Title of Invention	IMIDAZOLE COMPOUNDS.
Abstract	Imidazole compounds, compositions, and methods of using them in leukocyte recruitment inhibition, in modulation H4 receptor expression, and in treating conditions such as inflammation, H4 receptor-mediated conditions, and related conditions.

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Field of the Invention The invention relates to novel, pharmaceutically active, heterocyclic compounds, more particularly imidazole compounds, and methods of using them to treat or prevent disorders and conditions mediated by the histamine H4 receptor. Background of the Invention Histamine was first identified as a hormone (Barger, G. and H.H. Dale, J. Physiol. (London) 1910, 41:19-59) and has since been demonstrated to play a major role in a variety of physiological processes, including the inflammatory "triple response" via H1 receptors (Ash, A.S.F. and H.O. Schild, Br. J. Pharmac. Chemother. 1966, 27:427-439), gastric acid secretion via H2 receptors (Black, J.W. et al., Nature 1972, 236:385-390), and neurotransmitter release in the central nervous system via H3 receptors (Arrang, J.-M. et al., Nature 1983, 302:832-837) (for review see Hill, S.J. et al., Pharmacol. Rev. 1997, 49(3):253-278). All three histamine receptor subtypes have been demonstrated to be members of the superfamily of G protein-coupled receptors (Gantz. I. e tal., Proc. Natl. Acad. Sci. U.S.A. 1991, 88:429-433; Lovenberg, T.W. et al., Mol. Pharmacol. 1999, 55(6):1101-1107; Yamashita, M. et al., Proc. Natl. Acad. Sci. U.S.A. 1991, 88:11515-11519). There are, however, additional functions of histamine that have been reported, for which no receptor has been identified. For example, in 1994, Raible et al. demonstrated that histamine and R-a- methylhistamine could activate calcium mobilization in human eosinophils (Raible, D.G. et al., Am. J. Respir. Crit. Care Med. 1994, 149:1506-1511). These responses were blocked by the H3-receptor antagonist thioperamide. However, R-α-methylhistamine was significantly less potent than histamine, which was not consistent with the involvement of known H3 receptor subtypes. Therefore, Raible et al. hypothesized the existence of a novel histamine receptor on eosinophils that was non-H1, non-H2, and non-H3. Most recently several groups (Oda, T. et al., J. Biol. Chem. 2000, 275(47):36781-36786; Liu, C. et al., Mol. Pharmacol. 2001, 59(3):420-426; Nguyen, T. et al., Mol. Pharmacol. 2001, 59(3):427-433; Zhu, Y. et al., Mol. Pharmacol. 2001, 59(3):434-441; Morse, K.L. et al., J. Pharmacol. Exp. Ther. 2001, 296(3):1058-1066) have identified and characterized a fourth histamine receptor subtype, the H4 receptor. This receptor is a 390 amino acid, seven- transmembrane, G protein-coupled receptor with approximately 40% homology to the histamine H3 receptor. In contrast to the H3 receptor, which is primarily located in the brain, the H4 receptor is expressed at greater levels in eosinophils and mast cells, among other cells, as reported by Liu et al. (infra) and Hofstra et al. (J. Pharmacol. Exp. Ther. 2003, 305(3): 1212-1221). Because of its preferential expression on immunocompetent cells, this H4 receptor is closely related with the regulatory functions of histamine during the immune response. A biological activity of histamine in the context of immunology and autoimmune diseases is closely related with the allergic response and its deleterious effects, such as inflammation. Events that elicit the inflammatory response include physical stimulation (including trauma), chemical stimulation, infection, and invasion by a foreign body. The inflammatory response is characterized by pain, increased temperature, redness, swelling, reduced function, or a combination of these. Mast-cell de-granulation (exocytosis) releases histamine and leads to an inflammatory response that may be initially characterized by a histamine- modulated wheal and flare reaction. A wide variety of immunological stimuli (e.g., allergens or antibodies) and non-immunological (e.g., chemical) stimuli may cause the activation, recruitment, and de-granulation of mast cells. Mast- cell activation initiates allergic (H1) inflammatory responses, which in turn cause the recruitment of other effector cells that further contribute to the inflammatory response. The histamine H2 receptors modulate gastric acid secretion, and the histamine H3 receptors affect neurotransmitter release in the central nervous system. Modulation of H4 receptors controls the release of inflammatory mediators and inhibits leukocyte recruitment, thus providing the ability to prevent and/or treat H4-mediated diseases and conditions, including the deleterious effects of allergic responses such as inflammation. Compounds according to the present invention have H4 receptor modulating properties. Compounds according to the present invention have leukocyte recruitment inhibiting properties. Compounds according to the present invention have anti- inflammatory properties. Examples of textbooks on the subject of inflammation include Gallin, J.I. and R. Snyderman, Inflammation: Basic Principles and Clinical Correlates, 3rd Edition, (Lippincott Williams & Wilkins, Philadelphia, 1999); V. Stvrtinova, V. et al., "Inflammation and Fever", Pathophysiology Principles of Diseases (Textbook for Medical Students, Academic Press, 1995); Cecil et al., Textbook Of Medicine, 18th Edition (W.B. Saunders Company, 1988); and Steadmans Medical Dictionary. Background and review material on inflammation and conditions related with inflammation can be found in articles such as the following: Nathan, C. Nature 2002, 420:846-852; Tracey, K.J. Nature 2002, 420:853-859; Coussens, L.M. and Z. Werb, Nature 2002, 420:860-867; Libby, P. Nature 2002, 420:868-874; Benoist, C. and D. Mathis, Nature 2002, 420:875-878; Weiner, H.L. and D.J. Selkoe, Nature 2002, 420:879-884; Cohen, J. Nature 2002,420:885-891; Steinberg, D. Nature Medicine 2002, 8(11): 1211-1217. Inflammation herein refers to the response that develops as a consequence of histamine release, which in turn is caused by at least one stimulus. Examples of such stimuli are immunological stimuli and non- immunological stimuli. Inflammation is due to any one of a plurality of conditions such as allergy, asthma, chronic obstructed pulmonary disease (COPD), atherosclerosis, rheumatoid arthritis, multiple sclerosis, inflammatory bowel diseases (including Crohn's disease and ulcerative colitis), psoriasis, allergic rhinitis, scleroderma, autoimmune thyroid diseases, immune-mediated (also known as type 1) diabetes mellitus and lupus, which are characterized by excessive or prolonged inflammation at some stage of the disease. Other autoimmune diseases that lead to inflammation include Myasthenia gravis, autoimmune neuropathies, such as Guillain-Barre, autoimmune uveitis, autoimmune hemolytic anemia, pernicious anemia, autoimmune thrombocytopenia, temporal arteritis, anti-phospholipid syndrome, vasculitides, such as Wegener's granulomatosis, Behcet's disease, dermatitis herpetiformis, pemphigus vulgaris, vitiligio, primary biliary cirrhosis, autoimmune hepatitis, autoimmune oophoritis and orchitis, autoimmune disease of the adrenal gland, polymyositis, dermatomyositis, spondyloarthropathies, such as ankylosing spondylitis, and Sjogren's syndrome. Regarding the onset and evolution of inflammation, inflammatory diseases or inflammation-mediated diseases or conditions include, but are not limited to, acute inflammation, allergic inflammation, and chronic inflammation. Cited references are incorporated herein by reference. Summary of the Invention The invention features a compound of formula (I) or (II): wherein W is, independently from other member and substituent assignments, N or CR9; X is, independently from other member and substituent assignments, N or CR9; Y is, independently from other member and substituent assignments, O, NR10, or CR10R11; Z is, independently from other member and substituent assignments, N or CR12; n is, independently from other member and substituent assignments, 0, 1, or 2; each of R1-2is, independently from other member and substituent assignments, -H, -CF3, -C1-6alkyl, -C3-6cycloalkyl, optionally substituted aryl or optionally substituted heteroaryl; or, R1 and R2 taken together with the carbon atoms to which they are attached form a cyclic structure Cyc1 selected from 5- or 6-membered carbocycle, and 5- or 6-membered heterocycle with 1 heteroatom, wherein said cyclic structure Cyc1 is, independently from other substituent assignments, substituted with 0, 1, or 2 substituents selected from -C1-3alky!, halo, hydroxy, amino, and -C1-3alkoxy; each of R3-4 and R9 is, independently from other member and substituent assignments, -H, -C1-6alky!, halo, -CF3, -OCF3, -ORc, -SRC, -S(O)Rc, -SO2Rc, C1-4alkoxy, cyano, nitro, -C(O)NRaRb, -C(O)phenyl, -C(O)C1-6alkyl, -S(O)C1-4alkyl, or -SO2C1-4alkyl; or, R3 and R4 taken together with the carbon atoms to which they are attached form a cyclic structure Cyc2 selected from aryl, 5- or 6-membered carbocycle, and 5- or 6-membered heterocycle with 1 or 2 heteroatoms, wherein said cyclic structure Cyc2 is, independently from other substituent assignments, substituted with 0, 1, or 2 substituents selected from -C1-3alkyl, halo, hydroxy, amino, and -C1-3alkoxy; wherein each of Ra, Rb and Rc is, independently from other substituent assignments, selected from H, C1-4alkyl, C3-6cycloalkyl, phenyl, (C3-6cycloalkyl)C1-2alkyl-, benzyl and phenethyl, or Ra and Rb taken together with the nitrogen to which they are attached, form a 4-7 membered heterocyclic ring HetCyc1, wherein said ring HetCyc1 has 0 or 1 additional heteroatoms selected from O, S, >NH and >NC1-6alkyl, and wherein any phenyl, phenethyl, benzyl, alkyl or cycloalkyl moiety in any of said R1-4, Ra, Rb, Rc, and said ring HetCyc1 is optionally, and independently from other substituent assignments, substituted with 1, 2 or 3 substituents selected from C1-3alkyl, halo, hydroxy, amino, and C1-3alkoxy; R5 is, independently from other member and substituent assignments, -H, -C1-6alkyl, -C1-4alkoxy, or hydroxy; each of R6 and R7 is, independently from other member and substituent assignments, -H or -C1-6alkyl, or R6 and R7 taken together form a 5-6 membered cyclic structure Cyc3, wherein said cyclic structure Cyc3 is a 5- or 6-membered carbocycle or a 5- or 6-membered heterocycle with 1 or 2 heteroatoms, and wherein said cyclic structure Cyc3 is, independently from other substituent assignments, substituted with 0, 1, or 2 substituents selected from -C1-3alkyl, halo, hydroxy, amino, and -C1-3alkoxy; R8 is, independently from other member and substituent assignments, -H or -C1-4alkyl; each of R10 and R11 is, independently from other member and substituent assignments, -H or -C1-4alkyl; or, when Y is CR10R11, R10 and R11 taken together with the carbon member to which they are attached form an optionally substituted cyclic structure Cyc4, wherein said cyclic structure Cyc4 is a 3- to 6-membered carbocycle or a 3- to 6-membered non- aromatic heterocycle with 0 or 1 additional heteroatoms, or CR10R11 is C=O; R12 is, independently from other member and substituent assignments, -H, -C1-4alkyl, hydroxy, or -C1-4alkoxy; and enantiomers, diastereomers, racemates, tautomers, hydrates, solvates thereof, and pharmaceutically acceptable salts, amides or esters thereof; with the following provisos: when Y is O or NR10, then Z is CR12 and R5 is not hydroxy or -C1-4alkoxy; when Z is N, Y is CR10R11; when R1 and R2 are both -H, Y is CH2, and R8 is methyl, then R5 is not hydroxy. Embodiments of compounds of formulae (I) and (II) are modulators of the H4 receptor. Embodiments of this invention comprise mixtures of compounds of formulae (I) and (II). Isomeric forms of the compounds of formulae (I) and (II), and of their pharmaceutically acceptable salts, amides and esters, are encompassed within the present invention, and reference herein to one of such isomeric forms is meant to refer to at least one of such isomeric forms. One of ordinary skill in the art will recognize that compounds according to this invention may exist, for example, in a single isomeric form whereas other compounds may exist in the form of a regioisomeric mixture. Whether stated explicitly or not in any part of the written description and claims, it is understood that each substituent and member assignment in the context of this invention is made independently of any other member and substituent assignment, unless stated otherwise. By way of a first example on substituent terminology, if substituent S1example is one of S1 and S2, and substituent S2example is one of S3 and S4, then these assignments refer to embodiments of this invention given according to the choices S1example is S1 and S2 example is S3, S1 example is S1 and S2 example is S4; S1 example is S2 and S2 example is S3; S1example is S2 and S2example is S4; and equivalents of each one of such choices. The shorter terminology "S1example is one of S1 and S2, and S2example is one of S3 and S4" is accordingly used herein for the sake of brevity, but not by way of limitation. The foregoing first example on substituent terminology, which is stated in generic terms, is meant to illustrate the various substituent R assignments described herein. The foregoing convention given herein for substituents extends, when applicable, to members such as X, Y, Z, and W, and the index n. Furthermore, when more than one assignment is given for any member or substituent, embodiments of this invention comprise the various groupings that can be made from the listed assignments, taken independently, and equivalents thereof. By way of a second example on substituent terminology, if it is herein described that substituent Sexample is one of S1, S2, and S3, this listing refers to embodiments of this invention for which Sexample is S1; Sexample is S2; Sexample is S3; Sexample is one of S1 and S2; Sexample is one of S1 and S3; Sexample is one of S2 and S3; Sexample is one of S1, S2 and S3; and Sexample is any equivalent of each one of these choices. The shorter terminology "Sexample is one of S1, S2, and S3" is accordingly used herein for the sake of brevity, but not by way of limitation. The foregoing second example on substituent terminology, which is stated in generic terms, is meant to illustrate the various substituent R assignments described herein. The foregoing convention given herein for substituents extends, when applicable, to members such as X, Y, Z, and W, and the index n. The nomenclature "CH" with j > i, when applied herein to a class of substituents, is meant to refer to embodiments of this invention for which each and every one of the number of carbon members, from i to j including i and j, is independently realized. By way of example, the term C1-3 refers independently to embodiments that have one carbon member (C1), embodiments that have two carbon members (C2), and embodiments that have three carbon members (C3). The term Cn-malkyl refers to an aliphatic chain, whether straight or branched, with a total number N of carbon members in the chain that satisfies n ≤ N ≤ m, with m > n. When any variable referring to a substituent, compound member or index, occurs more than once, the full range of assignments is meant to apply to each occurrence, independently of the specific assignment(s) to any other occurrence of such variable. For each occurrence of a variable, it is understood that such an assignment is made independently from other member and substituent assignments. According to the foregoing interpretive considerations on assignments and nomenclature, it is understood that explicit reference herein to a set implies, where chemically meaningful and unless indicated otherwise, independent reference to embodiments of such set, and reference to each and every one of the possible embodiments of subsets of the set referred to explicitly. Any disubstituent referred to herein is meant to encompass the various attachment possibilities when more than one of such possibilities are allowed. For example, reference to disubstituent -A-B-, where A ≠ B, refers herein to such disubstituent with A attached to a first substituted member and B attached to a second substituted member, and it also refers to such disubstituent with A attached to the second substituted member and B attached to the first substituted member. The present invention also features methods for inhibiting H4 receptor activity with such compounds, pharmaceutical compositions containing such compounds, and methods of using such compositions in the treatment or prevention of conditions that are mediated by the H4 receptor, such as inflammation. Compounds according to the present invention and derivatives thereof can also be used as reference compounds in assays to assess H4 receptor modulating characteristics in light of one or more factors such as receptor inhibition, toxicity, bioavailability, and protein binding capability. Pharmaceutical compositions according to the present invention include at least one of the compounds of the present invention. If more than one of such compounds is included in a composition, the therapeutically effective amount may be a jointly effective amount. As such inhibitors of H4 receptor activity, compounds and compositions according to the present invention are useful in the prevention, inhibition, or treatment of H4 receptor-mediated conditions, such as inflammation. The invention also features a pharmaceutical composition for treating or preventing an H4 receptor-mediated condition in a subject, comprising a therapeutically effective amount of at least one H4 receptor modulator selected from compounds of formulae (I) and (II), enantiomers, diastereomers, racemates, tautomers, hydrates, solvates thereof, pharmaceutically acceptable salts, amides and esters thereof. In addition, the invention features a pharmaceutical composition for inhibiting leukocyte recruitment in a subject, comprising a therapeutically effective amount of at least one leukocyte recruitment inhibitor selected from compounds of formulae (I) and (II), enantiomers, diastereomers, racemates, tautomers, hydrates, solvates thereof, pharmaceutically acceptable salts, amides and esters thereof. The invention additionally features an anti-inflammatory composition, comprising a therapeutically effective amount of at least one anti-inflammatory compound selected from compounds of formulae (I) and (II), enantiomers, diastereomers, racemates, tautomers, hydrates, solvates thereof, pharmaceutically acceptable salts, amides and esters thereof. The invention features methods for treating or preventing inflammation in a subject, comprising administering to the subject in connection with an inflammatory response a pharmaceutical composition that comprises a therapeutically effective amount of at least one anti-inflammatory compound selected from compounds of formulae (I) and (II), enantiomers, diastereomers, racemates, tautomers, hydrates, solvates thereof, pharmaceutically acceptable salts, amides and esters thereof. The invention also features methods for treating or preventing an H4 receptor-mediated condition in a subject, comprising administering to the subject a pharmaceutical composition that comprises a therapeutically effective amount of at least one H4 receptor modulator selected from compounds of formulae (I) and (II), enantiomers, diastereomers, racemates, tautomers, hydrates, solvates thereof, pharmaceutically acceptable salts, amides and esters thereof. In addition, the invention features methods for modulating an H4 receptor expression, comprising exposing an H4 receptor to at least one compound selected from compounds of formulae (I) and (II), enantiomers, diastereomers, racemates, tautomers, hydrates, solvates thereof, pharmaceutically acceptable salts, amides and esters thereof. Furthermore, the invention features methods for inhibiting leukocyte recruitment in a subject, comprising administering to the subject a pharmaceutical composition that comprises a therapeutically effective amount of at least one leukocyte recruitment inhibitor selected from compounds of formulae (I) and (II), enantiomers, diastereomers, racemates, tautomers, hydrates, solvates thereof, pharmaceutically acceptable salts, amides and esters thereof. Detailed Description The present invention is directed to compounds of formulae (I) or (II) as herein defined, enantiomers, diastereomers, racemates, tautomers, hydrates, solvates thereof, pharmaceutically acceptable salts, amides and esters thereof, pharmaceutical compositions that contain at least one of such compounds, methods of using, including treatment and/or prevention of conditions such as those that are mediated by the H4 receptor, and methods of making such pharmaceutical compositions. The following terms are defined below, and by their usage throughout the disclosure. "Alkyl" includes straight chain and branched hydrocarbons with at least one hydrogen removed to form a radical group. Alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, 1-methylpropyl, pentyl, isopentyl, sec-pentyl, hexyl, heptyl, octyl, and so on. Alkyl does not include cycloalkyl. "Alkenyl" includes straight chain and branched hydrocarbon radicals as above with at least one carbon-carbon double bond (sp2). Unless indicated otherwise by the prefix that indicates the number of carbon members, alkenyls include ethenyl (or vinyl), prop-1-enyl, prop-2-enyl (or allyl), isopropenyl (or 1- methylvinyl), but-1-enyl, but-2-enyl, butadienyls, pentenyls, hexa-2,4-dienyl, and so on. "Alkynyl" includes straight chain and branched hydrocarbon radicals as above with at least one carbon-carbon triple bond (sp). Unless indicated otherwise by the prefix that indicates the number of carbon members, alkynyls include ethynyl, propynyls, butynyls, and pentynyls. Hydrocarbon radicals having a mixture of double bonds and triple bonds, such as 2-penten-4-ynyl, are grouped as alkynyls herein. "Alkoxy" includes a straight chain or branched alkyl group with a terminal oxygen linking the alkyl group to the rest of the molecule. Alkoxy includes methoxy, ethoxy, propoxy, isopropoxy, butoxy, t-butoxy, pentoxy and so on. "Aminoalkyl", thioalkyl", and "sulfonylalkyl" are analogous to alkoxy, replacing the terminal oxygen atom of alkoxy with, respectively, NH (or NR), S, and SO2. Unless indicated otherwise by the prefix that indicates the number of carbon members, "cycloalkyl" includes cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, and so on. Unless indicated otherwise by the prefix that indicates the number of members in the cyclic structure, "heterocyclyl", "heterocyclic" or "heterocycle" is a 3- to 8-member aromatic, saturated, or partially saturated single or fused ring system that comprises carbon atoms wherein the heteroatoms are selected from N, O, and S. Examples of heterocyclyls include thiazoylyl, furyl, pyranyl, isobenzofuranyl, pyrrolyl, imidazolyl, pyrazolyl, isothiazolyl, isoxazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolizinyl, isoindolyl, indolyl, indazolyl, purinyl, quinolyl, furazanyl, pyrrolidinyl, pyrrolinyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, pyrazolinyl, piperidyl, piperazinyl, indolinyl, and morpholinyl. For example, preferred heterocyclyls or heterocyclic radicals include morpholinyl, piperazinyl, pyrrolidinyl, pyridyl, cyclohexylimino, cycloheptylimino, and more preferably, piperidyl. Carbocycle is a cycloalkyl or a partially saturated cycloalkyl that is not "Aryl" includes phenyl, naphthyl, biphenylyl, tetrahydronaphthyl, and so on, any of which may be optionally substituted. Aryl also includes arylalkyl groups such as benzyl, phenethyl, and phenylpropyl. Aryl includes a ring system containing an optionally substituted 6-membered carbocyclic aromatic ring, said system may be bicyclic, bridged, and/or fused. The system may include rings that are aromatic, or partially or completely saturated. Examples of ring systems include indenyl, pentalenyl, 1 -4-dihydronaphthyl, indanyl, benzimidazolyl, benzothiophenyl, indolyl, benzofuranyl, isoquinolinyl, and so on. Unless indicated otherwise, the terms "heteroaryl" or "heteroaromatic" refer to those heterocycles that are aromatic in nature. Examples illustrating heteroaryl are thienyl, furanyl, pyrrolyl, imidazolyl, oxazolyl, thiazolyl, benzothienyl, benzofuranyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, pyridyl, and pyrimidinyl. "Halo" includes fluoro, chloro, bromo, and iodo, and is preferably fluoro or chloro. When not specifically qualified, the terms "optionally substituted" used herein refer to at least one valence allowed substitution, wherein the substituent(s) is(are) independently selected from the group comprising at least: -C1-6alkyl, halo, -CF3, -OCF3, -ORc, -SRC, -S(O)Rc, -SO2Rc, C1-4alkoxy, cyano, nitro, -C(O)NRaRb, -C(O)phenyl, -C(O)C1-6alkyl, -S(O)C1-4alkyl, and -SO2C1-4alkyl. As in standard chemical nomenclature, the group phenyl is herein referred to as "phenyl" or as "Ph". To provide a more concise description, some of the quantitative expressions given herein are not qualified with the term "about". It is understood that whether the term "about" is used explicitly or not, every quantity given herein is meant to refer to the actual given value, and it is also meant to refer to the approximation to such given value that would reasonably be inferred based on the ordinary skill in the art, including equivalents and approximations due to the experimental and/or measurement conditions for such given value. Whenever a yield is given as a percentage, such yield refers to a mass of the entity for which the yield is given with respect to the maximum mass of the same entity that could be obtained under the particular stoichiometric conditions. Concentrations that are given as percentages refer to mass ratios, unless indicated differently. It is understood that substitutions and combinations of substitutions recited herein, whether stated explicitly or not, refer to substitutions that are consistent with the valency of the member being substituted. Terms such as "valence allowed site," "valence allowed member," and morphological variations thereof are used in this sense. For example, "valence allowed" when applied to a carbon member refers to the tetravalency of C; it refers to the trivalency of N when applied to a nitrogen member; and it refers to the bonding of a nitrogen member that is conventionally characterized with a positive electric charge or that is in a quaternary form. The present invention also encompasses compounds as described herein and equivalents thereof with at least one valence allowed nitrogen member, including but not limited to a quaternary nitrogen member and a nitrogen oxide, each of which may be prepared according to known methods (See, J. March, Advanced Organic Chemistry, 4th ed., 1991, pp. 411-412, 1200-1201; R.C. Larock, Comprehensive Organic Transformations, 1989, pp. 397-400, 421-425; and references cited therein). Particular preferred compounds of the invention comprise an imidazole compound of formula (I) or (II), or an enantiomer, diastereomer, racemate, tautomer, hydrate, solvate thereof, or a pharmaceutically acceptable salt, amide or ester thereof, wherein R1-12, X, Y, Z, W, and n have any of the meanings defined hereinabove and equivalents thereof, or at least one of the following assignments and equivalents thereof. Such assignments may be used where appropriate with any of the definitions, claims or embodiments defined herein: Y is CR10R11; Y is CH2; Z is N or CH; n= 1 or 2; n = 1 ; one or both of R1 and R2 are a mono- or di-substituted phenyl ring; only one of R1 or R2 is a mono-substituted phenyl ring; R3 is -H, -F, -CI, methyl, or ethyl; R3 is -F, -CI, or methyl; R3 is -CI or methyl; R4 is -H, -F, -CI, or methyl; R5 is -H, methyl, or hydroxy; R5 is H; R6 and R7 are, independently, selected from the group consisting of a)H, b) methyl, ethyl, propyl, isopropyl, and c) trifluoromethyl; R6 and R7 are, independently, -H or methyl; R8 is-H, methyl, or ethyl; R8 is methyl; and R9 is -H, -F, -CI, or methyl. Compounds of formula (I) or (II) comprise compounds that satisfy any one of the combinations of definitions given herein and equivalents thereof. It is understood that some compounds referred to herein are chiral and/or have geometric isomeric centers, for example E- and Z- isomers. The present invention encompasses all such optical isomers, including diastereoisomers and racemic mixtures, and geometric isomers that possess the activity that characterizes the compounds of this invention. In addition, certain compounds referred to herein can exist in solvated as well as unsolvated forms. It is understood that this invention encompasses all such solvated and unsolvated forms that possess the activity that characterizes the compounds of this invention. Compounds according to the present invention that have been modified to be detectable by some analytic technique are also within the scope of this invention. An example of such compounds is an isotopically labeled compound, such as an 18F isotopically labeled compound that may be used as a probe in detection and/or imaging techniques, such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT). Another example of such compounds is an isotopically labeled compound, such as a deuterium and/or tritium labeled compound that may be used in reaction kinetic studies. The present invention includes within its scope prodrugs of the compounds of this invention. In general, such prodrugs will be functional derivatives of the compounds that are readily convertible in vivo into the required compound. Thus, in the methods of treatment of the present invention, the term "administering" shall encompass the treatment of the various disorders described with the compound specifically disclosed or with a compound that may not be specifically disclosed, but that converts to the specified compound in vivo after administration to the patient. Conventional procedures for the selection and preparation of suitable prodrug derivatives are described, for example, in "Design of Prodrugs", ed. H. Bundgaard, Elsevier, 1985. Reference to a compound herein stands for a reference to any one of: (a) the actually recited form of such compound, and (b) any of the forms of such compound in the medium in which the compound is being considered when named. For example, reference herein to a compound such as R- COOH, encompasses reference to any one of, for example, R-COOH(S), R- COOH(SOl), and R-COO-(SOl). In this example, R-COOH(S) refers to the solid compound, as it could be for example in a tablet or some other solid pharmaceutical composition or preparation; R-COOH(SOl) refers to the undissociated form of the compound in a solvent, such as water; and R-COO- (SOl) refers to the dissociated form of the compound in a solvent, such as the dissociated form of the compound in an aqueous environment, whether such dissociated form derives from R-COOH, from a salt thereof, or from any other entity that yields R-COO- upon dissociation in the medium being considered. In another example, an expression such as "exposing an entity to compound of formula R-COOH" refers to the exposure of such entity to the form, or forms, of the compound R-COOH that exists, or exist, in the medium in which such exposure takes place. In this regard, if such entity is for example in an aqueous environment, it is understood that the compound R-COOH is in such same medium, and therefore the entity is being exposed to species such as R- COOH(aq) and/or R-COO-(aq), where the subscript "(aq)" stands for "aqueous" according to its conventional meaning in chemistry and biochemistry. A carboxylic acid functional group has been chosen in these nomenclature examples; this choice is not intended, however, as a limitation but it is merely an illustration. It is understood that analogous examples can be provided in terms of other functional groups, including but not limited to hydroxyl, basic nitrogen members, such as those in amines, and any other group that interacts or transforms according to known manners in the medium that contains the compound. Such interactions and transformations include, but are not limited to, dissociation, association, tautomerism, solvolysis, including hydrolysis, solvation, including hydration, protonation, and deprotonation. No further examples in this regard are provided herein because these interactions and transformations in a given medium are known by any one of ordinary skill in the art. Embodiments of this invention were made according to the synthetic methods outlined in Schemes 1 and 2 and are selected from: EX Compound 1 1 -(3-{4-[4,5-Bis-(4-bromo-phenyl)-1H-imidazol-2-yl]-3-chloro- phenoxy}-propyl)-4-methyl-piperazine; 2 1 -{3-[3-Chloro-4-(4,5-diphenyl-1H-imidazol-2-yl)-phenoxy]- propyl}-4-methyl-piperazine; 3 1 -(3-{4-[4,5-Bis-(2-chloro-phenyl)-1H-imidazol-2-yl]-3-chloro- phenoxy}-propyl)-4-methyl-piperazine; 4 1 -(3-{4-(4,5-Bis-(4-methoxy-phenyl)-1H-imidazol-2-yl]-3-chloro- phenoxy}-propyl)-4-methyl-piperazine; 5 1 -{3-[3-Chloro-4-(4,5-di-p-tolyl-1H-imidazol-2-yl)-phenoxy]- propyl}-4-methyl-piperazine; 6 1 -(3-{4-[4,5-Bis-(4-fluoro-phenyl)-1H-imidazol-2-yl]-3-chloro- phenoxy}-propyl)-4-methyl-piperazine; 7 1-(3-{4-[4,5-Bis-(3-methoxy-phenyl)-1H-imidazol-2-yl]-3-chloro- phenoxy}-propyl)-4-methyl-piperazine; 8 1-(3-{4-[4,5-Bis-(3-methoxy-phenyl)-1H-imidazol-2-yl]-2-fluoro- phenoxy}-propyl)-4-methyl-piperazine; 9 1 -(3-{4-[4,5-Bis-(4-bromo-phenyl)-1H-imidazol-2-yl]-3-chloro- phenoxy}-propyl)-4-methyl-[1,4]diazepane; 10 1 -(3-{4-[4,5-Bis-(3-methoxy-phenyl)-1H-imidazol-2-yl]-3-chloro- phenoxy}-propyl)-4-methyl-[1,4]diazepane 11 1 -{3-[2-Chloro-4-(5-methyl-4-phenyl-1H-imidazol-2-yl)-phenoxy]- propyl}-4-methyl-[1,4]diazepane; 12 2-{3-Chloro-4-[3-(4-methyl-[1,4]diazepan-1-yl)-propoxy]-phenyl}- 4,5,6,7-tetrahydro-1H-benzoimidazole; 13 2-{2-Chloro-4-[3-(4-methyl-[1,4]diazepan-1-yl)-propoxy]-phenyl}- 4,5,6,7-tetrahydro-1H-benzoimidazole; 14 1 -Methyl-4-{3-[3-methyl-4-(4-phenyl-5-trif luoromethyl-1H- imidazol-2-yl)-phenoxy]-propyl}-piperidine; 15 4-{3-[3-Chloro-4-(4-phenyl-5-trif luoromethyl-1H-imidazol-2-yl)- phenoxy]-propyl}-1-methyl-piperidine; 16 4-(3-{3-Chloro-4-[5-methyl-4-(3-trifluoromethyl-phenyl)-1H- imidazol-2-yl]-phenoxy}-propyl)-1-methyl-piperidine; 17 4-(3-{3-Chloro-4-[4-(3,5-dichloro-phenyl)-5-methyl-1 H-imidazol-2- yl]-phenoxy}-propyl)-1-methyl-piperidine; 18 4-(3-{4-[4-(3,5-Dichloro-phenyl)-5-methyl-1H-imidazol-2-yl]-3- methyl-phenoxy}-propyl)-1 -methyl-piperidine; 19 4-(3-{3-Chloro-4-[4-(4-chloro-phenyl)-5-methyl-1H-imidazol-2-yl]- phenoxy}-propyl)-1-methyl-piperidine; 20 4-(3-{4-[4,5-Bis-(4-fluoro-phenyl)-1H-imidazol-2-yl]-3-chloro- phenoxy}-propyl)-1-methyl-piperidine; 21 4-(3-{4-[4,5-Bis-(3-methoxy-phenyl)-1H-imidazol-2-yl]-3-chloro- phenoxy}-propyl)-1-methyl-piperidine; 22 4-(3-{3-Chloro-4-[4-(4-chloro-phenyl)-5-p-tolyl-1 H-imidazol-2-yl]- phenoxy}-propyl)-1-methyl-piperidine; 23 2-{2-Chloro-4-[3-(1-methyl-piperidin-4-yl)-propoxy]-phenyl}- 4,5,6,7-tetrahydro-1H-benzoimidazole; 24 4-{3-[3-Chloro-4-(4-methyl-5-propyl-1H-imidazol-2-yl)-phenoxy]- propyl}-1-methyl-piperidine; 25 4-{3-[3-Chloro-4-(5-ethyl-4-methyl-1 H-imidazol-2-yl)-phenoxy]- propyl}-1 -methylpiperidine; 26 1-Methyl-4-(2-{3-methyl-4-[5-methyl-4-(3-trifluoromethyl-phenyl)- 1H-imidazol-2-yl]-phenoxy}-ethoxy)-piperidine; 27 5-[4-(3,5-Dichloro-phenyl)-5-methyl-1 H-imidazol-2-yl]-2-[3-(1 - methyl-piperidin-4-yl)-propoxy]-pyridine; 28 5-[4-(4-Chloro-phenyl)-5-methyl-1H-imidazol-2-yl]-2-[3-(1 -methyl- piperidin-4-yl)-propoxy]-pyridine; 29 2-[3-(1 -Methyl-piperidin-4-yl)-propoxy]-5-[5-methyl-4-(3- trifluoromethyl-phenyl)-1H-imidazol-2-yl]-pyridine; 30 2-[3-(1 -Methyl-piperidin-4-yl)-propoxy]-5-[5-methyl-4-(4- trifluoromethyl-phenyl)-1H-imidazol-2-yl]-pyridine; 31 2-[3-(1 -Methyl-piperidin-4-yl)-propoxy]-5-(4-phenyl-5- trifluoromethyl-1H-imidazol-2-yl)-pyridine; 32 1 -Methyl-4-(3-{5-[5-methyl-4-(4-trifluoromethyl-phenyl)-1H- imidazol-2-yl]-pyridin-2-yloxy}-propyl)-piperazine; 33 1 -Methyl-4-(3-{5-[5-methyl-4-(3-trifluoromethyl-phenyl)-1 H- imidazol-2-yl]-pyridin-2-y!oxy}-propyl)-piperazine; 34 4-(4-{3-[4-(4-Chloro-phenyl)-5-methyl-1H-imidazol-2-yl]-phenoxy}- butyl)-1-methyl-piperidine; 35 1 -Methyl-4-{4-[3-(4-phenyl-5-trifluoromethyl-1 H-imidazol-2-yl)- phenoxy]-butyl}-piperidine; 36 2-[4-(1 -Methyl-piperidin-4-yl)-butoxy]-4-(4-phenyl-5- trifluoromethyl-1H-imidazol-2-yl)-pyridine; 37 2-[4-(1 -Methyl-piperidin-4-yl)-butoxy]-4-[5-methyl-4-(3- trifluoromethyl-phenyl)-1H-imidazol-2-yl]-pyridine; 38 4-{3-[4-(5-lsobutyl-4-methyl-1H-imidazol-2-yl)-3-methyl-phenoxy]- propyl}-1 -methyl-piperidine; 39 4-[4-(4-Chloro-phenyl)-5-methyl-1 H-imidazol-2-yl]-2-[4-(1 -methyl- piperidin-4-yl)-butoxy]-pyridine; 40 4-{3-[3-Chloro-4-(5-isobutyl-4-methyl-1H-imidazol-2-yl)-phenoxy]- propyl}-1 -methyl-'piperidine; 41 1 -Methyl-4-(4-{3-[5-methyl-4-(4-trifluoromethyl-phenyl)-1H- imidazol-2-yl]-phenoxy}-butyl)-piperidine; 42 1 -{3-[2-Chloro-4-(1 H-imidazol-2-yl)-phenoxy]-propyl}-4-methyl- piperazine; 43 1 -{3-[3-Chloro-4-(4,5-dimethyl-1H-imidazol-2-yl)-phenoxy]- propyl}-4-methyl-piperazine; 44 1 -{3-[3-Chloro-4-(4-phenyl-5-trifluoromethyl-1H-imidazol-2-yl)- phenoxy]-propyl}-4-methyl-piperazine; 45 1 -{3-[2-Chloro-4-(4-phenyl-5-trifluoromethyl-1H-imidazol-2-yl)- phenoxy]-propyl}-4-methyl-[1,4]diazepane; 46 1-Methyl-4-(3-{3-methyl-4-[5-methyl-4-(3-trifluoromethy!-phenyl)- 1H-imidazol-2-yl]-phenoxy}-propyl)-piperidine; 47 4-(3-{4-[4-(4-Chloro-phenyl)-5-methyl-1H-innidazol-2-yl]-3-methyl- phenoxy}-propyl)-1-methyl-piperidine; 48 4-(2-{4-[4-(4-Chloro-phenyl)-5-methyl-1H-imidazol-2-yl]-3-methyl- phenoxy}-ethoxy)-1-methyl-piperidine; 49 1 -(3-{4-[4-(4-Chloro-phenyl)-5-methyl-1 H-imidazol-2-yl]-3-methyl- phenoxy}-2-methyl-propyl)-4-methyl-piperazine; 50 2-[4-(4-Chloro-phenyl)-5-methyl-1 H-imidazol-2-yl]-6-[4-(1 -methyl- piperidin-4-yl)-butoxy]-pyridine; 51 4-Methyl-2-[3-(1-methyl-piperidin-4-yl)-propoxy]-5-[5-methyl-4-(3- trifluoromethyl-phenyl)-1 H-imidazol-2-yl]-pyridine; 52 5-Bromo-4-[4-(4-chloro-phenyl)-5-methyl-1H-imidazol-2-yl]-2-[4- (1 -methyl-piperidin-4-yl)-butoxy]-pyridine; 53 2,4-Dimethyl-1 -{3-[4-(4-phenyl-5-trifluoromethyl-1 H-imidazol-2- yl)-phenoxy]-propyl}-piperazine; 54 1,2-Dimethyl-4-{3-[4-(4-phenyl-5-trifluoromethyl-1 H-imidazol-2- yl)-phenoxy]-propyl}-piperazine; 55 3-Chloro-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-4-(4-phenyl-5- trifluoromethyl-1H-imidazol-2-yl)-pyridine; 56 1 -Methyl-4-(4-{4-[5-methyl-4-(3-trifluoromethyl-phenyl)-1H- imidazol-2-yl]-pyridin-2-yloxy}-butyl)-[1,4]diazepane; 57 5-Bromo-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-4-[5-methyl-4-(3- trifluoromethyl-phenyl)-1H-imidazol-2-yl]-pyridine; 58 4-[4-(4-Chloro-phenyl)-5-trifluoromethyl-1 H-imidazol-2-yl]-2-[4-( 1 - methyl-piperidin-4-yl)-butoxy]-pyrimidine; 59 4-(3-{4-[5-Cyclopropylmethyl-4-(3-trifluoromethyl-phenyl)-1H- imidazol-2-yl]-3-methyl-phenoxy}-propyl)-1-methyl-piperidine; 60 1 -{4-[4-(4-Chloro-phenyl)-5-methyI-1H-imidazol-2-yl]-3-methyl- phenoxy}-3-(4-methyl-piperazin-1-yl)-propan-2-ol; 61 4-(3-{3-Chloro-4-[4-(4-chloro-phenyl)-5-methyl-1H-imidazol-2-yl]- phenoxy}-propyl)-piperidine; 62 4-(3-{3-Chloro-4-[4-(4-chloro-phenyl)-5-methyl-1H-imidazol-2-yl]- phenoxy}-propyl)-1-ethyl-piperidine; 63 4-(3-{3-Chloro-4-[4-(4-chloro-phenyl)-5-methyl-1H-imidazol-2-yl]- phenoxy}-propyl)-1-isopropyl-piperidine; 64 1 -Methyl-4-{3-[4-(4-phenyl-5-trifluoromethyl-1 H-imidazol-2-yl)- naphthalen-1-yloxy]-propyl}-piperidine; 65 1 -(4-Methyl-piperazin-1 -yl)-3-{5-[5-methyl-4-(4-trifluoromethyl- phenyl)-1H-imidazol-2-yl]-pyridin-2-yloxy}-propan-1-one; 66 6-[4-(4-Chloro-phenyl)-5-methyl-1H-imidazol-2-yl]-3-fluoro-2-[4- (1-methyl-piperidin-4-yl)-butoxy]-pyridine; 67 1-Methyl-4-(4-{3-methyl-6-[5-methyl-4-(3-trifluoromethyl-phenyl)- 1H-imidazol-2-yl]-pyridin-2-yloxy}-butyt)-piperazine; 68 1-Methyl-4-{3-[4-(5-methyl-4-thiophen-2-yl-1H-imidazol-2-yl)- phenoxy]-propyl}-piperidine; and 69 2-{3-[4-(1-Methyl-piperidin-4-yl)-butoxy]-phenyl}-3H-imidazo[4,5- b]pyridine. Compounds according to the present invention may be made according tc processes within the skill of the art and/or according to processes of this invention, such as those described in the schemes and examples that follow and by matrix or combinatorial methods. To obtain the various compounds herein, starting materials may be employed that carry the ultimately desired substituents though the reaction scheme with or without protection as appropriate. Starting materials may be obtained from commercial sources or synthesized by methods known to one skilled in the art. Alternatively, it may be necessary to employ, in the place of the ultimately desired substituent, a suitable group, which may be carried through the reaction scheme and replaced as appropriate with the desired substituent. Those of ordinary skill in the art will be able to modify and adapt the guidance provided herein to make compounds according to the present invention. Embodiments of processes illustrated herein include, when chemically meaningful, one or more steps such as hydrolysis, halogenation, protection, and deprotection. These steps can be implemented in light of the teachings provided herein and the ordinary skill in the art. During any of the processes for preparation of the compounds of the present invention, it may be necessary and/or desirable to protect sensitive or reactive groups on any of the molecules concerned. In addition, compounds of this invention may be modified by using protecting groups; such compounds, precursors, or prodrugs are also within the scope of the invention. This modification may be achieved by means of conventional protecting groups, such as those described in "Protective Groups in Organic Chemistry", ed. J.F.W. McOmie, Plenum Press, 1973; and T.W. Greene & P.G.M. Wuts, "Protective Groups in Organic Synthesis", 3rd ed., John Wiley & Sons, 1999. The protecting groups may be removed at a convenient subsequent stage using methods known from the art. Referring to Schemes 1 and 2, there are disclosed the following notes and additions. The starting materials for the steps described below regarding Schemes 1 and 2 are commercially available or easily accessible to those skilled in the art. Compounds of formula (I) or (II) are prepared by condensing a suitably substituted 1,2-diketone (III) with a suitably substituted aldehyde (IV') or (IV") in the presence of a source of ammonia (NH3) to form a compound of formula (I) when the aldehyde (IV') has a para ether substitution with respect to the aldehyde group (Scheme 1), or a compound of formula (II) when the aldehyde (IV") has a meta ether substitution with respect to the aldehyde group (Scheme 2). Suitable sources of ammonia include liquid and gaseous ammonia, aqueous ammonia, ammonia in methyl or ethyl alcohol, ammonia in 1,4- dioxane, NH4OAc, NH4CI, NH4HCO3, (NH4)2CO3, ammonium benzoate, and other chemically compatible sources of ammonia or ammonium salts, and mixtures thereof. This condensation is preferably performed in a heated medium in a chemically compatible solvent. Reaction medium temperatures range preferably from about room temperature to about 110 °C, more preferably from about 50 °C to about 80 °C. Solvents that can be used for this reaction include ethanol, isopropanol, acetic acid, water, THF, dioxane, DMF, DMA, and DMSO, preferably methanol, and mixtures thereof. Suitably substituted aryl or heteroaryl aldehydes (IV') and (IV") can be prepared according to procedures known in the art. In one preparation procedure, a suitably substituted hydroxy benzaldehyde is reacted with a suitably substituted moiety to form the ether link in compounds (IV') and (IV"). Reaction with a suitably substituted 4-hydroxy benzaldehyde leads to the formation of compound (IV'), and reaction with a suitably substituted 3-hydroxy benzaldehyde leads to the formation of compound (IV"). Where the processes for the preparation of the compounds according to the invention give rise to mixture of stereoisomers, these isomers may be separated by conventional techniques such as resolution, for example by formation of diastereomeric salts, kinetic resolution including variants thereof, such as dynamic resolution, preferential crystallization, biotransformation, enzymatic transformation, and preparative chromatography. The compounds may be prepared in racemic form, or individual enantiomers may be prepared either by enantiospecific synthesis or by resolution. The compounds may, for example, be resolved into their component enantiomers by standard techniques, such as the formation of diastereomeric pairs by salt formation with an optically active acid, such as (-)-di-p-toluoyl-D-tartaric acid and/or (+)-di-p- toluoyl-L-tartaric acid followed by fractional crystallization and regeneration of the free base. The compounds may also be resolved by formation of diastereomeric esters or amides, followed by chromatographic separation and removal of the chiral auxiliary. Alternatively, the compounds may be separated using a chiral HPLC column. Regioisomeric mixtures may also be separated into their constituent regioisomers by conventional techniques. For therapeutic use, salts of the compounds of the present invention are those that are pharmaceutically acceptable. However, salts of acids and bases that are non-pharmaceutically acceptable may also find use, for example, in the preparation or purification of a pharmaceutically acceptable compound. All salts, whether pharmaceutically acceptable or not are included within the ambit of the present invention. Pharmaceutically acceptable salts, esters, and amides of compounds according to the present invention refer to those salts, amides and ester forms of the compounds of the present invention that would be apparent to the pharmaceutical chemist, i.e., those that are non-toxic and that would favorably affect the pharmacological properties of said compounds of the present invention. Those compounds having favorable pharmacological properties would be apparent to the pharmaceutical chemist, i.e., those that are non-toxic and that possess such pharmacological properties to provide sufficient palatability, absorption, distribution, metabolism and excretion. Other factors, more practical in nature, that are also important in the selection are cost of raw materials, ease of crystallization, yield, stability, hygroscopicity, and flowability of the resulting bulk drug. Examples of acids that may be used in the preparation of pharmaceutically acceptable salts include the following: acetic acid, 2,2- dichloroacetic acid, acylated amino acids, adipic acid, alginic acid, ascorbic acid, L-aspartic acid, benzenesulfonic acid, benzoic acid, 4-acetamidobenzoic acid, (+)-camphoric acid, camphorsulfonic acid, (+)-(1S)-camphor-10-sulfonic acid, capric acid, caproic acid, caprylic acid, cinnamic acid, citric acid, cyclamic acid, cyclohexanesulfamic acid, dodecylsulfuric acid, ethane-1,2-disulfonic acid, ethanesulfonic acid, 2-hydroxy-ethanesulfonic acid, formic acid, fumaric acid, galactaric acid, gentisic acid, glucoheptonic acid, D-gluconic acid, D- glucuronic acid, L-glutamic acid, a-oxo-glutaric acid, glycolic acid, hippuric acid, hydrobromic acid, hydrochloric acid, hydroiodic acid, (+)-L-lactic acid, (±)-DL- lactic acid, lactobionic acid, maleic acid, (-)-L-malic acid, malonic acid, (±)-DL- mandelic acid, methanesulfonic acid, naphthalene-2-sulfonic acid, naphthalene-1,5-disulfonic acid, 1-hydroxy-2-naphthoic acid, nicotinic acid, nitric acid, oleic acid, orotic acid, oxalic acid, palmitic acid, pamoic acid, perchloric acid, phosphoric acid, L-pyroglutamic acid, saccharic acid, salicylic acid, 4-amino-salicylic acid, sebacic acid, stearic acid, succinic acid, sulfuric acid, tannic acid, (+)-L-tartaric acid, thiocyanic acid, p-toluenesulfonic acid and undecylenic acid. Compounds of the present invention containing acidic protons may be converted into their therapeutically active non-toxic metal or amine addition salt forms by treatment with appropriate organic and inorganic bases. Appropriate base salt forms comprise, for example, the ammonium salts; the alkali and earth alkaline metal salts (e.g. lithium, sodium, potassium, magnesium, calcium salts, which may be prepared by treatment with, for example, magnesium hydroxide, calcium hydroxide, potassium hydroxide, zinc hydroxide, or sodium hydroxide); and amine salts made with organic bases (e.g. primary, secondary and tertiary aliphatic and aromatic amines such as L-arginine, benethamine, benzathine, choline, deanol, diethanolamine, diethylamine, dimethylamine, dipropylamine, diisopropylamine, 2-(diethylamino)-ethanol, ethanolamine, ethylamine, ethylenediamine, isopropylamine, N-methyl-glucamine, hydrabamine, 1H-imidazole, L-lysine, morpholine, 4-(2-hydroxyethyl)- morpholine, methylamine, piperidine, piperazine, propylamine, pyrrolidine, 1-(2- hydroxyethyl)-pyrrolidine, pyridine, quinuclidine, quinoline, isoquinoline, secondary amines, triethanolamine, trimethylamine, triethylamine, N-methyl-D- glucamine, 2-amino-2-(hydroxymethyl)-1,3-propanedioi, and tromethamine). See, e.g., S.M. Berge, et al., "Pharmaceutical Salts", J. Pharm. Sci., 1977, 66:1-19, which is incorporated herein by reference. "Salt" also comprises the hydrates and solvent addition forms that compounds of the present invention are able to form. Examples of such forms are hydrates, alcoholates, and generally solvates. Examples of suitable esters include C1-7alkyl, C5-7cycloalkyl, phenyl, substituted phenyl, and phenylC1-6alkyl- esters. Preferred esters include methyl esters. Furthermore, examples of suitable esters include such esters where one or more carboxyl substituents is replaced with p-methoxybenzyloxy- carbonyl, 2,4,6-trimethylbenzyloxycarbonyl, 9-anthryloxycarbonyl, CH3SCH2COO-, tetrahydrofur-2-yloxycarbonyl, tetrahydropyran-2-yloxy- carbonyl, fur-2-yloxycarbonyl, benzoylmethoxycarbonyl, p-nitrobenzyloxy- carbonyl, 4-pyridylmethoxycarbonyl, 2,2,2-trichloroethoxycarbonyl, 2,2,2-tribromoethoxycarbonyl, t-butyloxycarbonyl, t-amyloxycarbonyl, diphenylmethoxycarbonyl, triphenylmethoxycarbonyi, adamantyloxycarbonyl, 2-benzyloxyphenyloxycarbonyl, 4-methylthiophenyloxycarbonyl, or tetrahydropyran-2-yloxycarbonyl. Whether referred to herein explicitly or not, each of the terms "pharmaceutically acceptable salts," "pharmaceutically acceptable esters," and "pharmaceutically acceptable amides" include those salts, esters and amides, respectively that do not change the intrinsic properties of the active ingredient. See, for example, Remington, The Science and Practice of Pharmacy, 704 (20th ed., 2000). "Patient" or "subject" includes mammals such as human beings and animals (e.g., dogs, cats, horses, rats, rabbits, mice, non-human primates) in need of observation, experiment, treatment or prevention in connection with the relevant disease or condition. Preferably, the patient is a human being. "Composition" includes a product comprising the specified ingredients in the specified amounts, including in the effective amounts, as well as any product that results directly or indirectly from combinations of the specified ingredients in the specified amounts. Administration of at least one compound of formulae (I) and (II) and/or derivative thereof refers to the administration of such compound in a suitable administration form, whether as such compound itself or as part of a suitable pharmaceutical composition. "Therapeutically effective amount" or "effective amount" and grammatically related terms mean that amount of active compound or pharmaceutical agent that elicits the biological or medicinal response in an in vitro system, a tissue system, an animal or human being, that is being sought by a researcher, veterinarian, medical doctor, or other clinician, where the medicinal response includes, but is not limited to, alleviation of the symptoms of the disease or disorder being treated. Analogously, terms such as "inhibitory amount", "anti-inflammatory amount," "prophylactically effective amount" and grammatically related terms refer to the amount of active compound or pharmaceutical agent that elicits the response being referred to, such as inhibition and anti-inflammatory effect, respectively, in the system being studied, whether an in vitro system, an animal or a human being that is sought by a researcher, veterinarian, medical doctor, or other clinician, where the medicinal response includes, but is not limited to, alleviation of the symptoms of the disease or disorder being treated. As used herein, "treating" a disorder, and grammatically related terms, mean eliminating or otherwise ameliorating the cause and/or effects thereof. Terms such as to "inhibit", and grammatically related terms, the onset of a disorder or event, and to "prevent" a disorder or condition, and grammatically related terms, mean preventing, delaying or reducing the likelihood of such onset. The terms "unit dose" and their grammatical equivalent forms are used herein to refer to physically discrete units suitable as unitary dosages for human patients and other animals, each unit containing a predetermined effective, pharmacologic amount of the active ingredient calculated to produce the desired pharmacological effect. The specifications for the novel unit dosage forms of this invention are determined by, and are directly dependent on, the characteristics of the active ingredient, and on the limitations inherent in the art of compounding such an active ingredient for therapeutic use in humans and other animals. Embodiments of pharmaceutical compositions for treating or preventing an H4 receptor-mediated condition in a subject that comprise a therapeutically effective amount of at least one H4 receptor modulator selected from compounds of formulae (I) and (II), enantiomers, diastereomers, racemates, tautomers, hydrates, solvates thereof, pharmaceutically acceptable salts, amides and esters thereof, further comprise a pharmaceutically acceptable carrier. Embodiments of pharmaceutical compositions for inhibiting leukocyte recruitment in a subject that comprise a therapeutically effective amount of at least one leukocyte recruitment inhibitor selected from compounds of formulae (I) and (II), enantiomers, diastereomers, racemates, tautomers, hydrates, solvates thereof, pharmaceutically acceptable salts, amides and esters thereof, further comprise a pharmaceutically acceptable carrier. Embodiments of anti-inflammatory compositions that comprise a therapeutically effective amount of at least one anti-inflammatory compound selected from compounds of formulae (I) and (II), enantiomers, diastereomers, racemates, tautomers, hydrates, solvates thereof, pharmaceutically acceptable salts, amides and esters thereof, further comprise a pharmaceutically acceptable carrier. Embodiments of methods for treating or preventing inflammation in a subject that comprise administering to the subject in connection with an inflammatory response a pharmaceutical composition comprising a therapeutically effective amount of at least one anti-inflammatory compound selected from compounds of formulae (I) and (II), enantiomers, diastereomers, racemates, tautomers, hydrates, solvates thereof, pharmaceutically acceptable salts, amides and esters thereof, include methods wherein said inflammatory response is a response to at least one of the conditions: inflammatory disorders, allergic disorders, dermatological disorders, autoimmune disease, lymphatic disorders, itchy skin, and immunodeficiency disorders. Embodiments of methods for treating or preventing inflammation in a subject that comprise administering to the subject in connection with an inflammatory response a pharmaceutical composition comprising a therapeutically effective amount of at least one anti-inflammatory compound selected from compounds of formulae (I) and (II), enantiomers, diastereomers, racemates, tautomers, hydrates, solvates thereof, pharmaceutically acceptable salts, amides and esters thereof, include methods wherein said inflammatory response is a response to chemotherapy. Embodiments of methods for treating or preventing inflammation in a subject that comprise administering to the subject in connection with an inflammatory response a pharmaceutical composition comprising a therapeutically effective amount of at least one anti-inflammatory compound selected from compounds of formulae (I) and (II), enantiomers, diastereomers, racemates, tautomers, hydrates, solvates thereof, pharmaceutically acceptable salts, amides and esters thereof, include methods wherein at least one of the following is satisfied: said inflammatory response is a response to a physical stimulus; said inflammatory response is a response to a chemical stimulus; said inflammatory response is a response to infection; said inflammatory response is a response to an invasion by a body that is foreign to said subject; said inflammatory response is a response to an immunological stimulus; said inflammatory response is a response to a non-immunological stimulus; said inflammatory response is a response to at least one of the conditions: Allergy, asthma, chronic obstructed pulmonary disease (COPD), atherosclerosis, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, and more specifically wherein said inflammatory bowel disease is at least one of Crohn's disease and ulcerative colitis, psoriasis, allergic rhinitis, scleroderma, autoimmune thyroid disease, immune-mediated diabetes mellitus, and lupus; said inflammatory response is a response to at least one of the conditions: Myasthenia gravis, autoimmune neuropathy, and more specifically wherein said autoimmune neuropathy is Guillain-Barre neuropathy, autoimmune uveitis, autoimmune hemolytic anemia, pernicious anemia, autoimmune thrombocytopenia, temporal arteritis, anti-phospholipid syndrome, vasculitides, and more specifically wherein said vasculitides is Wegener's granulomatosis, Behcet's disease, dermatitis herpetiformis, pemphigus vulgaris, vitiligio, primary biliary cirrhosis, autoimmune hepatitis, autoimmune oophoritis, autoimmune WE CLAIM: 1. A compound of formula (II): wherein W is, independently from other member and substituent assignments, N; X is, independently from other member and substituent assignments, CR9; Y is, independently from other member and substituent assignments, O, NR10, or CR10R11; Z is, independently from other member and substituent assignments, N or CR12; n is, independently from other member and substituent assignments, 0, 1, or 2; each of R1-2 is, independently from other member and substituent assignments, - H, -CF3, -C1-6alkyl, -C3-6cycloalkyl, optionally substituted aryl or optionally substituted heteroaryl; or, R1 and R2 taken together with the carbon atoms to which they are attached form a cyclic structure Cyc1 selected from 5- membered carbocycle, and 5- or 6-membered heterocycle with 1 heteroatom, wherein said cyclic structure Cyc1 is, independently from other substituent assignments, substituted with 0, 1, or 2 substituents selected from -C1-3alkyl, halo, hydroxy, amino, and -C1-3alkoxy; each of R3-4 and R9 is, independently from other member and substituent assignments, -H, -C1-6alkyl, halo, -CF3, -OCF3, -ORc, -SRc, -S(O)Rc, -SO2Rc, C1-4alkoxy, cyano, nitro, -C(O)NRaRb, -C(O)phenyl, -C(O)C1-6alkyl, -S(O)C1- 4alkyl, or -SO2C1-4alkyl; or, R3 and R4 taken together with the carbon atoms to which they are attached form a cyclic structure Cyc2 selected from aryl, 5- or 6- membered carbocycle, and 5- or 6-membered heterocycle with 1 or 2 heteroatoms, wherein said cyclic structure Cyc2 is, independently from other substituent assignments, substituted with 0, 1, or 2 substituents selected from -C1-3alkyl, halo, hydroxy, amino, and -C1-3alkoxy; wherein each of Ra, Rb and Rc is, independently from other substituent assignments, selected from H, C1-4alkyl, C3-6cycloalkyl, phenyl, (C3-6cycloalkyl)C1-2alkyl-, benzyl and phenethyl, or Ra and Rb taken together with the nitrogen to which they are attached, form a 4-7 membered heterocyclic ring HetCyc1, wherein said ring HetCyc1 has 0 or 1 additional heteroatoms selected from O, S, >NH and >NC1-6alkyl, and wherein any phenyl, phenethyl, benzyl, alkyl or cycloalkyl moiety in any of said R1-4 , Ra, Rb, Rc, and said ring HetCyc1 is optionally, and independently from other substituent assignments, substituted with 1, 2 or 3 substituents selected from C1-3alkyl, halo, hydroxy, amino, and C1-3alkoxy; R5 is, independently from other member and substituent assignments, -H, -C1-6alkyl, -C1-4alkoxy, or hydroxy; each of R6 and R7 is, independently from other member and substituent assignments, -H or -C1-6alkyl, or R6 and R7 taken together form a 5-6 membered cyclic structure Cyc3, wherein said cyclic structure Cyc3 is a 5- or 6-membered carbocycle or a 5- or 6-membered heterocycle with 1 or 2 heteroatoms, and wherein said cyclic structure Cyc3 is, independently from other substituent assignments, substituted with 0, 1, or 2 substituents selected from -C1-3alkyl, halo, hydroxy, amino, and -C1-3alkoxy; R8 is, independently from other member and substituent assignments, -H or -C1-4alkyl; each of R10 and R11 is, independently from other member and substituent assignments, -H or -C1-4alkyl; or, when Y is CR10R11, R10 and R11 taken together with the carbon member to which they are attached form an optionally substituted cyclic structure Cyc4, wherein said cyclic structure Cyc4 is a 3- to 6-membered carbocycle or a 3- to 6-membered non-aromatic heterocycle with 0 or 1 additional heteroatoms, or CR10R11 is C=O; R12 is, independently from other member and substituent assignments, -H, -C1-4alkyl, hydroxy, or -C1-4alkoxy; an enantiomer, diastereomer, racemate, tautomer, hydrate or solvate thereof, or a pharmaceutically acceptable salt, thereof; wherein the term "optionally substituted", when not specifically qualified, refers to one or more substituents selected from -C1-6 alkyl, halo, -CF3, -OCF3, -ORc, -SRC, -S(O)Rc, -SO2Rc, -C1- 4alkoxy, cyano, nitro, -C(o)NRaRb, -C(o)phenyl, -C(o)C1-6alkyl, -S(O)C1-4alkyl, and -SO2C1-4alkyl; with the following provisos: when Y is O or NR10, then Z is CR12 and R5 is not hydroxy or -C1-4alkoxy; when Z is N, Y is CR10R11; when R1 and R2 are both -H, Y is CH2, and R8 is methyl, then R5 is not hydroxy. 2. The compound of claim 1, wherein Y is CR10R11. 3. The compound of claim 1, wherein Y is CH2. 4. The compound of claim 1, wherein Z is N or CH. 5. The compound of claim 1, wherein n=1 or 2. 6. The compound of claim 1, wherein n=1. 7. The compound of claim 1, wherein one or both of R1 and R2 are a mono- or di- substituted phenyl ring. 8. The compound of claim 1, wherein only one of R1 or R2 is a mono-substituted phenyl ring. 9. The compound of claim 1, wherein R3 is -H, -F, -CI, methyl, or ethyl. 10. The compound of claim 1, wherein R3 is -F, -CI, or methyl. 11. The compound of claim 1, wherein R3 is -CI or methyl. 12. The compound of claim 1, wherein R4 is -H, -F, -CI, or methyl. 13. The compound of claim 1, wherein R5 is -H, methyl, or hydroxy. 14. The compound of claim 1, wherein R5 is -H. 15. The compound of claim 1, wherein R6 and R7 are, independently, selected from the group consisting of a)-H, b) methyl, ethyl, propyl, isopropyl, and c) trifluoromethyl. 16. The compound of claim 1, wherein R6 and R7 are, independently, -H or methyl. 17. The compound of claim 1, wherein R8 is -H, methyl, or ethyl. 18. The compound of claim 1, wherein R8 is methyl. 19. The compound of claim 1, wherein R9 is -H, -F, -CI, or methyl. 20. A compound selected from: 2-[4-(1-Methyl-piperidin-4-yl)-butoxy]-4-(4-phenyl-5-trifluoromethyl-1H- imidazol-2-yl)-pyridine; 2-[4-(1-Methyl-piperidin-4-yl)-butoxy]-4-[5-methyl-4-(3-trifluoromethyl-phenyl)- 1H-imidazol-2-yl]-pyridine; 4-[4-(4-Chloro-phenyl)-5-methyl-1H-imidazol-2-yl]-2-[4-(1-methyl-piperidin-4- yl)-butoxy]-pyridine; 5-Bromo-4-[4-(4-chloro-phenyl)-5-methyl-1H-imidazol-2-yl]-2-[4-(1-methyl- piperidin-4-yl)-butoxy]-pyridine; 3-Chloro-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-4-(4-phenyl-5-trifluoromethyl- 1H-imidazol-2-yl)-pyridine; 1-Methyl-4-(4-{4-[5-methyl-4-(3-trifluoromethyl-phenyl)-1H-imidazol-2-yl]- pyridin-2-yloxy}-butyl)-[1,4]diazepane; and 5-Bromo-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-4-[5-methyl-4-(3- trifluoromethyl-phenyl)-1H-imidazol-2-yl]-pyridine; 21. A pharmaceutical composition, comprising a compound as claimed in claim 1 and a pharmaceutically acceptable carrier. ABSTRACT Title: IMIDAZOLE COMPOUNDS Imidazole compounds, compositions, and methods of using them in leukocyte recruitment inhibition, in modulation H4 receptor expression, and in treating conditions such as inflammation, H4 receptor-mediated conditions, and related conditions.

Documents:

03094-kolnp-2006 abstract.pdf

03094-kolnp-2006 claims.pdf

03094-kolnp-2006 correspondence others.pdf

03094-kolnp-2006 description(complete).pdf

03094-kolnp-2006 form-1.pdf

03094-kolnp-2006 form-2.pdf

03094-kolnp-2006 form-26.pdf

03094-kolnp-2006 form-3.pdf

03094-kolnp-2006 form-5.pdf

03094-kolnp-2006 international publication.pdf

03094-kolnp-2006 international search authority report.pdf

03094-kolnp-2006 pct request.pdf

03094-kolnp-2006-correspondence others-1.1.pdf

03094-kolnp-2006-priority document.pdf

3094-KOLNP-2006-AMANDED CLAIMS.pdf

3094-KOLNP-2006-CORRESPONDENCE 1.1.pdf

3094-KOLNP-2006-CORRESPONDENCE.pdf

3094-KOLNP-2006-DESCRIPTION (COMPLETE) 1.1.pdf

3094-KOLNP-2006-EXAMINATION REPORT.pdf

3094-KOLNP-2006-FORM 1-1.1.pdf

3094-KOLNP-2006-FORM 18 1.1.pdf

3094-kolnp-2006-form 18.pdf

3094-KOLNP-2006-FORM 2-1.1.pdf

3094-KOLNP-2006-FORM 3 1.2.pdf

3094-KOLNP-2006-FORM 3-1.1.pdf

3094-KOLNP-2006-GPA.pdf

3094-KOLNP-2006-GRANTED-ABSTRACT.pdf

3094-KOLNP-2006-GRANTED-CLAIMS.pdf

3094-KOLNP-2006-GRANTED-DESCRIPTION (COMPLETE).pdf

3094-KOLNP-2006-GRANTED-FORM 1.pdf

3094-KOLNP-2006-GRANTED-FORM 2.pdf

3094-KOLNP-2006-GRANTED-SPECIFICATION.pdf

3094-KOLNP-2006-OTHERS 1.1.pdf

3094-KOLNP-2006-OTHERS PCT FORM.pdf

3094-KOLNP-2006-OTHERS.pdf

3094-KOLNP-2006-PETITION UNDER RULE 137.pdf

3094-KOLNP-2006-REPLY TO EXAMINATION REPORT.pdf