallac.). hPPARY Binding Assay The activity of the compounds of the invention as PPARj modulators may be examined in several relevant in vitro and in vivo preclinical assays, for example benchmarking with a known PPARj modulator, for example, ['H]-BRL 49853 (Lehman L.J. et aL J. Biol. Chem. 270, 12953-12956; Lehman L.J. et al, J. Biol. Chem. 272, 3406-3410(1997), and Nichols, J. S.; et al Analytical Biochemistry 257, 112-119(1998)). Human peroxime projiferator-activated receptor a ligand binding domain(hPPARv-LBD). A binding assay for PPARy could be carried out by the foiiowing procedure: cDNAs encoding the puiaiive ligand binding domain of human PPARy (amino acids 176-477) (Green, M,E. el al- Gene expression 281 -299{ i 995)) are amplified by PCR (polymerase chain reaction) and insened in frame into the BamHI site of pGEX-2T plasmid (Pharmacia). The soluble fraction of GST-hPPARy fusion proteins or glutathione S-transferase (GST) atone are overexpressed in £. coH BL2t(I>E3)pLysS cells and purified from bacteria extracts. Binding Assay: The fusion proteins, GST-PPARy-LBD in PBS (5 mg/IOOmfwell) are incubated in the glutathione coated 96 well plates for 4 hours. Unbound proteins are then discarded and the plates are washed two times with the wash buffer (10 mM Iris, 50 mM KCl and 0.05% Tween-20). 100 ml of reaction mixtures containing 60 nM of ■'H-BRL-49853 and !0 mM of the testing compounds (10 mi of O.ImM compounds from each well of the child plates) in the binding buffer (lOmM Tris, 50mM KCl and lOmM DTT) are then added and incubated at room temperature for 2.5h. The reaction mixtures are discarded and the plates are washed two times with the wash buffer. 100ml of scintillation fluid is added to each well and plates are counted on p-counter. hPPARS Binding Assav The activity of the compounds of the invention as PPAR5 modulators may be examined in several relevant in vitro and in vivo preclinical assays (See references WO 97/28149; Brown P. et ai Chemistp/ &. Biology, 4,909-18, (1997)), for example benchmarking wiiii aknown PPARS modulator, for example [^H.] GW2433 or f^H,] Compound X The hPPARo binding assay comprises the steps of: (a) preparing multiple test samples by incubating separate aliquois of the receptor HPPARS with a test compound in TEGM containing 5-10% COS-1 cell cytoplasmic lysate and 2.5 nM labeled (['H]Compound X. 1 7 Ci/mmol) for a minimum of 12 hours, and preferably for about 16 hours, at 4'C, wherein the conceniration of the test compound in each test sample is different, and preparing a control sample by incubating a further separate aliquot of the receptor hPPARo under the same conditions but without the lest compound: then (b) removing unbound ligand by adding dextran/geiaTin-coated charcoal lo each sample while maintaining the samples at 4°C and allowing at least 10 minutes to pass, then (c) subjecting each of the test samples and control sample from step (b) to cenlrifijsalion ar4°C umil the charcoal is pelleted: then (d) counting a portion of the supernatant fraction of each of the test samples and the control sample from step (c) in a liquid scinitillation counter and analyzing the results to determine the ICso of the test compound. In the hPPARS binding assay, preferably at least four test samples of varying concentrations of a single test compound are prepared in order to determine the IC50. The compounds useful according to the invention can be administered to a patient in a variety of forms adapted to the chosen route of administration, i.e., orally, or parenterally. Parenteral administration in this respect includes administration by the following routes: intravenous, intramuscuiar, subcutaneous, intraocuiar, intrasynovial, transepthelially including transdermal, opthalmic, sublingual and buccal; topically including opthalmic, dermal, ocuiar, recial and nasal inhalation via insufHation and aerosol and rectal systemic. The active compound may be orally administered, for example, with an inert diluent or with an assimilable edible carrier, or it may be enclosed in hard or soft shell gelatin capsules, or it may be compressed into tablets, or it may be incorporated directly with the food of the diet For oral therapeutic administration, the active compound may be incorporated with excipient and used in the form of ingestible tablets, buccal tablets, troches, capsules, elixirs, suspensions, syrups, wafers, and the like. Such compositions and preparations should contain at least 0.1% of active compound. The percentage of the compositions and preparations may, of course, be varied and may conveniently be from about 2% to about 6% of the weight of the unit. The amount of active compound in such therapeutically useful compositions is such that a suitable dosage will be obtained. Preferred comfrasitions or preparations according to the present invention are prepared so that an oral dosage unit form contains between about 50 and 300 mg of active compound. The tablets, troches, pills, capsules and the like may also contain the following: A binder such as gum tragacanth. acacia, com starch or gelatin; excipients such as dicalcium phosphate; a disintegrating agent such as com starch, potato starch, alginic acid and the like: a lubricant such as magnesium stearate; and a sweetening agent such as sucrose, lactose or saccharin may be added or a flavoring agent such as peppermint, oil of winiergreen. or cherr\' flavoring. When the dosage unit form is a capsule, it may contain, in addition to materials of the above tyoe. a liauid carrisr. Various other materials may be present as coatings or to otherwise modify the physical form of the dosage unii. For instance, tablets, pilis. or capsules may be coated with shellac, sugar or both. A syiup or elixir may contain the active compound, sucrose as a sweetening agent, methyl and propylparabens a preservatives, a dye and flavoring such as cherry or orange flavor. Of course, any material used in preparing any dosage unit fonn shc^uld be pharmaceuticaily pure and substantially non-toxic in the amounts employed, in addition, the active compound may be incorporated into sustained-release preparations and formulations. The active compound may also be administered parenlerally or intraperitoneally. Solutions of the active compound as a free base or pharmacologically acceptable salt can be prepared in water suitably mixed with a surfactant such as hydroxypropyl-cellulose. Dispersion can also be prepared in glycerol, liquid polyethylene glycols, and mixtures thereof and in oils. Under ordinary conditions of storage and use, these preparations contain a preservative to prevent the growth of microorganisms. The pharmaceutical forms suitable for injectable use include sterile aqueous solutions or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersions. In all cases, the form must be sterile and must be fluid to the extent that easy syringability exists. It may be stable under the conditions of manufacture and storage and must be preserved against the contaminating action of microorganisms such as bacteria and fiingi. The carrier can be a solvent or dispersion medium containing, for example, water, ethanoL polyol (for example, giycero;. propylene glycol, and liquid polyethylene glycol, and the like), suitable mixtures thereof, and vegetable oils. The proper fluidity can be maintained , for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of surfactants. The prevention of the action of microorganisms can be brought about by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, sorbic acid, thimerosal, and the like. In many cases, it will be preferable to include isotonic agents, for example, sugars or sodium chloride. Prolonged absorption of the injectable compositions of agents delaying absorption, for example, aluminum monostearate and gelatin. Sterile injectable solutions are prepared by incorporating the active compound in the required amount in the appropriate solvent with various of the other ingredients enumerated above, as required, followed by filtered sterilization. Generally, dispersions are prepared by incorporating the various sterilized active ingredient into a sterile vehicle which contains the basic dispersion medium and the required other ingredients from those enumerated above. In the case of sterile powders for the prepaiaiion of sterile injectable solutions, the preferred methods of preparation are vacuum drying and the freeze drying technique which yield a powder of the active ingredient plus any additional desired ingredient from previously sicrile-fitiered solution thereof. The therapeutic compounds useful according to this invention may be administered to s patient aione or in combination with pharmaceuticatly acceptable carriers, as noted above, the proportion of which is determined by the solubility and chemicai nature of the compound, chosen route of administration and standard pharmaceutical practice. The physician will determine the dosage of the present therapeutic agents which will be most suitable for prophylaxis ortreatmeni and it will vary with the form of administration and the particular compound chosen, and also, it will vary with the panicutar patient under treatment. He wil) generally wish to initiate treatment with small dosages by small increments until the optimum effect under the circumstances isreached. The therapeutic dosage will generally be from 0.1 to 100 mM/day or from about O.Jmg to about 50 mg/kg of body weight per day, or lOmgto about 50 mg/kg of body weight per day, or more preferably 30mg ID about 50 mg/kg of body weight per day, and higher, atthou^ it may be administered in several different dosage units. Higher dosages are required for oral administration. The compounds usefiji according to the invention may be administered as frequently as necessary in order to obtain the desired therapeutic effect. Some patients may respond rapidly to a higher or lower dose and may find much weaker maintenance doses adequate. For other patients :: may be necessary to have long-term treatments at the rate of 1 to 4 doses per day, in accordance with the physiological requirements of each particular patient. Generally, the active product may be administered orally 1 to 4 times per day. It goes without saying that, for other patients, it will be necessary to prescribe not more than one or two doses per day. One skilled in the art wii! readily appreciate that the present invention is weiladapted to carry out the objects of the invention and obtain the ends and advantages mentioned, as well as those inherent therein. The compounds, compositions and methods described herein are presented as representative of the preferred embodiments, or intended to be exemplary and not intended as limitations on the scope of the present invention. WE CLAIM: 1. A compound of formula I is quinoxalinyl, quinazolinyl, benzoxazolyl, benzimidazolyl, benzothiazolyl, benzofliranyl, benzothiophenyl, oxazolyl, thiazolyl, oxadiazolyl, isoxazolyl, imidazolyl, pyrazolyl, thiadiazolyl, triazolyl, pyridyl, pyrimidinyl, pyrazinyl or pyridazinyl, which is optionally substituted by one or more ring system substituents; are, independently, aryl, which are optionally substituted by one or more ring system substituents; A is -0-, -S- -SO-, -SOr-, -NR13- -C{0)-, -N{R,4)C(0)-, -C(0)N(Rs) -, -N(R,4)C{0)N{Ri5)-, -C(R,4)==N-, a chemical bond, 211 B is -0-, -S-, -SO-, -SO2-, ethynylene, -C(0>-, -N(Ri8)C(0)-, or - C(0)NR!8-; D is -0-, -S-, -NR|9-, a chemical bond, ethynylene, - N(R2o)C{0)-, -C(0)-, or -C{0)N(R2o)-; E is a chemical bond or an ethylene group; a is CM; bis 0-4; c is 0-4; d is 0-5; e is 0-4; f is 0-6; g is 1-4; h is 1-J; Ri, R3, R5, R7, Kg, and R,i, are independently hydrogen, halogen, alkyl, carboxyl, alkoxycarbonyl or aralkyi; R2, R4, ^6, Ra* R-io and R12, are independently -(CHi^-X; q is 0-3; X is hydrogen, halogen, alkyl, alkenyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, aralkyi, heteroaralkyl, hydroxy, alkoxy, aralkoxy, heteroaralkoxy, carboxyl, alkoxycarbonyl, tetrazojyl, acyl, acylHNSO^-, -SR23, Y'Y^N- or Y^VNCO-; Y' and Y are independently hydrogen, alkyl, aryl, aralkyl or heteroaralkyl, or one of Y' and Y^ is hydrogen or alkyl and the other of Y' and Y^ is acyl or aroyi; Y^ and Y"* are independently hydrogen, alkyl, aryl, aralkyl or heteroaralkyl; Z is R21O2C- R21OC- cyclo-hnide, -CN, R21O2SHNCO-, R2,02SHN-, (R2i)2NCO-, R2iO-2,4-thiazolidinedionyl, or tetrazolyl; and R21 is hydrogen, alkyl, aryl, cycloalkyl, or aralkyl; Ri3, Ri9 and R23 are independently R22OC-, R22NHOC-, hydrogen, alkyl, aryl, heteroaryl, cycloalkyl, heterocyclyl, heteroaralkyl, or aralkyl; Rt4, Ris, Ri6, R18 and R20 are independently hydrogen, alkyl, aralkyl, carbonyl, or alkoxycarbonyl; or Ri4, and R[5 taken together with the carbon and nitrogen atoms through which they are linked form a 5 or 6-menibered azaheterocyclyl group; and R22 is hydrogen, alkyl, aryl, heteroaryl, cycloalkyl, heterocyclyl, heteroaralkyl, or aralkyl; or a pharmaceutically acceptable salt thereof, an N-oxide thereof, a hydrate thereof or a solvate thereof; wherein "alkyl," when used to designate an alkyl group per se or when used as an alkyl component of any other group, is an aliphatic hydrocarbon group which is straight or branched having 1 to 20 carbon atoms and is optionally substituted by one or more alkyl group substituents; "aryl" is an aromatic monocyclic or multicyclic ring system of 6 to 14 carbon atoms, which is optionally substituted by one or more ring system substituents; "heteroaryl" is an aromatic monocyclic or multicyclic ring system of 5 to 14 carbon atoms, in which at least one of the carbon atoms in the ring system is replaced by nitrogen, oxygen or sulfur, which is optionally substituted by one or more ring system substituents; "heterocyclyl" is a non-aromatic saturated monocyclic or multicyclic ring system of 3 to 10 carbon atoms, in which at least one of the carbon atoms in the ring system is replaced by nitrogen, oxygen or sulfur, which is optionally substituted by one or more ring system substituents; "heteroaralkyl" is a heteroaryl-alkyl group, wherein the heteroaryl and alkyl groups are as defined above; an "alkyl group substituent" is halo, carboxy, cycloalkyl, cycloalkenyl, heterocyclyl, heterocyclenyl, aryl, alkoxy, alkoxycarbonyl, aralkoxycarbonyl, heteroaralkoxycarbonyl, or Y'Y^NCO-, wherem Y' and Y^ are independently hydrogen, alkyl, aryl, aralkyl or heteroaralkyl, or Y' and Y^ taken together with the nitrogen atom to which Y' and Y^ are attached form heterocyclyl wherein the substituents may contain further alkyl group substituents or ring system substituents as recited herein; and a "ring system substituent" is alkyl, cycloalkyl, heterocyclyl, aiyl, heteroaryl, aralkyl, heteroaralkyl, hydroxy, alkoxy, aryloxy, aralkoxy, acyl, aroyl, halo, nitro, cyano, carboxy, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, alkylsulfonyl, aiylsulfonyl, heteroarylsulfonyl, alkylsulfmyl, arylsulfinyl, heteroarylsulfmyl, alkylthio, arylthio, heteroaiylthio, aralkylthio, heteroaralkylthio, fiised cycloalkyl, fused cycloalkenyl, fused heterocyclyl, fused heterocyclenyl, arylazo, heteroarylazo, R'R'^-, R'R'^CO-, R'OZCN-, or R'^R'^NS02- wherein R* and R** are mdependently hydrogen, alkyl, aryl, aralkyl or heteroaralkyl, or one of R" and R' is hydrogen or alkyl and the other of R^ and R' is aroyl or heteroaroyl, and R*^ and R*" are independently hydrogen, alkyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocyclyl, heterocyclenyl, aralkyl or heteroaralkyl and, where the ring is cycloalkyl, cycloalkenyl, heterocyclyl or heterocyclenyl, the ring system substituent may also include methylene, oxo and thioxo on carbon atoms thereof wherein the substituents may contain further alkyl group substituents or ring system substituents as recited herein. The compound as claimed in claim 1, wherein is optionally substituted quinoxalinyl, quinazolinyl, benzoxazolyl, benzimidazolyl, benzothia^olyl, oxazolyl, thiazolyl, oxadiazolyl, isoxazolyl, imidazolyl, pyrazolyl, thiadiazolyl, triazolyl, pyridyl, pyrimidinyl, pyrazinyl or pyridazinyl. The compound as claimed in claim 1, wherein a=l, 2 or 3; Ri and R2 are hydrogen; A is -0-; and b=0. The compound as claimed in claim 1, wherein c=0 or 1; Rj and R6 are hydrogen; B is -0-; and d=0 or 1. The compound as claimed in claim 1, wherein e=0; f=0 or 1; D and E is a chemical bond; Z is tetrazolyl, NH2CO- or -CO2R21; and R21 is hydrogen or lower alkyl. The compound as claimed in claim 1, wherein e=0; f=0 or 1; D is -O- or a chemical bond; E is a chemical bond; and Z is tetrazolyl, NH2CO- or -CO2R21; and R21 is hydrogen or lower alkyl. The compound as claimed in claim 1, wherein is an unsubstituted quinozalin-2-yl, 3-substituted quinozalin-2-yl, 6-substituted quinozalin-2-yl or 3,6-disubstituted quinozalin-2-yl; unsubstituted quinazolin- 2-yl, 4-substituted quinazotin-2-yl or 6-substituted quinazolin-2-yl; 2- substituted-oxazol-4-yl or 2,5 disubstituted-oxazol-4-yl; 4-substituted oxazol-2- yl or 4,5-disubstituted-oxazol-2-yl; 2-substituted thiazol-4-yl or 2,5- disubstituted thiazol-4-yl; 4-substituted thiazol-2-yl or 4,5-disubstituted- thiazol-2-yl; 5-substituted-[l,2,4]oxadiazol-3-yl; 3-substituted- [l,2,4]oxadiazol-5-yl; 5-substituted-imidazol-2-yl or 3,5-disubstituted-imidazoJ-2-yJ; 2-substituted-imidazoJ-5-yi or 2,3-disubstituted-imidazoI-5-yI; 3-substituted-isoxazol-5-yl; 5-substituted-isoxazol-3-yi; S-substituted-[l,2,4] thiadiazol-3-yl; 3-substituted-[l,2,4]-thiadiazol-5-yl; 2-substituted-[l,3,4]-thiadiazol-5-yl; 2-substituted-[l,3,4]-oxadiazol-5-yl; l-substituted-pyrazol-3-yl; 3-substituted-pyrazol-5-yl; 3-substituted-[l,2,4]-triazol-5-yl; 1-substituted-[l,2,4]-triazoI-3-yl; 3-substituted pyridin-2-yl, 5-substituted pyridin-2-yl, 6-substituted pyridin-2-yl or 3,5-disubstituted pyridin-2-yl; 3-substituted pyrazin-2-yl, 5-substituted pyrazin-2-yl, 6-substituted pyrazin-2-yl or 3,5 disubstituted-pyrazin-2-yl; 5-substituted pyrimidin-2-yl or 6-substituted-pyrimidin-2-yl; 6-substituted-pyridazin-3-yl or 4,6-disubstituted-pyridazin-3-yl; unsubstituted-benzothiazol-2-yl or 5-substituted-benzothiazoI-2-yl; unsubstituted benzoxazol-2yl or 5-substituted-benzoxazol-2yl; unsubstituted-benzimidazol-2-yl or 5-substituted-benzimidazol-2-yt; unsubstituted-thiophen-2-yl, 3-substituted-thiophen-2-yl, 6-substituted-thiophen-2-yl or 3,6-disubstituted-thiophen-2-yl; unsubstituted-benzofuran-2-y, 3-substituted-benzofliran-2-yl, 6-substitui:ed-benzofijran-2-yl or 3,6-disubstituted-benzofixran-2-yl; S-substituted-benzofuran-6-yl or 3,7-disubstituted-benzofLiran-6-yl. The compound as claimed in claim 7, wherein is substituted by a substituent selected from the group consisting of phenyl, substituted-phenyl, thienyl, substituted thienyl, cycloalkyi, straight or branched lower alkyl, fluoro, chloro, alkoxy, aralkyloxy, trifluoromethyl and trifluoromethyloxy. The compound as claimed in claim 1, wherein R| and R2 are hydrogen; a=l; A is -0-; and b=0. A compound of formula (la) wherein: is quinoxalinyl, quinazolinyl, benzoxazolyl, benzimidazolyl, benzothiazolyl, benzofuranyl, benzothiophenyl, oxazolyl, thiazolyl, oxadiazolyl, isoxazolyl, imidazolyl, pyrazolyl, thiadiazolyl, triazolyl, pyridyl, pyrimidinyl, pyrazinyl or pyridazinyl, which is optionally substituted by one or more ring system substituents; is aryl, which is optionally substituted by one or more ring system substituents; A is -0-, -S-, -SO- -SO2- -NR,3- -C(0)-, -N(R,4)C(0)-, -C(0)N(R,sK -N(Ri4)C(0)N(R,5)-, -C(R,4)==N- a chemical bond, B is -0-, -S- -SO-, -SO2- ethynylene, -C{OK -N(R,8)C(0)-, or -C{0)NR,8-; D is -0-, -S-, -NR,9-, a chemical bond, ethynylene, -N(R2o)C(0)-, -C{0)-, or-C(0)N(R2oH E is a chemical bond or an ethylene group; a is 0-4; bis 0-4; cis 0-4; d is 0-5; e is 0-4; f is 0-6; g is 1-4; hisl^; Ru R3, R5, R7, R9, and Rn, are independently hydrogen, halogen, alkyl, carboxyl, alkoxycarbonyl or aralkyl; R2, R4, Re, Rg, Rio and Rn, are independently -{CH2)q-X; q is 0 3; X is hydrogen, halogen, alkyl, alkenyl, cycloalkyl, heterocyclyl, aryl, heteroaiyJ, aralkyl, heteroaraikyi, hydroxy, alkoxy, aralkoxy, heteroaralkoxy, carboxyl, alkoxycarbonyl, tetrazolyl, acyl, acylHNS02-, -SR23, Y'Y^N- or Y^r^CO-; Y' and Y^ are independently hydrogen, alkyl, aiyl, aralkyl or heteroaraikyi, or one of Y' and Y^ is hydrogen or alkyl and the other of Y' and Y^ is acyl or aroyl; Y^ and Y' are mdependently hydrogen, alkyl, aryl, aralkyl or heteroaraikyi; Z is R21O2C- R21OC-, cyclo-hnide, -CN, R21O2SHNCO-, R21O2SHN- (R2i)2NCO-, R2iO-2,4-thiazolidinedionyl, or tetrazolyl; R' and R" are, independently, hydrogen or ring system substituents; R21 is hydrogen, alkyl, aryl, cycloalkyl, or aralkyl; Ri3, Ri9 and R23 are independently R22OC-, R22NHOC-, hydrogen, alkyl, aryl, heteroaryl, cycloalkyi, heterocyclyl, heteroaraUcyl, or aralkyi; Ri4, Ri5, Ri6> R18 and Rao are independently hydrogen, alkyl, aralkyi, carbonyl, or alkoxycarbonyl; or Ri4, and R15 taken together with the carbon and nitrogen atoms through which they are linked form a 5 or 6-membered azaheterocyclyl group; and R22 is hydrogen, alkyl, aryl, heteroaryl, cycloalkyi, heterocyclyl, heteroaralkyl, or aralkyi; or a pharmaceutically acceptable salt thereof, an N-oxide thereof, a hydrate thereof or a solvate thereof; wherein "alkyl," when used to designate an alkyl group per se or when used as an alkyl component of any other group, is an aliphatic hydrocarbon group which is straight or branched having 1 to about 20 carbon atoms and is optionally substituted by one or more alkyl group substituents; "aryl" is an aromatic monocyclic or multicyclic ring system of about 6 to about 14 carbon atoms, which is optionally substituted by one or more ring system substituents; "heteroaryl" is an aromatic monocyclic or multicyclic ring system of about 5 to about 14 carbon atoms, in which at least one of the carbon atoms in the ring system is replaced by nitrogen, oxygen or sulfur, which is optionally substituted by one or more ring system substituents; "heterocyclyl" is a non-aromatic saturated monocyclic or multicyclic ring system of 3 to about 1.0 carbon atoms, in which at least one of the carbon atoms in the ring system is replaced by nitrogen, oxygen or sulfur, which is optionally substituted by one or more ring system substituents; "heteroaralkyl" is a heteroaryl-alkyl group, wherein the heteroaryl and alkyl groups are as defined above; an "alkyl group substituent" is halo, carboxy, cycloalkyl, cycloalkenyl, heterocyclyl, heterocyclenyl, aryl, alkoxy, alkoxycarbonyl, aralkoxycarbonyl, heteroaralkoxycarbonyl, or Y'Y^NCO-, wherein Y' and Y^ are independently hydrogen, alkyl, aryl, aralkyl or heteroaralkyl, or Y' and Y^ taken together with the nitrogen atom to which Y' and Y^ are attached form heterocyclyl wherein the substituents may contain further alkyl group substituents or ring system substituents as recited herein; and a "ring system substituent" is alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, aralkyl, heteroaralkyl, hydroxy, alkoxy, aryloxy, aralkoxy, acyl, aroyi, halo, nitro, cyano, carboxy, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, alkylsulfinyl, aiylsulfmyl, heteroarylsulfinyl, alkylthio, arylthio, heteroarylthio, aralkylthio, heteroaralkylthio, fused cycloalkyl, fused cycloalkenyl, fused heterocyclyl, fused heterocyclenyl, arylazo, heteroaiylazo, R'R*^-, R'R'^CO-, R'OjCN-, or R*'R'NS02- wherein R* and R** are independently hydrogen, alkyl, aryl, aralkyl or heteroaralkyl, or one of R° and R^ is hydrogen or alkyl and the other of R" and R" is aroyl or heteroaroyl, and R" and R** are independently hydrogen, alkyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocyclyl, heterocyclenyl, aralkyl or heteroaralkyl and, where the ring is cycloalkyl, cycloalkenyl, heterocyclyl or heterocyclenyl, the ring system substituent may also mclude methylene, oxo and thioxo on carbon atoms thereof wherein the substituents may contain further alkyl group substituents or ring system substituents as recited herein. 11. The compound as claimed in claim 10, wherein a=l or 2; A is -0-; b=0; Rj, Ri, R? and Rg are independently hydrogen; is optionally substituted phenyl; c=0; B is -0-; d=l; e=0; f^O; D and E are a chemical bond; R' is hydrogen, halo or benzyloxy; R" is lower alkyl; Zis-COiH. 12. The compound as claimed in claim 10, wherein: a=l; A is -0-; b=0; c=0-l; B is -0-; d=0 or 1, wherein c+d=l or 2; e=0; ^0; D and E are a chemical bond; R' is hydrogen, aralkoxy, or halo; R" is lower alkyl; Z is -CO2H. 13. The compound as claimed in claim 10, wherein: a=l; A is -0-; b=0; c=0; Bis-0-;d=l; e=0; f^O; D and E are a chemical bond; R' is hydrogen; R" is lower alkyl; Z is -CO2H. 14. The compound as claimed in claim 10, wherein: a=l; A is -0-; b=0; c=0; B is -0-; d=l; e=0; D and E are a chemical bond; R' is hydrogen; R" is methyl; Z is -CO2H. 15. The compound as claimed in claim 10, wherein: is optionally substituted quinoxalinyl, quinazolinyl, benzoxazolyl, benzimidazolyl, benzothiazolyl, oxazolyl, thiazolyl, oxadiazolyl, isoxazolyl, imidazolyl, pyrazolyl, thiadiazolyl, triazolyl, pyridyl, pyrimidinyl, pyrazinyl or pyridazinyl; is optionally substituted phenyl; a=l; A is -0-; b=0; c=0; B is -0-; d=l; e=0; f^O; D and E are a chemical bond; R' is hydrogen; R" is lower alkyl; Z is CO2H. A pharmaceutical composition comprising a pharmaceutically acceptable amount of the compound as claimed in claim 1 and a pharmaceutically acceptable carrier. A pharmaceutical composition comprising a pharmaceutically acceptable amount of the compound as claimed in claim 10 and a pharmaceutically acceptable carrier. The compound as claimed in claim 1, wherein the optional ring system substituents for Ar I are selected from the group consisting of phenyl, substituted-phenyl, thienyl, substituted thienyl, cycloalkyl, straight or branched lower alkyl, fluoro, chloro, alkoxy, aralkyloxy, trifluoromethyl and trifiuoromethy loxy. The compound as claimed in claim 11, wherein R" is methyl. The compoimd as claimed in claim 12, wherein R" is methyl. The compound as claimed in claim 1, wherein the compound is or a pharmaceutically acceptable salt, hydrate or solvate thereof The compound as claimed in claim 1, wherein the compound is or a pharmaceutically acceptable salt, hydrate or solvate thereof. The compound as claimed in claim 1, wherein the compound is or a pharmaceutically acceptable salt, hydrate or solvate thereof. The compound as claimed in claim 1, wherein the compound is or a pharmaceutically acceptable salt, hydrate or solvate thereof. Dated this 23 day of October 2001

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1473-che.rtf

in-pct-2001-1473-che abstract duplicate.pdf

in-pct-2001-1473-che abstract.pdf

in-pct-2001-1473-che claims duplicate.pdf

in-pct-2001-1473-che claims.pdf

in-pct-2001-1473-che correspondence others.pdf

in-pct-2001-1473-che correspondence po.pdf

in-pct-2001-1473-che description (complete) duplicate-1.pdf

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in-pct-2001-1473-che description (complete) duplicate.pdf

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in-pct-2001-1473-che description (complete).pdf

in-pct-2001-1473-che form-1.pdf

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in-pct-2001-1473-che petition.pdf