Title of Invention	A CINNAMIDE COMPOUND HAVING CELL ADHESION ANTI-INFLAMMATORY AND IMMUNE SUPPRESSIVE PROPERTIES
Abstract	ABSTRACT' EV/PCT/2001/01040/CHE "A cinnamide compound having cell adhesion anti-inflammatory and immune suppressive properties" The present invention relates to novel cinnamide compounds that are useful for treating inflammatory and immune diseases, to pharmaceutical compositions containing these compounds, and to method of inhibiting inflammation or suppressing immune response in a mammal.

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This annlicatioiiis a continuation-in-Dart of Amplication Serial Number )/l 14,097, filed December 29, 1998. Technical Field The present invention relates to compounds that are useful for treating lammaiory and immune diseases, to pharmaceutical compositions comprising thesf ■npounds, and to methods of inhibiting inflammation or suppressing immune ponsc in a mammal. Background Inflammation results from a cascade of events that includes vasodilation ompanied by increased vascular permeability and exudation of fluid and plasma teins. This disruption of vascular integrity precedes or coincides with an Itration of inflammatory cells. Inflammatory mediators generated at the site of tne iai lesion serve to recruit inflammatory cells to the site of injury. These mediator^ ;mokines such as IL-8, MCP-l, MIP-l, and RANTES, complement fragments an** lipid mediators) have chcmotactic activity for leukocytes and attract the inflammatory cells to the inflamed lesion. These chemotactic mediators which cause circulating leukocytes to localize at the site of inflammation require the cells to cross the vascular endothelium at a precise location. This leukocyte recruitment is accomplished by a process called cell adhesion. Celi adhesion occurs through a coordinately regulated series of steps that allow the leukocytes to first adhere to a specific region of the vascular endothelium and then cross the endothelial barrier to migrate to the inflamed tissue (Springer, T A., 1994, Traffic Signals for Lymphocyte Recirculation and Leukocyte Emigration: The Multistep Paradigm. Cell 76: 301-314: Lawrence, M. B.. and Springer, T. A.. 1991, Leukocytes' Roll on a Seleclin at Physiologic Flow Rates: Distinction from and Prerequisite for Adhesion Through Integrins, Ccll.65: 859-873: von Adrian. U., Chambeis, J. D., McEnvoy. L.M., Bargztze, R.F., Arfos, K..E. and Butcher. E.C., 1991, Two-Step Model of Leukocyte-Endothelial Cell Interactions in Inflammation. Proc. Natl. Acad. Sci. USA 88: 7538-7542; and Ley. K.. Gaehtgens. P.. Fennie, C, Singer, M.S., Lasky, L.H. and Rosen. S.D.,1991, Lectin-Like Cell Adhesion Molecule 1 Mediates Rolling in Mesenteric Venules in vivo, Blood 77: 2553-2555). These steps are mediated by famiiies of adhesion molecules such as integrins, Ig supergene family members, and selectins which are expressed on the surface of the circulating leukocytes and on the vascular endothelial cells. The first step consists of leukocytes rolling along the vascular endothelial cell lining in the region of inflammation. The rolling step is mediated by an interaction between a leukocyte surface oligosaccharide. such as Sialylated Le^is-X antigen (SLe*), and a selectin molecule expressed on the surface of the endothelial eel] in the region of inflammation. The selectin molecule is not normally expressed on the surface of endothelial ceils but rather is induced by the action of inflammatory mediators such as TNF-a andinterieukin-1. Rolling decreases the velocity of the circulating leukocyte in the region of inflammation and allows the cells to more firmJy_a«}herB to the endothelial cell. The firm adhesion is accomplished by the interaction of integrin molecules that are present on the surface of the rolling leukocytes and their counter-receptors (the Ig superfamily molecules) on the surface of the endothelial cell. The Ig superfamily molecules or CAMs (Cell Adhesion Molecules) are either dot expressed or are expressed at low levels on normal vascular endothelial, cells. The CAM's, like the selectins, are induced by the action of inflammatory mediators like TNF-alpha and IL-1. The final event in the adhesion process is the extravasation of leukocytes through the endothelial cell barrier and their migration along a chernotactic gradient to the site of inflammation. This transmigration is mediated by the conversion of the leukocyte integrin from a low avidity state to a high avidity state. The adhesion process relies on the induced expression of selecting and CAM's on the surface of vascular endothelial cells to mediate the rolling and firm adhesion of leukocytes to the vascular endothelium. ) The interaction of the intercellular adhesion molecule ICAM-I (cd54) on endothelial cells with the integrin LFA-1 on leukocytes plays an important role in endothelial-leukocyte contact. Leukocytes bearing high-affinity LFA-1 adhere to endothelial cells through interaction with 1CAM-1. initiating the process of extravasation from the vasculature into the surrounding tissues. Thus, an agent which blocks the ICAM- 1/LFA-l interaction suppresses these early steps in the inflammatory response. Consistent with this background, ICAM-I knockout mice have numerous abnormalities in their inflammatory responses. The present invention discloses compounds which bind to the interaction-domain (I-domain) of LFA-1, thus interrupting endothelial eel I-leukocyte adhesion by blocking the interaction of LFA-1 with 1CAM-1, ICAM-3, and other adhesion molecules. These compounds are useful for the treatment or prophylaxis of diseases in which leukocyte trafficking plays a role, notably acute and chronic inflammatory diseases, autoimmune diseases, tumor metastasis, allograft rejection, and reperfusion injury. The compounds of this invention arsdiaryl sulfides^ which arc substituted with a cinnamide moiety. The cinnamide functionality may be placed either ortho- Or para- to the linking sulfur atom, although para-substitution is preferable. - Appropriate substitution of both aromatic rings is tolerated, and can be used to modulate a variety of biochemical, physicochemical and pharmacokinetic properties. In particular the amide moiety is readily modified; a variety of secondary and tertiary amides are active, and alternatively a heterocyclic ring may be attached at this position. Modifications of this amide functionality are particularly useful in modulating physicochemical and pharmacokinetic properties. Summary of The Invention The present invention provides compounds of formula I, below, or a pharmaceutically-acceptable salt or prodrug thereof, wherein R„ R3, Rj, R4, and R, are independently selected from a. hydrogen, b. halogen, c. alkyi, d. haloalkyl, e. alkoxy, f. cyano, g. nitro, h. carboxaldehydc, and with the proviso that at least one of R, or R3 is a "cw-cinnamide" or a "trans-cinnamidc", defined as wherein K3 and R, are independently selected from a. hydrogen, and b. alkyl, c. carboxy alkyl, d. aikylaminocarbnnyl alkyl, and e. dialkylaminocarbonyl alky!. and R(0 and R,, are independently selected from a. hydrogen. b. alkyl, c. cycloalkyl, d. alkoxycarbonylalkyl, e. hydroxy alky I, f. heterocyciyl. g. heterocyctylalkyl, h. heterocyclylamino, i. substituted heterocyciyl, and j. substituted heterocyclylalkyt, or where NR^R,, is hetcrocyclyj or substituted heterocyciyl, where substituents are independently selected from 1) alkyl. 2) alicoxy, 3) alkoxyalkyl, 4) cyctoalkyl, 5) ary], 6) heterocyclyL 7) heterocyclylcarbonyl, 8) hcterocyclylalkylaminocarbonyl. 9) hydroxy, 10)hydroxyalkyl, 11) hydroxyalkoxyalkyl, 12) carboxy, 13)carboxyaHcyi, it) carDOxycaroonyi, 15) carboxaldehyde, 16) alkoxycarbonyl, 17) arylalkoxycarbonyl, 18)aminoalkyl, 19) aminoalkanoyl. 20) caiboxamido, 21) alkoxycarbonylalkyl. 22) carboxamidoalkyL 23) cyano, 24) tetrazolyl, 25) substituted tetrazolyl. 26) alkanoyl, 27) hydroxyalkanoyl. 28) alkanoyloxy, 29) alkanoyl ami no, 30) alkanoyloxy alky 1. 31) alkanoylaminoalkyl, 32) sulfonate, 33) alkylsulfonyl, 34) alkylsulfonylaminocarbonyl, 35) arylsulfonylaminocarbonyl, and 36) heterocyclytsulfonylaminocarbonyl, and wherein Ar is a substituted aryl or substituted heteroaryi group, where substitutions are independently selected from a. hydrogen, b. halogen, c. alkyl, d. aryl, e. haloalkyl, f. hydroxy, g. alkoxy, h. alkoxy alky I, i. alkoxycarbonyl, j. alkoxy alkoxy, k. hydroxy alkyl, 1. aminoalkyl, m. aminocarbonyl, n. alkyl(alkoxycarbonylalky l)aminoalkyl, o. heterocyclyl, p. heterocyclylalkyl, q. substituted heterocyclylalkyl, r. carboxaldehyde, s. carboxaldehyde hydrazone, t- carboxamide, u. alkoxycarbonylalkyl, \. caiboxy, w. carboxyalkyl, x. hydroxycarbonylalkyl (carboxyalkyl), y. hydroxyalkylaminocarbonyl, z. cyano, aa. amino, bb. heterocyclylalkylamino, tc. hetetocyclylalkylaminocarbonyl, and dd. ■'/ranr-cinnamide". Additionally provided are methods of treatment or prophylaxis in which the inhibition of inflammation or suppression of immune response is desired, comprising administering an effective amount of a compound of formula I. Still further provided are pharmaceutical compositions containing compounds of formula I. Detailed Description The lerm "alkanoyl" as used herein refers to an alkyl group attached to the parent molecular group through a carbonyl group. The term "alkanoylamino" as used herein refers to an alkanoyl group attached to the parent molecular group though an amino group. The term "alkanoyl ami noalky I" as used herein refers £o an alkanoyl amino group attached to the parent molecular group through an alkyl group: The term "alkanoyioxy" as used herein refers to an alkanoyl group attached to the parent molecular group through an oxygen radical. The term " alkanoyioxy alky!" as used herein refers to an afkanoyloxy group attached to the parent molecular group through an alkyl group. The term "alkoxy" as used herein refers to an alkyl group attached to the parent molecular group through an oxygen atom. The term "alkoxyalkoxy" as used herein refers lo an alkoxy group attached to the parent molecular group through an alkoxy group. The term "alkoxyalkyl" as used herein refers to an alkoxy group attached to the parent molecular group through an alkyl group. The term "alkoxycarbonyl" as used herein refers to an alkoxy group attached to the parent molecular group through a carhonyl group. The term "alkoxycarbonylalkyl" as used herein refers to an alkoxycarbonyl group attached to the parent molecular group through an alkyl group. The term "alkyl" as usea rierein reiers 10 a saiuraica siraigm or oranched chain group of 1-10 carbon atoms derived from an alkane by the removal of one hydrogen atom. The term "alkyl{alkoxycarbonyialky!)amino" as used herein refers to an amino group substituted with one atkyl group and one alkoxycarbonylalkyl group. The term "alkyl(alkoxycarbonylalkyl)aminoalky!" as used herein refers to an alky!(alkoxycarbonylalkyl)amino group attached to the parent molecular group through an alkyl group. The term "alkylene" as used herein refers to a divalent group of 1-10 carbon atoms derived from a straight or branched chain alkane by the removal of two hydrogen atoms. The term "alkylsulfonyl" as used herein refers to an alkyl radical attached to the parent molecular group through an -SO-- group. The term "alkylsulfonylarninocarbonyl" as used herein refers to an alkylsulfonyl group attached to the parent molecular group through an aminocarbonyl group. The term "amino" as used herein refers to a radical of the form -NRISR|„ or to to a radical of the form -NR,8-, wriere R|t and R„ are independently selected from hydrogen, alkyl or cycloalkyl. The term "aminoalkanoyi1" as used herein refers to to an amino group attached to the parent molecular group through an alkanoyl group. The term "arainoalkyl" as used herein refers to an amino group attached to the parent molecular group through an alkyl group. The term "arninocarborLyl" as used herein refers to an amino group attached to the parent molecular group through a carbonyl group. The term "aryl" as used herein refers to a mono- or tricyclic carbocyclic ring system having one or two aromatic rings. The aryl group can also be fused to a cyclohexane. cyclohexene, cyclopentane or cyclopentene ring. The aryl groups of this invention can be optionally substituted with alkyl. halogen, hydroxy, or alkoxy substituents. The term "arylalkoxy" as used herein refers to an aryl group attached to the parent molecular group through an alkoxy group. I he term "arylalkoxycarbonyl" as used herein refers to an arylalkoxy group attached to the parent molecular group through a carbonyl group. The term "arylsulfonyl" as used herein refers to an aryl radical attached to the parent molecular group through an -SO,- group. The term "arylsulfonylaminocarbony 1" as used herein refers to an arylsulfonyl group attached to the parent molecular group through an aminocarbonyl group. The term "carta oxal deny de" as used herein refers to the radical -CHO. The term "carboxaldehyde hycrazone" as used herein refers to the radical -CH=N-NRmR,„ where RI0 and R,, are independently selected from hydrogen, alkyl or cycloaikyl. The terms "carboxamide" or "carboxamido" as used herein refer to an amine group attached to the parent molecular group through a carbonyl group. The term "carboxamidoalkyl" as used herein refers to a carboxamido group attached to the parent molecular group through an alkyl group. The term "carboxy" as used herein refers to Ihe radical -COOH. The term "carboxyalkyl" as used herein refers to a carboxy group attached to the parent molecular group through a alkyl group. The term '"carboxy carbonyl" as used herein refers to a carboxy group attached to the parent molecular group through a carbonyl group. The term "cyano" as used herein refers to the radical -CN. The term "cycloalkyl" as used herein refers to a monovalent saturated cyclic or bicyclic hydrocarbon group of 3-12 carbons derived from a cycloalkane by the removal of a single hydrogen atom. Cycloalkyl groups may be optionally substituted with alkyl. alkoxy, halo, or hydroxy subsiiruents. The terms "halo" or "halogen" as used herein refers to F. CI. Dr. or 1. The term "haloalkyJ" as used herein refers to an alky! group subsliiuied with one or more halogen atoms. The terms "hetecocycle" or "heterocyclyl" represent a 4-, 5-, 6- or 7-membered ring containing one, two or three heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulfur. The 4- and 5-mcmbered rings have zero to two double bonds and the 6- and 7-membercd rings have zero to three double bonds-The term "heterocycle" or "heterocyclic" as used herein additionally refers to hicyclic. tricyclic and tetracyclic groups in which any of the above heterocyclic rings is rused to one or two rings independently selected from an aryl ring, a cyciohexane ring, a cyclohexcne ring, a cyclopentane ring, a cyclopentene ring or another monocyclic heterocyclic ring, lleterocycles include acridinyl, benzimidazolyl, benzofiiryl, benzothiazoiyl, benzothienyl, benzoxazolyl, biotinyf, cinnolinyl, dihydrofuryl, dihydroindolyl, dihydropyranyl, dihydrothienyl, dithiazolyl, furj'l, homopiperidinyl, imidazolidinyl, imidazolinyl, imidazolyl, indolyl. isoquinolyl, isothiazolidinyl, isodiiazolyl, isoxazolidinyl, isoxazolyi. morphoJinyl, oxadiazolyl, oxazolidinyl, oxazolyl, piperazinyl, pipecidinyl, pyranyl, pyrazolidinyl, pyrazinyl, pyrazolyl, pyrazolinyl, pyridazinyl. pyridyl, pyrimidinyl, pyrimidyl, pyrrolidinyl, pyrrolidin-2-onyl, pyrrolinyl, pyrrolyl, quinolinyl, quinoxaloyl. tetrahydrofuryl, telrahydroisoquinolyl, tetrahydroquinolyt, tctrazolyl. thiadiazolyl. thiazolidinyl, thiazolyl, thienyl, thiomorpholinyl. triazolyl, and the like. Heterocyclics also include bridged bicyclic groups where a monocyclic heterocyclic group is bridged by an alkylene group such as and Z* are independently selected from -CH2-. -CH2NH-. -CH20-, -NH- and -O-, with the proviso that at least one of X* and Z* is not -CH,-. and Y* is selected from -C(0)- and -{C(R")2)v -, where R" is hydrogen or alkyl of one to four carbons, and v is 1-3. These heterocycles include 1,3-benzodioxoiyl, 1,4.benzodioxanyl, 1,3* benzimidazol-2-one and the like. The heterocycle groups of this invention can be optionally substituted with alkyl, halogen, hydroxy or alkoxy substituents. The term "heterocyclylalkyl" as used herein refers to an heterocyclic group attached lo the parent molecular group through an alkyl group. The lerm "heterocyclylalkylamino" as used herein refers to an heterocyclylalkyl group attached to the parent molecular group through an amino group. The term "heterocyclylalkylaminocarbonyl" as used herein refers to a heierocyclylalkylamino group attached to the parent molecular group through a carbony! group. The term "heterocyciylamino" as used herein refers to a heterocyclyl group attached to the parent molecular group through a amino group. The term "heterocyclylcarbony 1" as used herein refers to a heterocyclyl group attached to the parent molecular group through a carbonyl group. The term "heterocyclylsulfonyl" as used herein refers to a heterocyclyl radical attached to the parent molecular group through an -S02- group. The term "hctcrocydylsulfonylaminocarbonyr as used herein refers to a heterocyclylsulfonyl group attached to the parent molecular group through an aminocarbonyl group. The term" hydroxy alkanoyl" as used herein refers to an hydroxy radical attached to the parent molecular group Through an alkanoyl group. The term "hydroxyalkoxy" as used herein refers to an hydroxy radical attached to the parent molecular group through an alkoxy group. The term "hydroxy alkoxy alky 1" as used herein refers to an bydroxyalkoxy group attached to the parent molecular group through an alkyl group. The term "hydroxyalkyl" as used herein refers to an hydroxy radical attached to the parent molecular group through an alkyl group. The term "hydroxyalky lam inocarbonyl" as used herein refers lo an hydroxyalkyl group attached lo the parent molecular group through an am inocarbonyl group. The term "perfluoroalkyl" as used herein refers to an alkyl group in which all of the hydrogen atoms have been replaced by fluoride atoms. The term "phenyl" as used herein refers to a monocyclic cacbocyclic ring system having one aromatic ring. The phenyl group can also be fused to a cyclohcxane or cyclopenlane ring. The phenyl groups of this invention can be optionally substituted with alkyl, halogen, hydroxy or alkoxy substituents. The term "pharmaceutically-acceptablc prodrugs" as used herein represents those prodrugs of the compounds of the present invention which are. within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals with undue toxicity, irritation, allergic response, and the like. commensurate with a reasonable benefit/risk ratio, and effective for their intended use, as well as [he zwitterionic forms, where possible, of the compounds of the invention. The term "prodrug," as used herein, represents compounds which are rapidly transformed in vivo to the parent compound of the above formula, for example, by hydrolysis in blood. A thorough discussion is provided in T. Higuchi and V. Stella, Pro-drugs as Novel Delivery Systems, Vol. 14 of the A.C.S. Symposium Series, and in Edward B. Roche, ed., Bioreversible Carriers in Drug Design, American Pharmaceutical Association and Pergamon Press. 1987, both of which are incorporated herein by reference. The term "sulfonate" as used herein refers to the radical -SO,H The term "tetrazole" or "tctrazolyl" as used herein refers to the heterocyclic radical -CNjH.. The term "thioalkoxy" as used herein refers to an alky) group attached to the parent molecular group through a sulfur atom. Compounds of the present invention can exist as stereoisomers wherein asymmetric or chiral centers are present. These compounds are designated by the symbols "R" or "S," depending on the configuration of substituents around the chira] carbon atom. The present invention contemplates various stereoisomers and mixtures thereof. Stereoisomers include enantiomers and diastcreomers. and mixtures of enantiomers or diastereomers are designated (i). Individual stereoisomers of compounds of the present invention can be prepared synthetically from commercially available starting materials which contain asymmetric or chiral centers or by preparation of raccmic mixtures followed "by resolution wdl-'known to those of ordinary skill in the art. These methods of resolution are exemplified by (1) attachment of a mixture of enantiomers to a chiral auxiliary, separation of the resulting mixture of diastereomers by recrystallization or chromatography and liberation of the optically pure product from the auxiliary, (2) salt formation employing an optically active resolving agent, or (3) direct separation of the mixture of optical enantiomers on chiral chromatographic columns. Geometric isomers can also exist in the compounds of the present invention. The present invention contemplates the various geometric isomers and mixtures thereof resulting from the arrangement of substituems around a carbon-carbon double bond or arrangement of substituents around a carbocyclic ring. Substituents around a carbon-carbon double bond are designated as being in the Z or E configuration wherein the term "Z" represents substituents on the same side of the carbon-carbon double bond and the term "E" represents substituents on opposite sides of the carbon-cJaWn AouWe bono.. The arrangcmeni oi" subsivmenis around a carbocyclic ling are designated as cis or trans wherein the term "cis" represents substituents on the same side of the plane of the ring and the term "trans" represents substituents on opposite sides of the plane of the ring. Mixtures of compounds wherein the substituents are disposed on both the same and opposite sides of plane of the ring are designated cis/tians. As is apparent from the foregoing descriptions, the compounds of Formula 1 afe useful in a variety of forms, i.e., with various substitutions as identified. Examples of particularly desirable compounds are quite diverse, and many are mentioned herein. Included are compounds in which R, is a "cis-cinnamide" or a "trans-cinnamide", and R3 is hydrogen; or where R, is a "cis-cinnamide" or a "trans-cinnamide", and R, is hydrogen, or R„ R;, and R, are each independently hydrogen or alkyl, and Rj is halogen, haloalkyl or nitro. Further preferred compounds include those as above wherein Rl0 and RH arc each independently hydrogen, alkyl, cycloatkyl, alkoxycarbonylaalkyl, hydroxyalkyl, or heterocyclylalkyL or where NRI0R| i is heterocyclyl or substituted heterocyclyl, and where Ar is aryl, substituted aryl, heteroaryl, or substituted heteroaryl. Compounds of the present invention include: (2,4-Dichlorophenyl)r2-{£-((6-hydroxyhexylamino)carbonyl)ethenyi)phenyl] sulfide; (2,4-Dichlorophenyl)[2-(F-({3-(l-imidazo]yl)propylamino)carbonyl)ethenyl)phenyl] sulfide; (2,4-Dichiorophenyl)[2-chloro-4-(£-((2-hy droxy ethy 1 ami no)carbony l)ethenyl)phenyl] sulfide; (2,4-Dichlorophenyl)[2-chloro-4-(£-((6hydroxyhexylamino)carbonyl)ethenyl)phenyl] Sulfide; (2,4-Dichlorophenyl)[2-chioro-4-( £-((bis-(2-hydroxyethyl)amino)carbony])ethenyl) phenyl] sulfide; (2,4-Dichlorophenyl)[2-chloro-4-{ £- (2,4-Dichlorophenyl)[2-chloro-4-( £-((1-morpholinyi)carbony!)ethcnyl)phenyl] sulfide; (2,4-Dichloropheoyl)[2-chlorO'4-(£-((4-methy]piperazin-l-yl)carbonyl)elhcnyl)phenyl] sulfide; (2-Bromophenyl)[2-chloro-4-(£-((4-hydroxypiperidin-1-yl)carbon>'l)cthenyl)pheiiyl] sulfide; (2-Bromopheny])[2-Chloro-4-( £-((piperidin-l-yl)carbonyl) ethenyl)phenyl] sulfide; (2,4-Dichloropheny])[2-chJoro-4-(£-((3-carboxypiperidirv-l- yl)carbonyl)ethenyl)phenyl] sulfide; ethettyOphenyl] sulfide; (2-Meihylpheny])[2-trifluoromethyl-4-{£-((3-(l-pyrrolidin-2-onyl)propylamino}carbonyl) ethenyl)phenyl] sulfide; (2-Methylphenyl)(2-trifluoromethyl-4-(£-((cyclopropyIamino)carbonyl)eiheny]) phenyl] sulfide; yl)carbonyl) ethenyl)phenyl] sulfide; (2,4-Dichloropheny])[2-nitro-4-(£-((4-(diethylaminocarbony])piperazin-l-yl)carbonyl) ethenyl)phenyl] sulfide; sulfide; (2-ChIoropheny])[2-chloro-4-(£-((4-aceiylpiperazin-l-yl)carbonyl))2-propenyl)phenyl] sulfide; (l^I-MoiphoUnylmethylJphenylJP-chloro^-CE-ttl-moTpholinylJcarbonyDethenyl) (2,4-Dichlorophcnyl)[2-bromo-4-( £-((3-(l-pyrrolidin-2-only)propylamino)carboriyl) ethenyl)phenyl] sulfide; (2,4-Dichlorophenyl)[2-fonnyl-4-(£-((l-morpholmyl)carbony3)eihcnyl)phcnyl] sulfide; (2-Isopropy]phenyl)[2-nitro-4-(£-((2-carboxy-4-rer/-butoxycarbonylpiperazin-l-yl)carbonyl)ethenyl) phenyl] sulfide; (2-Isopropylpheny!)f2-trifluoromethy]-4-(£-((4-ac«ylpiperazin-]-yl)carbonyl) ethenyl) phenyl] sulfide; (5-Indolyl)[2-chloro-4-{ £-((4-aceIyipiperazin-l-yl)carbonyl) ethenyl) phenyl] sulfide; (5-Beni"odioxolyl)[2-chloro-4-(£-((4-acetylpiperazin-l-yl)carbonyl) ethenyl) phenyl] sulfide; (2-lsopropylpheny])[2-niiro-4-(£-((2-carbomethoxypipcra2dn-l-yl)carbonyl)eihenyI) (2-lsopropy lpheny 1) [2-nitro-4-( £-((3 - (py ri dine-4-methy laminocarbo ny l)-4-/erf-butoxycarbonyipiperazin-l-yl)carbonyl)ethenyl) phenyl] sulfide; (2-Ethoxyphenyl)-[2-chloro-4(E-[(morpholin-l-yl)cflrbonyi]etheny])phenyl]sulfide; (2-Methoxypheny])[2-niiro-4-(£-((4-acetylpiperazin-l-y])carbony])ethenyl)phenyl]sulfide; (2-Isopropylpheny])[2-nitro-4-( £-((3-dimethylaminocarbony!-4-acetylpipcrazin-l-yi)carbonyt)elheny!) phenyl] sulfide; (2-Isopropylphenyl)[2-nitro-4-(£'-((3-(l-niorpholitiocarbonyl}-4-/er/- (2-lsopropylphenyl)[2-nitro-4-( £-((4-fe«-butoxycarbonylpiperazin-1 -yl)carbonyl)ethenyl) phenyl] sulfide; (2-Isopropylphenyl)[2-nilro-4-(£'-((4-mcthoxycarbonylpipera2in-l-yl)carbonyl)elheiiyl) phenyl] sulfide; Pheny![2-nitro-4-(£-((4-acetylpiperazin-l-yI)carbonyl)ethcnyI)phenyl]su]tide; (2-Dimethylaminophenyl)[2-nitro-4-( ^-((4-acetylpiperazin-l -yl)carbotiyl) ethenyl) phenyl] sulfide; (2,^Dimethylpheny])[2-nitro-4-(£-((4-acetylpiperazin-I-yl)carbonyl)ethenyl)phcnyl]sulfide; (2,5-Dtmethylphenyl)[2- nitro-4-( £-((4-acetyIpiperazin-1 -yl)carbonyl)cthenyl)phenyl]su]fide; (2-lsopropylpheny])[2-nitro-4-C£'-((4-(pyridine-3-carbonyl)piperazin-l-yl)carbonyl)ethenyl) phenyl] sulfide; (2-Isopropylphenyl)[2-nitro-4-(£.((2-carbomeihoxy-4-melhoxycarbonylpiperazJn-l- (2-Eihoxypheny])[2-lrifluoromethy1-4-(£-((4-acetylpipcrazin-I-yl)carbonyl)ethen)'l) phenyl] sulfide; (2-Ethoxyphenyl)P-trifluoromethy l-4-(£-((4-(ethoxycarbonyl)piperazm-1 - I i (2-Isopropylphenyl)[2-nitro-4-(£-((4-caitioxamidopiperazin-l-yl)carbony!)etheny!) phenyl] sulfide; (2-Isopropylpheny!)[2-nitro-4-(£-((4-methylaminocarbonylpiperazin-1-yl)carbonyl)ethenyl) phenyl] sulfide; l (2-Isopropy]pbcnyl)[2-nitro-4-(£,-{(3-carboxam]dopiperazin-i-yl)carbonyl)eiheny]) phenyl] sulfide; (2-Isopropyiphcny])[2-nitro-4-(£-((3-carbomelhoxy-4-oxopiperidin-l-yl)carbonyl}edienyl) phenyl] sulfide; l-Methylindol-5-y])[2-chloro-4-(£-((4-acciylpiperazin-I-yl)carbooyl)ethcnyl) henyl] sulfide; 3enzodioxan-6-yl)[2-niiro-4-(£-((4-acetyipiperazin-l-yI)carbonyI)ethenyl) phenyl] ilfide; (Benzodioxan-6-yl)[2-nitro-4-( £,-((4-(«7-butoxycarbonylpiperazin-l -yl) carbonyl)ethenyli phenyl] sulfide; (2-Isopropylphenyl)[2-nitro-4-{£-((iyn-3,5-dimethylmorpholin-l-y!)carbonyl)ethenyl) phenyl] sulfide; (Indol-6-yl)[2-chloro-4-( £- (1-Ethyl,3-(dimethylaminomethyl)indol-7-yi)[2-chloro4-( £-((4-acetylpiperazin-l-yl)carbonyl)ethenyl) phenyl] sulfide; (5-Ethoxybenzodioxan-6-yl}[2-chloro-4-(£-((4-acetyipiperazin-l- (2-Isopropylphenyl)[2-nilro-4-(£-(((3-cthanesulfonylaminocarbonyl)piperidin-l-yl)carbonyl)ethenyl) phenyl] sulfide; (2-Isopropy I phenyl) [2-nitro-4 -(£-((( 3-(4-methy Ipiperazine) sulfonylaminocarbonyl)piperidin-l-yl)carbony])ethenyl) phenyl] sulfide; (2-Isopropylphcnyl)r2-nitro-4-(£-(((3-p-toluenesulfonylaminocarbonyl)pipcridin-l- (3-Bromophcnyl)[2-nitrc»-4-(£-((4-carboeihoxypyiTolidin-l-y])carbonyl)eihenyl) phenyl] sulfide; (2-(Hydroxymethyl)-benzodioxaii-6-yl)E2-chloro-4-(£-((4-acetylpipera2iti-l- (&enzodioxan-6-yl)[2-trifiuoromethyl-4-t£-(l2-carboethoxypiperidui-l-yl) carbonyl)ethenyl) phenyl] sulfide; (Benzodioxan-6-yI)[2-nitro-4-(£-((4-carboxypiperidin-l-yl)carbonyl)ethenyl) phenyl] sulfide; (2-Isopropylphcnyl)[2-iiiln>-4-(£,-((3-cyanomorpholiti-l-yl)carbonyI)elheny]) phenyl] sulfide; (2-IsopropyIphcnyl)[2-nilro-4-(£-((3-carboethoxymQrpholin-l-yl)carbonyl)eiheoyl) phenyl] sulfide; (Benzo dioxan-6-y 1) (2 -trifl uorom etby I -4-( E- ((2-carboxy-4- methoxycarbonylpiperazin-1-yl) carbonyl)eihenyl) phenyl] sulfide; (Benzod ioxan-6-y I ) [2-trifluoromethy 1 -4-(£- ((morphol in-1 -y 1) carbony 1 Jctheny i) (a-IsopropylphenyOP-nitro-Hf-tCS-ftelrazol-S-yOpiperidin-l-yOcaxbonylXthenyl) phenyl] sulfide; (I-Meihylindol-5-y!)[2-ch!oro-4^£.((3-carbocthoxypiperidin-l-yl)carbonyl)eiheny|) (Benzodioxan-6-yl)[2-trifluoromethyl-4-(E-{(4- ((ethanesulfonylamino)carbonyl)piperidin-l-yl) carbonyljethenyl) phenyl] sulfide; (Benzodioxan-6-yI)[2-trifluoromethy i-4-{£'-((2(lctrazol-5-yl)morpholm-1 - (2-IsopropyIphenyI}[2-nitro-4-(£-((3-(acctoxymethyI)morphoiin-I-yl)carbonyl)ethenyl) phenyl] sulfide; (2-Isopropylphenyl)[2-nttro-4-(£-{(3-(aminomethy!)tnQrpholin-l- Benzodioxan-6-y])[2-chloro-4-(£-{(4-(/erf-butoxycarbonyl)piperazin-l-yl) ;arboiiy!)etheny]) phenyl] sulfide; (Benzodioxan-6-yl)[2-chloro-4-(£-((2-carboxypipcridin-l-yl)carbonyl)ethenyl) ihenyl] sulfide; (Beii7odioxaii-6-yl)[2,3-dich]oro-4-(£,-((4-acetylpiperazin-l-yl)carbonyl)ethenj'l) phenyl] sulfide; (Benzodioxan-6-yl)[2,3-dichloro-4-(£-((3-carboethoxypiperidin-I-yl) carbonyl)ethenyl) phenyl] sulfide; (l-Mcthylindol-5-yl)t2,3-dichloro-4-(E-t(3-carboethoxypipcridin-l-yl) carbonyl)ethenyl) phenyl] sulfide; (I-MethylindoI-5-yl)[2,3-dich]oro-4-{£-((3-carboxypipcridin-l-y])carbonyl)eihenyI) phenyl] sulfide; (2-lsopropy]phenyl)[2,3-difluoro-4-{£-((4-carboxypipcridin-l-yl)carbonyI)ethenyl) phenyl] sulfide; (Ben2odtoxan-6-yl)[2-trifluoTomeihyl.4-(£-((3-ethoxycari»nylpyTTolidin-l-yl)carbonyl)etheny!) phenyl] sulfide (Benzodioxan-6yl)[2,3-bis(trifluoroiiieihyl)-4-(E-((4-carboxypiperidin-l-y l)carbony l)etheny IJpheny ] ] sul fi de; (2-M ethoxy pheny 1) [2,3 -dichloro-4-(E-((4-(carboxymethy lamino)carbony 1-piperidin-l-yl)carbonyl)ethenyl)phenyl] sulfide; (2-Methoxyphenyl) [2,3^ichloro^£-((4-amino-4-carlwxypiperidin-]-yI)carbonyl)etheny])pheDyl] sulfide; (2-Methoxyphenyl)[2,3-dichloro-4-{(4-furoylpiperazin-l-yi)caTbonyl)ethenyl)phenyl] sulfide; Pharmaceutical Compositions and Methods of Treatment The present invention also provides pharmaceutical compositions which comprise compounds of the present invention formulated together with one or more pharmaceutically-acceptable carriers. The pharmaceutical compositions may be specially formulated for oral administration in solid or liquid form, for parenteral injection, or for rectal administration. The pharmaceutical compositions of this invention can be administered to humans and other animals orally, recially, paremerally, inlracisternally. -intra vaginally, intraperitoneally, topically (as by powders, ointments, or drops), bucally, or as an oral or nasal spray. The term "parenteral" administration as used herein refers to modes of administration which include intravenous, intramuscular, intraperitoneal, intrastcrnal, subcutaneous and intraarticular injection and infusion. Pharmaceutical compositions of this invention for parenteral injection comprise pharmaceuticalJy-acceptable sterile aqueous or nonaqueous solutions, dispersions, suspensions or emulsions as well as sterile powders for reconstitutbn into sterile injectable solutions or dispersions just prior to use. Examples of suitable aqueous and nonaqueous carriers, diluents, solvents or vehicles include water. ethanol, polyois (such as glycerol, propylene glycol, polyethylene glycol, and the like), and suitable mixtures thereof, vegetable oils (such as olive oil), and injectable organic esters such as ethyl oleate. Proper fluidity can be maintained, for example, by the use of coating materials such as lecithin, by the maintenance of the required particle size in the case of dispersioa'?, and by the use of surfactants. These compositions may also contain adjuvants such as preservative, wetting agents, emulsifying agents, and dispersing agents. Prevention of the action of microorganisms may be ensured by the inclusion of various antibacterial and antifungal agents, for example, paraben, chlorobutanol, phenol sorbic acid, and the like. It may also be desirable to include isotonic agents such as sugars, sodium chloride, and the like. Prolonged absorption of the injectable pharmaceutical form may be brought about hy the inclusion of agents which delay absorption such as aluminum monostcaratc and gelatin. In some cases, in order 10 prolong the effect of the drug, it is desirable to slow the absorption of the drug from subcutaneous or intramuscular injection. This may be accomplished by the use of a liquid suspension of crystalline or amorphous material with poor water solubility. The rate of absorption of the drug then depends upon its rate of dissolution which, in lum, may depend upon crystal size and crystalline form. Alternatively, delayed absorption of a parenterally administered drug form is accomplished by dissolving or suspending the drug in an oil vehicle. Injectable depot forms are made by forming microencapsule matrices of the drug in biodegradable polymers such as polylactide-polyglycolide. Depending upon. IP I the ratio of drug to polymer and the nature of the particular polymer employed, the rate of drug release can be controlled. Examples of other biodegradable polymers include poly(orthoesters) and poly (anhydrides). Depot injectable formulations are also prepared by entrapping the drug in liposomes or micraemulsions which are compatible with body tissues. The injectable formulations can be sterilized, for example, by filtration through a bacterial-retaining filter, or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersed in sterile water or other sterile injectable medium just prior to use. Solid dosage forms for oral admini strati on include capsules, tablets, pills, powders, and granules, in such solid dosage forms, the active compound is mixed with at least one inert, pharmaceutically-acceptable excipient or carrier such as sodium citrate or dicalcium phosphate and/or (a) fillers or extenders such as starches, lactose, sucrose, glucose, mamutol. and silicic acid, (b) binders such as, for example, carboxy methyl cellulose, alginates, gelatin, polyvinylpyrrolidone, sucrose, and acacia, (c) humectants such as glycerol, (d) disintegrating agents such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate, (e) solution retarding agents such as paraffin, (f) absorption accelerators such as quaternary ammonium compounds, (g) wetting agents such as, for example, cetyl alcohol and glycerol monostearate, (h) absorbents such as kaolin and bentonim clay, and (I) lubricants such as talc, calcium stearate, magnesium stcarate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof. In the case of capsules, tablets and pills, the dosage form may also comprise buffering agents. Solid compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polyethylene glycols and the like. The solid dosage forms of tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings and other coatings well known in the pharmaceutical formulating art. They may optionally contain opacifying agents and can also be of a composition that they release the active ingredient(s) only, or preferentially, in a certain part of the intestinal tract, optionally, in a delayed manner. Examples of embedding compositions which can be used include polymeric substances and waxes. The active compounds can also be in micro-encapsulated form, tf appropriate, with one or more of the above-mentioned excipients. Liquid dosage forms for oral administration include pharmaceuti'caKy-acceptable emulsions, solutions, suspensions, syrups and elixirs. In addition to the active compounds, the liquid dosage forms may contain inert diluents commonly used in the art such as, for example, water or other solvents, solubilizing agents and emuisifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoaie, propylene glycol, 1,3-butylene glycol, dimethyl formamide, oils (in particular, cottonseed, groundnut, com, germ, olive, castor, and iesame oils), glycerol, tetrahydrofurfury] alcohol, polyethylene glycols and fatty acid ssters of sorbitan, and mixtures thereof. Besides inert diluents, the oral compositions can also include adjuvants such is wetting agents, emulsifying and suspending agents, sweetening, flavoring, and perfuming agents. Suspensions, in addition to the active compounds, may contain suspending igents as, for example, ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bemomte, agar, igar, and tragacanth, and mixtures thereof. Compositions for rectal or vaginal administration are preferably suppositories which can be prepared by mixing the compounds of this invention with suitable noiv. rritating excipients or carriers such as cocoa butter, polyethylene glycol or a suppository wax which are solid at room temperature but liquid at body temperature uid therefore melt in the rectum or vaginal cavity and release the active compound. Compounds of the present invention can also be administered in the form of iposomes. As is known in the art, liposomes are generally derived from jhospholipids or other lipid substances. Liposomes are formed by mono- or multi-amellar hydrated liquid crystals that are dispersed in an aqueous medium. Any non-oxic, physiologically-acceptable and metabolizable lipid capable of forming iposomes can be used. The present compositions in liposome form can contain, in addition to a compound of the present invention, stabilizers, preservatives, excipients, and the like. The preferred lipids are the phospholipids and the phosphatidyl cholines (lecithins), both natural and synthetic. Methods to form liposomes are known in the an. See, for example, Prescott, Ed., Methods in Ceil Biology. Volume XIV, Academic Press, New York, N.Y. (1976), p. 33 et seq. The compounds of the present invention may be used in the form of pharmaceutically-acceptable salts derived from inorganic or organic acids. By '■pharmaceutically-acceptable salt'" is meant those salts which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and ' lower animals without undue toxicity, irrimxion. allergic response and the Vke, and are commensurate with a reasonable benefit/risk ratio. Pharmaceutically-acceptable salts are well-known in the art. For example, S. M. Berge. eta!. Describe pharmaceutically-acceptable salts in detail in J. Pharmaceutical Sciences, 1977. 66: l et seq. The salts may be prepared in situ during the final isolation and purification of ' the compounds of the invention or separately by reading a free base function with a suitable acid. Representative acid addition salts include acetate, adipate. alginate, citrate, aspartate, benzoate, benzenesulfonate. bisulfate, butyrate, camphorate, camphorsulfonate, dighiconatc, glycerophosphate, hemisulfate, heptanoate. hexanoiue, fumarate, hydrochloride, hydrobromide, hydroiodide. 2-hydroxy ethane sulfonate ' (isethionate), lactate, maleate, methanesulfonate. nicotinate, 2-naphthalenesulfonate, oxalate, pamoate, pectinate, persulfaie, 3-phenyl pro pi on ate. picrate, pivalate, propionate, succinate, tartrate, thtocyanate, phosphate, glutamate. bicarbonate, p- toiuenesulfonate and undecanoate. Also, the basic nitrogen-containing groups can be quatemized with such agents as lower alkyl halides such as methyl, ethyl, propyl, and butyl chlorides, bromides and iodides; dialkyl sulfates iike dimethyl, diethyl, dibutyl and diamyl sulfates; long chain halides such as decyl, lauryl, myristyl and stearyl chlorides, bromides and iodides; arylalkyl halides like benzyl and phenethyl bromides and others. Water or oil-soluble or dispersible products are thereby obtained. Examples of acids which may be employed to form pharmaceutically acceptable acid addition salts include such inorganic acids as hydrochloric acid, hydrobromic acid, sulphuric acid and phosphoric acid and such organic acids as oxalic acid, maleic acid, succinic acid and citric acid. Basic addition salts can be prepared in situ during the final isolation and purification of compounds of this invention by reacting a carboxylic acid-containing moiety with a suitable base such as the hydroxide, carbonate or bicarbonate of a pharmaceutically acceptable metal cation or with ammonia or an organic primary, secondary or tertiary amine. Pharmaceutic a ily- acceptable basic addition salts inclack cations based on alkali metals or alkaline earth metals such as lithium, sodium. potassium, calcium, magnesium and aluminum salts and the like and nontoxic quaternary ammonia and amine cations including ammonium, tctramethylammonium. tetraethyl ammonium, methylaminc, dimethylamine, tri methyl amine, triethylamine, diethylamine, ethylamine and the like. Other representative organic amines useful i'or the formation of base addition salts include ethylenediamine, ethanolamine, diethanolamine, piperidine, piperazine and the like. Dosage forms for topical administration of a compound of this invention nclude powders, sprays, ointments and inhalants. The active compound is mixed inner sterile conditions with a pharmaceutically-acceptable carrier and any needed reservatives, buffers, or propellants which may be required. Opthalmic brmulations, eye ointments, powders and solutions are also contemplated as being vithin the scope of this invention. Actual dosage levels of active ingredients in (he pharmaceutical compositions )f this invention may be varied so as to obtain an amount of the active compound(s) hat is effective to achieve the desired therapeutic response for a particular patient, impositions, and mode of administration. The selected dosage level wil! depend ipon the activity of the particular compound, the route of administration, the severity if the condition being treated, and the condition and prior medical history of the patient being treated. However, it is within the skill of the art to start doses of the compound at levels lower than required for to achieve the desired therapeutic effect and to gradually increase the dosage until the desired effect is achieved. Generally dosage levels of about 0.1 to about 50 mg. men; preferably nf about 5 to about 20 mg of active compound per kilogram of body weight per day are administered orally or intravenously to a mammalian patient. If desired, the effective daily dose may be divided into multiple doses for purposes of administration, e.g. two to four separate doses per day. Preparation of Compounds of the Invention The compounds and processes of the present invention may be better understood in connection with the following synthetic Schemes which illustrate the methods by which the compounds of the invention can be prepared. Scheme ! describes the synthesis of a typical cinnamide-substituted diaryl sulfide 4 through an aldehyde intermediate 2. Aldehyde 2 is prepared by reaction of a thiophenol (for example 2.4-dichlorothiophenol, 2-bromoihiophenoi. or the like) with halo-substituted benzaldehyde derivative 1 (e.g. 2-chlorobenzaldehydc, 3-chloro,4-fluorobcnzaldehyde, or the like) in the presence of base (e.g. sodium carbonate, triethylamine, or the like) and a polar solvent (e.g. dimethylformamide, dimethy [sulfoxide, or the like). The aldehyde group is homologated to the corresponding cinnamic acid 3, using an acetate equivalent (for example, malonic I acid, triethoxypbosphonoacetale, or the like) in the presence of an appropriate base and solvent. In some cases, it may be necessary to hydrolyze an intermediate ester (for example using sodium hydroxide in alcohol). The acid group is activated (for example using thionyl chloride, or dicyclohexylcarbodiimide and N-hydroxysuccinimide, or the like) and reacted with a primary or secondary amine (for example, 5-aminohexanol, pyrrol idone-3-propylamine, or ihe like) to provide the desired anaiog 4. In one variant, a halo-acetophenone can replace bcnzaldehyde 2; the resultant cinnamides 4 are substituted with a methyl group at the 3-position. Alternatively, the order of these coupling steps may be reversed (Scheme 2). A substituted halocinnamic acid S (e.g. 3-chloro-2-nitrocinnamic acid or the like) may he coupled with a primary or secondary amine (e.g. N-acetylpipcrazine OT the like) as described above to give the corresponding amide 6. The halo-group can then be displaced with a substituted thiophenol in the presence of base to provide the product 7. A number of the compounds described herein may be prepared from intermediate benzylic alcohols like 8 (Scheme 3) Activation of the alcohol moiety (for example, using phosphorus tribromide or methanesulfonyl chloride and lithium halide in dimethylformamide) and displacement with a primary or secondary amine (e.g. morpholine. N-formylpiperazine or the like) provides analogs with structures related to 9. Alternatively the alcohol may be oxidized (for example using TPAP or PCC or the like) to give aldehyde lfl. Cinnamides like 13 may be prepared from halo-substituted derivatives 11 by palladium-mediated coupling (e.g. using tetrakis (o-tolyl phosphine) palladium (0), Pd,(dba)„ or the like] with acrylarnidc derivatives 12 (Scheme 4). In similar manner, anilino-cinnamidcs like 16 can be prepared by palladium-mediated coupling of amines 15 with halo-cinnamides 14. In some cases, functional groups on the aromatic rings can be modified to produce new analogs (Scheme 5). For example, a nitro group in compounds like 17 may be reduced [for example, with tin(ll) chloride, or by catalytic hydrogcnation. or the like) to the corresponding amine 18. This amine may then itself be converted to a halogen, for example by diazotization using nitrous acid or t-butyl nitrite in the presence of a metal halide salt like cupric bromide, providing analog 19. It is also possible to assemble cinnamide-stibstituted diary! sulfides in a "reverse" sense (Scheme 6). Thus, for example, compound 20, prepared as described in Scheme 1, may be deprolected by treatment with base (e.g. potassium t-butoxide or the like) to provide thiolatc anion 21, which may be reacted with an activated haloarene (e.g. 2,3-diehlorobenzaldehyde, 3-chioro,4-fluorobenzaldehyde or the like) to provide the corresponding product 22. Alternatively, this same thiolate anion may Decoupled withunactivated aryl hal ides (e.g. aryl bromide or Aryl iodides) using a metal-catalyzed Ullman coupling procedure (for example, using a palladium or nickel catalyst) to give product 23. A further method for producing diarylsulfide cinnamides is shown in Scheme 7, wherein the diaryl sulfide is formed through coupling of a suitably protected aryl thiol 28 to an activated cinnamale ester 27. Substituted phenol 24 may be brominated to give bromophenol 25. Heck-type coupling of bromide 25 with an appropriate olefinic substrate, for example methyl acrylate, is effected with palladium catalysis, leading to the cinnamate ester 26. The phenol is then activated towards further reaction, for example by conversion to the corresponding triflate 27 under standard conditions. The required protected thiol 28 may be prepared by the method of XXX {Tetrahedron Lett. 1994,35. 3221-3224), by coupling an aryl halide or triflate with triisopropylsilyi thiol under palladium catalysis. The two partners 27 and 28 are then reacted in the presence of a fluoride source, for example cesium fluoride, to provide the diarylsulfide cinnamate 29. Hydrolysis is accomplished by basic media, such as lithium or sodium hydroxide in water-THF, and the resulting acid 30 is coupled to amines under standard amide-bond forming conditions (for example, EDC/HOBt) IQ produce the amides 31. A method for preparing cinnamides bearing two a^lthio groups is outlined in Scheme 8. Commercially available difiuoro cinnamic acid 32 was coupled with an amine, using standard conditions, and this derived amide 33 was reacted with excess aryl thiol to provide the bis-sulfide 34. Compounds which contain trifluoromethyl groups on the cinnamide-portion of inhibitors were made by the method shown in Scheme 9. According to the method of XXX (Ref), Diels-Alder reaction between l,I,l,4,4.4-hexafluoro-2-butyne and 2-methylfuran led to bicyclic ether 35, whiuh was rearranged with Lewis acid (for example, baron trifluoridc etherate) to the phenol 36. The methyl group is then converted to the corresponding aldehyde 37 by bromination followed by reaction with dimethylsulfoxide. Using the analogous procedures described for Scheme 1 above, the pheno! was activated and condensed with thiols under basic conditions lo afford diarylsulfide aldehydes 38, and further converted to cinnamides 39 by the previously described procedures. i Cinnamides bearing more complex substituted piperidine amides can be produced by the methods outlined in Scheme 10 and 11. Cinnamic acids 40 are coupled to spiro-hydantoin piperidine 41, and the derived amide 42 is first reacted with an activating reagent (for example di-tert-butyl dicarbonate), and then ! hydrolyzed to the amino acid 43. The derived amino group may then be reacted further, for example with acid anhydrides or acid chlorides, to produce amides 44. Further derivatives of piperidine amides can be obtained by coupling of piperidinone 45 with cinnamic acids 40, as shown in Scheme 11. Standard coupling conditions lead to amide 4fi, which is first reduced to the corresponding alcohol, then hydrolyzed to afford hydroxy acid 47. Also included in this invention are compounds derived from coupling of amines, or amino acid derivatives (such as a-amino esters) to the carboxylic acid group of cinnamides 48, using standard coupling and hydrolysis methods, as outlined in Scheme 12. Thus, amides 49 are produced directly from amine coupling reactions. Amino acid esters are coupled lo 48, and the derived esters are hydrolyzed to the corresponding acids 50. Inhibitors bearing substituted piperazine (or homopiperazinc) cinnamides may be produced by the methods described in Scheme ] 3. The methods described may be utilized to produce piperazine amide 51. Secondary amine 51 then serves as educt for preparing amides 52, through standard coupling reactions. Alternatively, 51 may be converted to tertiary amines 53. through standard reductive alkylation methods (for example, condensation with an aldehyde in the presence of a reducing agent such as sodium triacetoxyborobydride). A process for preparing analogs with amino substitutions of the aryl portion of the sulfides is illustrated in Scheme 14. The intermediate triflate 27 is reacted with halo-substituted thiophenols 54 (X = Dt, CI, OTf. OTs) under basic catalysis, to provide the sulfide derivative 55. The halogen or activated hydroxy! is then substituted with an amine, using the method of Buchwald (Old, D. W.; Wolfe, J. P.; Buchwald, S. L. J. Am. Cheat. Soc. 1998,120. 9722-9723). Similar transition-metal catalyzed reactions may be applied, for example, the method of Hartwiy {Hamann, B. C; Hartwig. J. F. J. Am. Chem. Soc. 1998,120. 7369-7370). The NR3R, group may constitute a cyclic or acyclic group, optionally substituted with additional functionalities that may enhance the activities of the compounds, and that further synthetic transformations familiar to those skilled in the art may he applied. For instance, ester groups may be hydrolyzed to the corresponding carboxylic acids or amides. The derived anilino sulfides may then be processed as described above lo produce the cinnamides 56. EXAMPLES The compounds and processes of the present invention may be better understood in connection wiih ihe following Examples, which are intended as an illustration of and not a limitation upon the scope of the invention. Example 1 (2.4-DichloroDhenvl^2-(E-K&-hy(lr(ixvhe?ivlamino'icarbonvnethenvI'iphcnvl1 sulfide Kxample 1A 2 ■ ( Example IB Example 1C (2.4-Dichiorophenvnf2-(fc"-f(6-hvdroxyhexvlaminn)carhonvl)ethenvhnhenyll sulfide A suspension of the acid (284 mg, 0.87 mmol) from Example IB in 5 mL of methylene chloride was stirred with (COCl)2 (84 u.L, 0.97 mmol). and one drop of DMF under nitrogen atmosphere for 90 minutes. The solvent was then removed under vacuum. The residue (COO), was removed with benzene (2x) in vacuo. To a separate flask, previously filled with 6-amino-l-hexanol (12 mg, 0.10 mmol). Hunig's base (22.8 u.L, 0.13 mmol) and DMAP {1.1 mg, 0.008 mmol) in 2.0 mL of CH2aJt ihe acid chloride (30 mg, 0.087 mmol) in 1.0 mL of CH,C1- was then dropped in slowly. After 30 minutes, the reaction mixture was poured into 3N HC1 and extracted mxb ethyl aceetate (EtOAc). The organic layer was washed with brine, dried widi •Ja,S04, condensed under reduced pressure. The crude product was purified by Example 2 (2.4-Dichlorophenvn[2-f £-(0-n-imidazolvnpropvlarnino)carbonvO elhenv] [phenyl] sulfide The title compound was prepared by the procedures described in Example i C substituting 6-amino-l-bexanol with 1 -{3-aminopropyl)imidazole. White powder; 'H Example 3 (2.4-DichlorQphenvl)[2-chlorn-4-(£-((2-hvdroxvethvlaminokarbonvn ethenvDphenvl | sulfide The title compound was prepared by the procedures described in Example 1 substituting 2-chlorobenzaldehyde wilh 3-ch]oro-4-fluoro-benzadchyde, and 6-amino-1-hexanol with cthanolamine. Colorless oil; 'H NMR (CDC1„ 300 MHz) 5 3.57 (q../ Example 4 f2.4-Piehlorophenvnr2-chbTO-4- ethenvQphenvH sulfide The title compound was prepared by the procedure!; described in Example 1 substituting 2-chlorobenzaldehyde with 3-chloro-4-fluoro-benzadehyde. Colorless oil; Example 5 ethenvl) phenyl! sulfide The title compound was preparea oy ine pruteuures described in Example 5 substituting 2-chlorobenzaldehyde with 3-chloro-4-fluoro-benzadehyde, and 6-amino-l-hexanol with diethanolamine. Colorless oil; 'H NMR (CDCI,, 300 MHz) 5 2.99.(br Example 6 (2,4-Dichlorophenvni2-chloro-4-{C-ff3-n-pvrrolidin-2-onlvlDropvlaminoiearbonvl) ethenvhphenvl [ sulfide The title compound was prepared by the procedures described m Example 1 substituting 2-chlorobenzaldehyde with 3-chloro-4-fluoro-benzadehyde. and 6-amino-1-hexanol with ]-(3-aminopropyl)-2-pynolidinone. Colorless oil; 'HNMRfCDCI,, Example 7 f2.4-DichluroDhenvlir2-chloro-4-(g-carfaonvl>cthenvl^henvll sulfide The title compound was prepared by the procedures described in Example 1 ubstituting 2-chlorobenzaldehyde with 3-chloro-4-fluoro-benzadehyde, and 6-amino--hexanol with morphoiine. White solid; 'H NMR (CDC1„ 300 MHz) 6 3.59-3.80 Oh, Kxample 8 f2.4-Dichlorophenvh[2-chioro-4-( £-f ethenvhphenvl] sulfide Tbe tilte compound wss prepared by the procedures described iit Example 1 ubstituting 2-chlorobenzaldehyde with 3-chloro-4-fluoro-benzadchyde, and 6-aminr,--hexanol with 1-mcthylpiperazine. Colorless oil; 'H NMR (CDC1„ 300 MIL;) S 2.37 Example 9 ethenypphenvn sulfide The title compound was prepared by the procedures described in Example 1 substituting 2-chlorobenzaldehyde with 3-chloro-4-fluoro-benzadehyde, and 6-amino-1-hexanol with 1-acetylpiperazine. White solid; 'H NMR (CDC13. 300 MHz) 5 2.15 Example 10 l,2.4-f)ichlorophenv()f2-chioTo-4-i'it-'-('i'4-f2-pvridvMpiperaz]n-I-vilcarbonvi) ethenvHphenyl) sulfide The title compound was prepared by the procedures described in Example 1 substituting 2-chlorobenzaldehyde with 3-chloro-4-fluoro-benzadehyde, and 6-amino- 1 -hexanol with 1 -(2-pyridyl)piperazine. White solid; 'II NMR 1H), 8.19-8.24 (m, 1H). MS (DCI/NH3) (M+H)4 at mfz 504,506, 508, 510. Analysis calculated for C,4HMN,0,C1,S,: C, 57.10; H, 3.99; N, 8.32. Found: C, 57.12; H, 4.06; N, 8.29. Example ] 1 (2-(HvdroxvmethvDpheny])[2-chloro-4-( E-{{\ -morpholinvltearbonvh ethenvDphenyll sulfide The title compound was prepared by the procedures described in Example 1 substituting 2,4-dichiorothiophenol with 2-mercaptobenzyl alcohol, 2-chlorobenzaldehyde with 3-chloro-4-fluoro-benzadehyde, and 6-amino-l-hexanol with morphoiine. White solid; 'H NMR (CDC1,. 300 MHz) 5 3.50-3.62 (br m, 6H), Example 12 (2-Bromophenyllf2-chlofo-4-f f-tn-morpholinvDcarbonvnethenvnphenvll sulfide The title compound was prepared by the procedures described in Example 1 substituting 2,4-dichlorothiophenol with 2-bromothiophenol, 2-chlorobenzaldehyde with 3-chloro-4-fluoro-benzadehyde, and 6-amino-]-hexanol with moipholine. White solid; 'H NMR (d'-DMSO, 300 MHz) 5 3.50-3.66 (br m, 6H), 3.66-3.79 (brm, 2H), Example 13 2.4-Dichlorophenvn[2-chlorQ-4-f £-((4-f2-hvdroxvethv])pipenKiti-l.-,yl)carbonyl) ethenvltphenvll sulfide The litle compound was prepared by the procedures described in Example 1 ubsliluting 2-chlorobenzaldehyde with 3-chloro-4-fluoro-bcn; Example 14 2.4-Diuhloronhenvn[2-chlQro-4-(£- cthenyHphenvl | sulfide The title compound was prepared by the procedures described in Example 1 substituting 2-chlorobcnzaldehyde with 3-chloro-4-fluoro-benzadehyde, and 6-amino-1-hexanol with l-[2-(2-bydroxyethoxy)ethyl]piperazine. Colorless oil; 'H NMR Example 15 (2-BromonhenvlU2-chloro-4-(£-f(3-fhydroxymethvl)piperidiii-l-vlkarbonvn ethenyhphenvl] sulfide The title compound was prepared by the procedures described in Example 1 substituting 2,4-dichlorothiophenol with 2-bromothiophenol, 2-chiorobenzaldehyde with3-chloro-4-fluoro-benzadehyde. and6-amino-I-hcxancii with 3-hydio^Tfteilti^prperiiime.'H WvTO. (YWISO-V300MHz)&%XH {ix,J=\ll Hz, 1H>. Example 16 (2-Bromophenvl)f2-ch]ori>4-( £-iT2-fhvdroxvmcthvl)piperidin-l-v])carbonvl) ethfittvtlpheiivl] sulfide The title compound was prepared by the procedures described in Example 1 ubstituting 2,4-dichlorothiophenol with 2-bromothiophenol, 2-chl0Tobenzaldehyde with 3-chloro-4-fluoro-benzadehyde, and 6-amino-l-hexanol with 2-,ydroxymethylpiperidine. 'HNMR (DMSO-d,, 300MHz)5 8.03 (m. IH), 7.79 (d, J= Example 17 f2-BromophcnYl)[2-chloro-4-(£'-f(3-aceiamidopvrTolidin-l-vncarbonvl) elhenyl)phenvll sulfide The title compound was prepared by the procedures described in-Example 1 ibstituting 2,4-dichlorothiophenol with 2-bromothiophenol, 2-chlorobenzaldehyde ith 3-chloro-4-fluoro-benzadehyde, and 6-amino-l-hexanol with 3-letamidopyrroHdiiw. 'H NMR (DMSOA. 300MHz) 5 8.14 (m, IH), 8.07 (dd,./ = Example 18 (2-Isopropvlphenvl1f2-triflMoroinethvl-4-f £-i,(2-carbomethoxv-4-(feW- buloxvcarbonvl)pipcra2in-l-vl'lcarbonv])ethenvl1 phenyl] sulfide The title compound was prepared according to ihc procedures of Example 71. Example 96 f2-lsopropvlphenvl)f2-nitro-4-(£-f(3-fpvridine-4-methvlaniinocarbonvn-4-/er/-buloxycarbonvlpiperazin-l-vltearbonylfethenvl) phenyl] sulfide Prepared according to the procedures of Example 71. giving a yeJJow solid. Example 97 -[2-chloro-4(F-ffmomhfi]in-l-vhcarbQnv[lethenvnDhenvl|sulfide Example 97 A 2-Ethox vbenzen ethi ol To 7.82g of ethoxy benzene und 7.41g of tctramethylethylenediamine in 75 tfi ether, cooled in an ice bath, a solution of 25.6 ml of a 2.5 M n-bulyllithium solution in hexane, was added dropwisc under a nitrogen atmosphere. The mixture was stirred for 1 hour at room temperature and then cooled to -65 degrees. Sulfur (2.28 g) was added in portions. The mixture was stirred for 3 hours at room temperature and Ihcri cooled in ice. LiAlH, (0.6 g) was added and the mixture was stirred 1 hour at room temperature. The mixture was again cooled in ice while 5 ml water was added dropwise followed by 15% HC1 in water until all salts. The aqueous phase was separated and washed with ether. The combined ether layers was washed with HC1, then water. After drying with Na,SO„ the ether was evaporated to give 9.66 g of product. NMR analysis showed 70% pure material with 30%ofadiaryl sulfide impurity. This mixture was carried forward to the next step. Example 97B (2-EthoxvphenvlV[2-chtoro-4fE-ffmorpholin-l-vl'k:arbonvl1ethenvl1nhenvl1sulfide The title compound was prepared according to the procedures of Example 1, substituting the thiol of Example 97 A, giving a white solid, m.p. 12S-127C. 'H NMR Example 98 (2-MethoxyphcnvI)[2-nitro-4-f £-((4-acetvlpJperazin-l - vl karbo nvnelh en vilphen y Hsu I fi de The title compound was prepared by the procedures described in Example S3 substituting 3,4-dimethylthiophenol with 2-methoxythiophenol. giving a yellow solid Example 99 f2-(Azetidin-l-vhphenvn[2-trifluoromethvl-4-(f£-{f4-ffgrf-butoxvcarbonvnninerazifl: 1-yl)carbonYltethcnvn phenvll sulfide The title compound was prepared by the procedures described in Example 69 substituting pyrrolidine with azctidine hydrochloride, and the bromide from Example 12 with bromide from Example 90, giving a white solid. 'H NMR (CDClj, 300 MHz) 6 1.48 (s, 9H), 2.18 (pentet, J= 7.43 Hz, 2H), 3.40-3.53 (m, 4H), 3.53-3.77 (m, 4H), Example 100 {2-fPiperidin-]-vnphenvlM2-trifluorQmcthvl-4- 1-vlkarborwPethenvh phenvll sulfide The title compound was prepared by the procedures described in Example 69 substituting pyrrolidine with piperidine, and the bromide from Example 12 with bromide from Example 90, and isolated as a white solid. 'H NMR (CDC],. 300 MHz) Example 101 0-Chloro-2-formvlpherwl)(2-ch]oro-4-( ff- ethenvli phenyl] sulfide The title compound was prepared by the procedures described in Example 6SB substituting 2,3-dichlorQr*n7.aldehyde with 2,6-dicrilorobertzaldebyde, isolated as a while solid. 'H NMR (CDC1,, 300 MHz) S 2.05 (s, 3H), 3.56 (br s, 2H), 3.61-3.86 (m, Example 102 f2-TrifluoromethvIphenvD[2-trifluoromethyl-4-f ff-W-acetvlpiperazin-l-vllcarbonvl) ethenvh phenyl! sulfide The title compound was prepared according to the procedures of Example 1. Example 103 G-BromophenvDf2-trifluoromethvI-4-i'g-(f4-acety]piperazin-1-vncarbonvn ethenvli phenyl? sulfide The title compound was prepared according lo the procedures of Example 1. Example 104 (3.5-DimethvlphenvM2-trif]uoromethvl-4-( g-fi^-acetvlpiperazin-l-vlkarbonYn cthcnvlt phenyl] sulfide The title compound was prepared according to the procedures of Example 1. lIINMR(CDCl.„300MHz)67.79(s, 1H). 7.64(d, 1H,J= 15.1 Hz), Example 105 l'2-lsopropvlpherivn[2-nitro-4-(£-(l,3-dimethvlaminocarbonvl-4-fpvridine-4-carbonvnpiperazin-l-vOcarbonvl)eiheriYl) phenyl] sulfide Prepared according to the procedures of Example 71, giving a yellow solid. Example 106 (2-IsopropvlDhenvl>f2-mtro-4-f E-((3-dimethvlaminocarbonvl-4-carbomettioxvpiperaan-1-vlkarbonvhethenvll phenyl] sulfide Prepared according to the procedures of Example 71, giving a yellow solid. Example 107 (2-lsoTgypvtpherwh[2-nitTO-4-( £-((3-dimethyla[ninocarbonvl-4-acctvlnipcra7.m-l-vDcarbonvllethcnvl) phenyl] sulfide Prepared according to the procedures of Example 71. giving a yellow solid. Example 108 (2-Isopropvlphenvllf2-nitro-4-( g-ff3-n-morpholinocarbonvD-4-«r/- butoxvcarhonvlpiperazin-l-vhcarbonvltethenvl^ phenyl] sulfide Prepared according to the procedures of Example 71, giving a yellow solid. Example 109 (,2-lsopropvlphenvlU2-nitro-4-(£-ff3-(pvridine-4-rnethvlarriiriocarborivnpiperazin-l-vlicarbonvlleihenvh phenvl) sulfide Prepared according to the procedures of Example 71, giving a yellow solid. Example 110 (l-IsoptopvlpheOTntl-nitro-A-fE-CtO-dimethvlaminociirbonvUpiDerazin-i-vOcarbonvnethenvl} phenvll sulfide Prepared according to the procedures of Example 71, giving a yellow solid. Example 111 (2-Isot>ropvlphenvni2-nitro-4-(£-(r3-fben7.vlaiTiinocarbonvn-4-/gr/-butoxvcarbonvlpiperazin-1-vlkarbonvDethenv]') phenyl! sulfide Prepared according to the procedures of Example 71, giving a yellow solid. Example 112 (2-IsopropvlphenvP|'2-nitro-4-( E-((3-fdimethvlaminocarbonvl')-4-/err- butoxvcarbonvlpiperazin-l-vncarbonvnethenvn phenyl! sulfide Prepared according to the procedures of Example 71, giving a yellow solid. Example 113 f2-BromophenvPf2-chloro-4-rE-(Y 3-fS,S'-hvdroxvmethvl-pyrrolidin-2-on-1 -yHprop-1 -vlaminokarbonvncthenypphenvllsulfide (2-Bromophenyl)[2-chloro-4-(2-carboxy-E-cthenyl) phenyljsulfide was prepared by the procedures described in Example 1 substituting 2,4 dichlorothiophenol with 2-bromothiophenoJ, 2-chlorobenzaldehyde with 3,4 dichlorobenzaldehyde. l-(3-aminopropyl)-5-((thexyldimethylsilyloxymethyl)-2- pyrrolidinone (0.2818g, 0.8959 mmol) was added to a solution of this cinnamic acid (0.3312g, 0.8959 mmol), l-[3-(dimethylamino)propyl]-3-ethyl carbodiimidc hydrochloride (0.3435g, 1.79 mmol), and 1-hydroxybenzotriazole hydrate (0.1816g, 1.34 mmol) in DMF (4.0 mL). After stirring for 12h the reaction mixture was diluted with EtOAc (250 ml.), extracted with sat. NH.,C1 (1x75 mL), extracted with H,0 (2x75 mL), rinsed with brine (75mL), and dried over Na,SO.,. The resultant thexyldimethylsilyl alcohol was purified by flash chromatography (EtOAc) on silica gel (.4974 g, 83%). Tetrabutylammonium fluoride (.68 mL of 1.0 M solution in THF) was added dropwise to a solution of this protected alcohol (0.4544 g, 0.682 mmol) in THF (1.7 mL). After 2h the reaction was diluted with EtOAc (50 mL) and extracted with sat. NH4C1 (1x25 mL), extracted with H,0 (2x25 mL), rinsed with brine (25mL), and dried over Na,S04. Flash chromatography (EtOAc -> 9:1 CH,Cl,:McOH) on silica gel yielded the title compound (.3144g, 88%). 'H-NMR (DMSO-d*, 300MHz) 5 8.14 (t, J= 5.5 Hz, 1H), 7.81 (m, 2H), 7.53 (dd, J= 8.3.1.7 Hz, 1H), 7.44 (dt, J = 7.7, 1.5, 1H), 7.40 (dU= 7.7,1.8,1H), 7.39 (d,7= 15.6 Hz, 1H), 7.28 (dd,J = 7.7,1.8 Example 114 » f2-Bromophenvnr2-chloro-4-fE-rf3-(pvrroltdin-2-on-l-vl')prop-l.vlaniino')carbonvn cthenvltohenvl'lsulfide The title compound was prepared by the procedures described in Example 1 substituting 2,4 dichlorothiophenol with 2-bromothiophenol, 2-chlorobenzaldchyde with 3,4 dichlorobenzaldehyde. and 6-amino-l-hexanol with l-(3-aminopropyl)- 2-pyrrolidinone. 'H-NMR (DMSO-d,,, 300MHz) 5 8.12 (t, J = 5.9 Hz, 1H), 7.81 (m, Example 115 (2-Bromophenvlir2-chloro-4-(E-(N-methvl-N-(3-fpyrTolidin-2-on-l-vhprop-l-vnaminokarbonvDethenvDphenvnsulfide The title compound was prepared by the procedures described in Example 1 substituting 2,4 dichlorothiophenol with 2-bromothiophenol, 2-chlorobenzaldehyde with 3,4 dichlorobenzaldehyde, and 6-amino-l-hexanol with l-(3- methylaminopropyl)-2-pyirolidinone. 'H-NMR (DMSO-d6,300MHz) 5 8.06 (d, J = Example 116 f2-[2-Methoxvlethoxvphenvn-f2-ch]oro-4rE-rfmorpholin-l-vlkarbonvnethenvllphenvll sulfide The title compound was prepared according to the procedures of Example 97, substituting 2-methoxyethoxybenzene, giving a white solid. 'IINMR (CDCl,, 300 Example 117 (2-IsopropvlphenvD[2-nitro-4-( E-((3-(morpholinocarbonvnDiperazin-1- vltearbonvllcthenvB phenvll sulfide Prepared according to the procedures of Example 71, giving a yellow solid. Example 118 (2-lsopropvIphenvPf 2-nitro-4-( £-((4-/er/-butoxvcarbonvlpiperazin-1 - vl)carbonvl)ethenvl) phenvll sulfide Prepared according to the procedures of Example 71, giving a yellow solid. Example 119 (2-Isopronvlnhenvl)[2-nitro-4-( E-((4-methoxvcarbonylpiperazin-l-vncarbonyPethenvP phenvll sulfide Prepared according to the procedures of Example 7]. giving a yellow solid. Example 120 (2-Isopropvlphenvn[2-nitro-4-f £-(4-(pvridine-4-carbonvl)piperazin-l- vncarbonvllethenvl) phenyl! sulfide Prepared according to the procedures of Example 71, giving a yellow solid. Example 121 (2-lsopropvlphenvlX2-nitro-4-(£-fG-(pvridine-3-methvlaminocarbonvn-4-re/7- butoxvcarbonvlpiperazin-l-vl')carbonvPethenvl) phenvll sulfide Yellow solid; 'H NMR (DMSO-d6? 300MHz)5 1.14 (d. J = 6.8 Hz. 611); 1.31-1.46 (br Example 122 f2-Isopropvlphenvl')f2-nitro-4-(£-(G-(pvridine-2-methvlaminocarbonvnpiperazin-l- yDcarbonvDethenvO phenvll sulfide Prepared according to the procedures of Example 71, giving a yellow solid. Example 123 (2-Isopropvlphenvl'ir2-nitro-4-(£'-(,(3-(pvridine-3-methvlaminocarbonvht>iperazin-l-vDcarbonvllethenvD phenyl! sulfide Prepared according to the procedures of Example 71, giving a yellow solid. 'H Example 124 (4-Hvdroxvphenvl)f2-nitro-4-( £-((4-acetvlpiperazin-1 - vllcarbonvltethenvnphenvllsulfide The title compound was prepared by the procedures described in Example 83 substituting 3,4-dimethylthiophenol with 4-hydroxythiophenol. Yellow solid (23 mg, (2-Bromophenvl)f2-chloro-4-f E-(f4-hvdroxvpiperidin-l-vl1carbonv]) eihenvllphenvll sulfide The title compound was prepared by the procedures described in Example 1 substituting 2,4-dichlorothiophenol with 2-bromothiophenol, 2-chlorobenzaldehyde with 3-chloro-4-f]uoro-benzadehyde, and 6-amino-l-hexanol with 4-hydroxypiperidine. 'H NMR(DMSO-d6,300MHz) 6 8.08 (d, J= 1.7 Hz, 1H), 7.80 Exampie 19 (2-Bromopbenvl)[2-chloro-4-f g-((piperidin-l-yncarbonvn ethenvllphenvll sulfide The title compound was prepared by the procedures described in Example 1 substituting 2,4-dichlorothtophenol with 2-bromothiophenol, 2-chlorobenzaldehyde with 3-chloro-4-fluoro-benzadehyde, and 6-amino-l-hexanol with piperidine. '11 NMR (DMSO-d6, 300MHz) 6 8.08 (d,J= 1.7 Hz, 1H), 7.80 (dd,J= 8.1.1.4 Hz. 1H), Example 20 (2.4-DichlQrophenvhl2-chloro-4-f £-ff3-carboxvpiperidm-l-vlicarbonvn ethenvllphenvll sulfide The title compound Was prepared by the procedures described in Example 1 substituting 2-chlorobenzaldehyde with 3-chloro-4-fluorQ-benzadehydc, and 6-amino-1-hcxanol with nipecotic acid. Colorless oil; 'H NMR (CDC1,, 300 MHz) 5 1.44-1.68 (brm, IH), 1.68-2.00(brm,2H),2.51-2.67(brm, 1H), 3.13-3.37 (brra, IH), 3.80- Hxample 21 (2.4-Dichlorophenvnf2-chloro-4-( g-((4-carboxvpiperidin-I-ylkarbonvl> ethenvllphenvll sulfide The title compound was prepared by the procedures described in Example I substituting 2-chlorobenzaldehyde with 3-chloro-4-fluoro-benzadehyde, and 6-amino-1 -hexanol with isonipecotic acid. Colorless oil; 'H NMR (CDC).,. 300 MHz) S 1.68- Example 22 C2-Bromophenvl'ir2-chloro-4-f £-f(4-aceiylhomopiperaan-1-vhcarbony]ethenvhphenvll sulfide The title compound was prepared by the procedures described in Example 1 substituting 2,4-dichlorothiophenol with 2-bromoihiopnenol, 2-chlorobenzaldehyde with 3-chloro-4-fluoro-benzadebyde, and 6-amino-l -hexanol with 4-acetylhomopiperazine. 'H NMR(DMSO-d6, 300MHz)8 8.10 (m, 1H), 7.81 (d, J= Example 23 (2-BromoDhenvn[2-chloro-4-f £-ffthiomorpholin-l-vltearbonvl)ethenvl1phenvl| sulfide Tlie title compound was prepared by che procedures described in Example 1 substituting 2,4-dichlorothiophenol with 2-bromothiophenol. 2-chlorobenzaldehyde with 3-chloro^-fluoio-benzadehyde, and 6-amino-l-hexanol with thiomorpholine. 'H Example 24 fl-Bromophenynp-ctiloro^-ff^-n-benzimitla^ol^-onlvipiperidiri-l-vncarbonvl) ethejiy])pheny]) sulfide The title compound was prepared by the procedures described in Example 1 substituting 2.4-dichlorothiophenol with 2-bromothiophenol. 2-chlorobenzaldebyde with 3-ch[oro-4-fIuoro-benzadehyde, and 6-amino-I-hexanol with 4-(I-benzimidazol-2-only)piperidine. 'HNMR(DMSO-ds. 300MHz) S 8.14 (d,7= 1.5 Hz, IH), 7.80 Example 25 f2-Broropphenvn(2-chli>ro-4-( E- ethenvhphenyll sulfide 'JTie title compound was prepared by the procedures described in Example 1 substituting 2,4-dichloioihiophenol with 2-bromoihiophenol, 2-chlorobenzaldchyde with 3-chloro-4-fluoro-benzadehyde, and 6-amino-l-hexanol with tetrahydroisoquinolinc. 'H NMR (DMSO-d«, 300MHz) 5 8.12 (d,J= 7.4 Hz, 1H), Example 26 (2-Mcthvlphenvl1f2-triflLinn)meihvl-4-f £-f(4-acetvlpiperazin-1-vhcarbonvi) ethenyDphenvl] sulfide The title compound was prepared by the procedures described in Example 1 substituting 2,4-dichlorothiophenol with 2-methylthiophenol. 2-clilorobenzaldehyde with 4-fluoro-3-trifluoromethylbenzadchyde. and 6-amino-l-hexanoI with 1-acetylpiperazine. 'H NMR (CDC1,. 300MHz) 5 7.79 (s, 1H); 7.63 (d, J = 15.4Hz. Example 27 f2-Melhvlphenvlir2-trifluoromethvl-4-|'£-in-morpholinvl)carbonvl) cthenvl)phenyll sulfide The title compound was prepared by the procedures described in Example 1 substituting 2,4-dichlorothiophenoI with 2-methylthiophenol, 2-chlorobenzaldehyde with 4-fluoro-3-trifluoromethylbenzadehyde, and 6-amino-l-hexanol with Example 28 (2-Methvlphenyl)[2-trifluoromethvl-4-( E-((2-( 1 -morpholinvnethvlamino)carborivl) ethenvllphenvH sulfide The title compound was prepared by the procedures described in Example 1 substituting 2,4-dichlorothiophenol with 2-me!hyIihiophenol. 2-chlorobenzaldehyde with 4-fl uoro-3-trifluoro methyl be nzadehyde. and 6-amino-1 -hexanol with 2-(l -morpholinyl)ethylamine. lH NMR (CDC1„ 3()0MHz> S 7.80 (s, 1H); 7.56 (d. J - 15.8 Example 29 f2-MethvlphenvlU2-trifluoromethvl-4-f E-((4-phenv)piperazm-l-vhcarbonvl) ethenyDphenyll sulfide The title compound was prepared by the procedures described in Example 1 substituting 2,4-dichlorothtophenol with 2-methylthiophenol, 2-chlorobenzaldehyde with 4-fluoro-3-trifluoromcthylbenzadehyde, and 6-amino-l-hexanol with 4-phenylpiperazine. lH NMR (CDCi3, 300MHz) S 7.81 (s, 1H); 7.64 (d, J = 16.0 Hz, Example 30 (2-Methvlphenvn[2-trifluoromelhvl-4-( £-f{3-(l-pyrTolidin-2-onl vtpropv 1 ami n o )c arbon vl) ethenvOphenvl] sulfide The title compound was prepared by the procedures described in Example 1 substituting 2,4-dichiorothiophenol with 2-methylthiophenol, 2-chlorobenzaldehyde with 4-fluoro-3-trifluoromeihylbenzadehyde, and 6-amino-l-hexanol with 1-pyrrolidin-2-only)propylamine. 'H NMR (CDCI,, 300MHz) 5 7.78 (s, 1H); 7.53 (d, J Example 31 (2-Methvlphenv])f2-trifluoromethvl-4-f E-ffcvcloDropvlaminotcarbonYl) ethenvhphenvll sulfide The title compound was prepared by the procedures described in Example 1 substituting 2,4-dichlorothiophenol with 2-methyltbiophenol, 2-chlorobenzaldehyde with 4-fluoro-3-trifluoromethylbenzadehyde. and 6-amino-l-hexanol with cyclopropylamine. 'H NMRfCDCI,. 300MHz) 5 7.76 (s, 1H); 7.56 (d, J = 15.4 Hz, Example 32 (2.4-Dichlorophenvn[2-nitro-4-f f-174-acetvlpiperazin-l-vHcarhonvh ethenvltphenvll sulfide Example 32A l-Chloro-2-nitrQ-4-( £-((4-acetvlpiperazin-1-vl)carbonyl>elhenvh benzene To a stirred solution of/7wiJ-4-chloro-3-mtrocinnamic acid (1.50 g, 6.59 mmol) and 1-acetyipiperazine (0.89 g, 6.94 mmol) in 20 mL of DMFat room temperature was added EDAC (1.4 g, 7.30 mmol). The mixture was then stirred at room temperature for 2 hours. TLC indicated the complete consumption of the acid. Water was then added to quench the reaction and to precipitate out the product. Cinnamide was then collected through filtration and washed with cold water. The light yellow product was dried in vacuum oven overnight at 40 °C to give 2.04 g (6.03 mmol. 91.6 %) of the title compound. Example 32B l'2.4-Dichlorophenvn[2-nitrc-4-('£'-(f4-acetvlpiperazin-l-vl'icarbonvl) ethenvUphenvll sulfide To a stirred solution of 4-chloro-3-nitro-cinnamidc (275 mg, 0.814 mmol) from Example 32A in 1.0 mLof DMF was added potassium carbonate (169 mg. 1.22 mmol), followed by the diopwise addition of 2,4-dichlorothiophenol (146 mg. 0.815 mmol). The mixture was then stirred at room temperature for 60 minutes. Completion of the reaction was indicated by the TLC. Water was then added to precipitate the product. Filtration, washing with cold water, and drying in a vacuum oven afforded 350 mg (0.728 mmol, 89%) of the titled compound as light yellow solid. 'HNMR (d6-DMSO, 300 MHz) 5 2.05 (s, 3H), 3.42-3.50 , Example 33 (2,4-Dichlorophenvn[2-nJtTo-4-i'g-(G-n-DVfTolidin-2-Qn]iy)Rp)pYlaniinotcarbonvl) etftenvhphenvl] sulfide The title compound was prepared by the procedures described in Example 32 substituting 1 -acetylpiperazine with I-(3-aminopropyl)-2-pyrrolidinone. Light-yellow powder; 'H NMR (d6-DMSO, 300 MHz) 5 1.64 (p, ./= 7.1 Hz. 211). 1.91 (p, J= 7.5 Example 34 (2.3-Dichlorophenvl)[2-nilTO-4-(£-((4-acetvlpipcrazin-l-vl1carbonvh ethenvhphenvll sulfide The title compound was prepared by the procedures described in Example 32B substituting 2,4-dichloroihiophenol with 2,3-dfchlorothiophenol. Light-yellow powder; 'H NMR (d'-DMSO. 300 MHz) 8 2.04 (s. 3H), 3.42-3.50 (br m, 4H), 3.50- Example 35 (4-Bromophenvll[2-nitro-4-i' £-(f4-acety1piperazin-1-vlkarfonv0ethenvl)phcnvil sulfide The title compound was prepared by the procedures described in Example 32 ubstitucing2,4-dichlorothiophenol with4-bromothiophenol. Light-yellow powder; 'H JMR (d*-DMSO, 300 MHz) S 2.04 (s, 3H), 3.47 (br m, 4H). 3.52 (br m, 1H), 3.60 (br Example 36 sulfide The title compound was prepared by the procedures described in Example 32 iibsiituting 2,4-dichlorothiophenol with/Hhiocresol. Light-yellow powder; 'H NMR i6-DMSO, 300 MHz) 5 2.04 (s, 3H), 2.39 (s, 3H). 3.47 (br m. 4H). 3.52 (br m, 1H), Example 37 (2,4-Dichlorophenvnf2-nilro-4-f £-pipera?in-]-vHcarbonYD ethenvDphenvl] sulfide The title compound was prepared by the procedures described in Example 32 substituting 1 -acetylpiperazitic with wr/-butyl piperazine carboxylate. Light-yellow powder; 'H NMR (d'-DMSO, 300 MHz) 5 1.42 (s, 9H), 3.36 (overlapping m, 4H), Example 38 (2.4-Dichlorophenvl)[2-nitro-4-{£-f(4-(2-fiirovkarbonvl)piperazin-i-yllcarbonvn ethenvDphenvH sulfide Example 3SA (2.4-DicriloroDhenvnr2-nitro-4-f£-ffpiperazin-l-vl'lcarbonvnethenvllphcnyll sulfide Trifluoroacedc Acid Salt The compound (100 rug, 0.186 mmol) from Example 37 was dissolved in 0.5 ml. of neat trifluoroacctic acid (TEA). The mixture was stirred at room temperature for 1 hour. The TFA was then removed under vacuum to give the title compound (105 mg) as a yellow solid. Example 38B f2,4-Dichlorophenvnr2-nitro-4-(£'-f(4-(2-furovlcarbonvl')piriera2in-l-vl)carbonvl) ■ e then vl) phenyl) sulfide To a stirred solution of piperazine TFA salt (35 mg. 0.067 mmol) from Example 38A in 2.0 mL of CHX1, was added Et,N (23 p.L, 0.17 mmol), 4-dimethylaminopyridine (DMAP) (1.0 mg, 0.0082 mmol), and furyl chloride (8.0 y.L, 0.080 mmol). The mixture was then stirred at room temperature for 30 minutes before the solvent was removed. The crude product was purified with GUson HPLC system, YMCC-18 column, 75x30 mm 1.D..S-5 uM, 120 A, and a flow rate of 25 mL/mm, K=2 14.245 nm; mobile phase A, 0.05 M NH40ac. and B, CH,CN; linear gradient 20-100% of B in 20 minutes to give the title compound (24 mg, 67%) as light-yellow powder; 'H NMR (d6-DMSO, 300 MHz) 5 3.62-3.87 (br m. 8H), 6.66 (q, J= 2.1 Hz, Example 39 f2,4-Dichlorophenvnf2-nnro-4-f £'-((4-fmcihanesulfonvi)piperazin-l-vikarbonvl) ethenvDphenvIl sulfide The title compound was prepared by the procedures described in Example 38B substituting furoyl chloride with methanesulfonyl chloride. Light-yellow powder; 'H NMR (d6-DMSO, 300 MHz) 8 2.90 (s. 3H), 3.25 (br m, 4H), 3.68 (br m, 211), 3.83 (br Example 40 l,2.4-Dichlorophenvi)f2-nitro^t-f £-f (4-fdiethvlamino carbon vlmethv Dpi perazin-l- vncarbonvh ethenvhphenvll sulfide The title compound was prepared by the procedures described in Example 38B substituting furoyl chloride with 2-chloro-.V,AF-diethylacetamide. Light-yellow powder; 'H NMR (d6-DMSO, 300 MHz) 5 1.01 (t, J = 7.2 H^, 3H). 1.13 {:. J = 7.2 Hz, Example 4 (214-DichlorophenvI)[2-nirro-4-f £-f(4-fdiethvlaminocarbonvDpincraziri-i- vltcarbonvll ethenvhphenvll sulfide The title compound was prepared by the procedures described in Example 38B substituting furoyl chloride with Mtf-diethyicarbamyl chloride. Light-yellow powder; 'H NMR (d6-DMSO, 300 MHz) 5 1.06 (t, J= 6.9 Hz, 6H), 3.12 (br m, 4H), 3.15 (q, J Example 42 (2.4-Dichlorophenvl1[2-niiro-4-('£- carbonv he thenvll phenyl! sulfide The title compound was prepared by the procedures described in Example 38B substituting CH,CI._, with CH,CN as solvent, and furoyl chloride with lerf-butyl bTomoacetate. Light-yellow powder; 'H NMR (CDC1,. 300 MHz) 8 1.47 (s, 9H), 2.70 Example 43 C2.4-Dkhlorophenvi1[2-nitro-4-f £-((4-(carhoxvcarbonvl)piperazin-l-vl)carbonvl) ethenvDphenvl] sulfide Example 43 A (2,4-Dichloropheny])f2-nitri>-4-( £-C(4-(carbeihoxvcarbonvnpiperazin-l-vl'icarbonvil 1 ethcnvDphcnvl] sulfide The title compound was prepared by the procedures described in Example 3SB substituting furoyl chloride with ethyl oxalyl chloride. Example 43 B (2.4-Dichlorophenvnr2-nitro-4-{'fcV(4-(carboxvcarbonvnpipcrazin-l-vncarbQnvl) ethenviiphenvll sulfide To a stirred solution of the ethyl ester (40 mg, 0.074 mmol) from-Example 43A in 2 ml, of ethanol was added saturated LiOH (0.25 mL). The mixture was then stirred at room temperature for 2 hours. Water (2 mL) was then added to the reaction mixture, which was then acidified to pH = 2 with concentrated HC1. The precipitates were collected through filtration, washed with cold water, dried under vacuum to give the titled compound (30 mg, 79%) as light yellow solid. 'H NMR (d6-DMSO. 300 MHz)5 3.52 (brm, 4H),3.62 (br m, 2H). 3.76 (br m, 2H), 6.84 (d, J= 9.0 Hz, 1H), Example 44 (-2.4-DichlQrophenvl)r2-nitro-4-l'£-Jf4-(carboxvniethvhpiperaziii-1-vlkarbonv]"l ethenvllphenvl] sulfide The title compound was prepared by the procedures described in Example 38A substituting compound from Example 37 with compound from Example 42. Light-yellow powder; 'H NMR (d6-DMSO, 300 MHz) 5 3.14 (s, 2H), 3.40 (overlapping br Example 45 f2-Mcthvrohenvn[2-nitro-4-l £-((4-acetvlpiperazin-l -vllcarbonvD ethenvnphenyl | sulfide The title compound was prepared by the procedures described in Example 32 substituting 2,4-dichlorothiophenol with o-thiocresol. Light-yellow powder; 'H NMR Example 46 f2-Chlorophenvn[2-niiro-4-f fi-«4-acetvlpiperazin-l-vnc3rbonvncthenvl,iphenvll sulfide The title compound was prepared by the procedures described in Example 32 substituting 2,4-dichlorothiophenol with 2-chlorothiophenol. Light-yeilow powder; 'H NMR (d'-DMSO, 300 MHz) 5 2.04 (s, 3H), 3-47 (br m, 4H>, 3.52 (br m, 1H), 3.60 (br Example 47 (2-Aminophenvn[2-nitro-4-(£-((4-acetvlpiperazin-l-vncarbonvl>ethenvhphenvll sulfide The title compound was prepared by the procedures described in Example 32 substituting 2,4-dichlorothiophenol with 2-aminolhiophenol. Light-yellow powder; 'H Example 48 C2-Hvdroxvmethvlphenvl)[2-niiro-4-(£-ff4-accivlDiDeraaii-l-vl)carbonvn ' eihenvhphenvll sulfide The title compound was prepared by the procedures described in Example 32 substituting 2,4-dichlorothiophenol with 2-mercaptobenzyl alcohol. Light-yellow powder; lH NMR (d6-DMSO, 300 MHz) S 2.03 Example 49 (2-Ethvlphenvnf2-nitro-4-(£-l'(4-acetvlpiperazin-l-vl'>carbonvl)ethenvl)phenvl1 sulfide The title compound was prepared by the procedures described in Example 32 substituting 2,4-dichlorothiophenol with 2-ethytthiophenol. Light-yellow powder; 'H Fxamplc 50 (2-/Jo-ProuvlDhenylH2-nitn>-4-( ff-fM-acetvlpiperazin-l-vncarbonvl^ ethenvliphenvl] sulfide The title compound was prepared by the procedures described in Example 32 substituting 2,4-dichlorothiophenol with 2-isopropylthiophenol. Light-yellow powder; Example 51 (2-/er/-Butvlphenvn('2-nitro-4-f g-f(4-acetvlpiperazin-l-vlkarbonvll ethenvllphenvll sulfide The title compound was prepared by the procedures described in Example 32 substituting 2,4-dichlorothiophenol with 2-ferf-butylthiophenol- Light-yellow powder; 'H NMR (d'-DMSO, 300 MHz) 8 1.46 {s. 9H), 2.04 (s, 3H), 3.47 (br m, 4H). 3.52 (br Example 52 (2 -Chi orophen vl ^ [2-ch ioro-4-f £-(f4 -ac etv Ipi perazi n - 3.-vl tearbon vi)) 2-oropenvnpheiivll sulfide Example 52A 3'-Chloro-4'-[(2-chlorophenvnthiolacetophenone The title compound was prepared by the procedures described in Example 1A substituting 2,4-dichlorothiophenol with 2-chlorothiophcnol, and 2-ehlorobenzaldehyde with 4'-nuoro-3'-chloroacetophenone. Example 52B (2-Chlorophenvn[2-chloro-4-f g-H-ethoxvcarbonyl) 2-propenvllphenvll sulfide To a stirred suspension of NaH (60% in mineral oil, 121 mg, 3.03 mmpl) in 20 mL of anhydrous THF under nitrogen atmosphere was added tricihyl phosphonoacetate dropwisc. After 20 minutes, the acetophenone (600 mg. 2.02 mmol) from Example 52A in THF (5 mL) was added in one portion. The resulting clear solution was then stirred at room temperature for 7 hours. Reaction was then stopped, most of the solvent was evaporated, and the residue was partitioned between EtOAc (2x20 mL) and water. The combined organic layer was washed with water and brine, dried over Na,SO«, concentrated in vacuo. The crude product was purified using silica gel flash column chromatography etuting with 5-10% Et,0 in hexancs to give the (£)-isomer of the cinnamate (500 mg, 68%) as a white solid. Example 52C r?.ChlororjhenvlH2-chloro-4-t g-H-carboxv) 2-propenvnphenvll sulfide A mixture of the cinnamate (500 mg. 1.37 mmol) from Example 52B in 5 mL of EtOH/THF (4:1) was stirred with sal. LiOH solution (0.50 mL) at 50 °C for 2 hours. The mixture was then acidified with 3N HC1 and extracted with CH,CU (3x10 mL). The combined organic layer was dried over MgSOj, concentrated under reduced pressure to give the titled compound (450mg, 97%) as a white solid. Example 52D £?-Chlorophenvh[2-chloro-4-f E-((4-acrtvipiperazin-l-yl)carbonyl)) 2-propenvlmhenyll sulfide The title compound was prepared using the cinnamic acid from Example 52C by the procedures described in Example 1C substituting 6-amino-l-hexanol with 1-acetylpiperazine. White solid; 'H NMR (CDCI3,300 MHz) 8 2.10-2.20 (m. 3H), 2.25 (s, 3H), 3.40-3.80 (m, 8H), 6.28 (s, III), 7.00 (d, J= 8.7 Hz. 1H). 7.19-7.36 (m. 4H), 7.46-7.56 (m, 2H). MS (APCI) (M+NH4)* at m/z 466,468,470. axampie 3J (2-n-Mc>Tphnlinvlmethvliphenvn[2-ch]oro-4-f f■((!-morpholinvllcarbonvll ethenvh phenyl! sulfide Example 53 A (2-( 1 -Rromomethvllphenyhf 2-chloro-4-( F-f( 1 -morpholinvltearbonvl) ethenvH phenvll sulfide To a stirred solution of benzyl alcohol (195 mg, 0.32 mmol)from Example ll in 2.0 mL of anhydrous DMF was added LiBr (48 mg, 0.35 mmol). The mixture was then cooled in an ice-water bath, and PBr3 (60 uL, 0.40 mmol) was dropped in slowly. The ice bath was then removed and the mixture was stirred at room temperature for 1 hour. Water was then added, the mixture was then partitioned between EtOAc and aqueous NaHCOj. The aqueous layer was extracted with EtOAc onte. The combined organic layer was washed with water and brine, dried over Na,SO„ concentrated on a rotavap. The crude bromide (230mg) was used directly for the aJkylation without purification. Example 53R (2-( 1 -Mnrpho1invlmcthvl)phenvnf2-ch1oro-4-( E-fn-moraholinvOcarbony]) ethenvH phenvll sulfide To a stirred solution ofmorphoh'ne (10 uL, 0.11 mmol) in 0.5 mL of CH,CN was added Hunig's base (23.7 uL, 0.14 mmol), followed by the bromide (40 mg. 0.091 ramol). The mixture was then stirred at room temperature for 2 hours. Solvent was then removed and the crude product was purified with Gilson Preparative HPLC as described in Example 38B to give the tilled compound as a white solid. 'H NMR (d6-DMSO, 300 MHz) 8 2.33 (br t, 4H), 3.45 (br t, 4H), 3.50-3.65 (m, 6H), 3.56 (s. Example 54 (2-(4-( 1.j-Beny.odioxolvl-5-rnethvnpiperazin-l -vimethvl)phcnvn;2-chioro-4-f E-(( 1 -morphoiinvDcarbonvn ethenypphenvll sulfide Tl>c title compound was prepared by the procedures described m Example 53B substituting morpholine with 1-piperonylpiperazine. White solid; 'H NMR (d'- Examplc 55 f2-f4- morpholinvltoarbonvll ethcnvPphenvll sulfide The title compound was prepared by the procedures described in Example 53B substituting morpboline with Ar-isopropyl-l-piperazineacetamide. White solid; 'H Example 56 (2-fW-Etboxvcarbonvlmeihvl-A^-melhvl)aminomethvltohenvn[2-chloro-4-f E-((\- rtiorDholinvDcarhonvll ethenvllphenyl] sulfide The title compound was prepared by the procedures described in Example 53B substituting morpholine with ethyl sarcosinate hydrochloride. White solid: 'IINMR Example 57 f2-Formvlphenvni2-chloro-4-f E-fn-morpholinvllcarboriylktrienvllphenvil sulfide To a stirred solution of the alcohol (368 my, 0.94 mmol) from Example 11 in 5 mL of anhydrous acetonitrile was added activated 4A molecular sieves, TPAP (3.3 mg, 0.0094 mmol), and NMO {(tO mg, J .03 mmol). The mixture was then stirred at room lempcraiurc for 3 hours. The reaction mixture was then quenched with dimethyl sulfide (100 uL). The crude product was filtered through celite, washed with acetonitrile, condensed in vacuo. The titled compound was purified by silica gel column chromatography to give a white solid (216 mg, 59 %).' H NMR (d'-DMSO, Example 58 (2-(4-Fomivlpiperazm-l-vlmethvDphenvllf2-ch]oro-4-( E-(fl-moronolinvlkarbonvD ethenvPphcnyl") sulfide The title compound was prepared by the procedures described in Example 53B substituting morpholine with 1-formyl piperazine. White solid; 'H NMR (d°-DMSO, (&.J= 15.6 Hz, 1H), 7.45-7.52 (m, 3H), 7.98 (d. J = 2.1,1H). MS(DCI/NH,)(M+Hr al mix 486, 488. Exajnple 59 ("2-f £-(n-Morpholinvl>carhonyl)ethenvhphenv1)f2-chloro-4-( E- ca'rbonyl)ethenvl)phenvll sulfide A mixture of bromide (80 mg, 0.18 mmol) from Example 12. acryloylmorpholirte (33 mg, 0.23 mmol), PdCOAcJ^ (2.0 mg. 0.009 mmol), P(o-tolyl), (17 mg, 0.056 mmol), Et,N (39 u.1., 0.27 mmol), and anhydrous DMK (1.0 mL) in a pressure lube was flushed with nitrogen for 5 minutes before it capped and heated at UQ°C over night. TLC indicated almost complete consumption of the starting bromide. The reaction mixture was then allowed to cool down to room temperature, partitioned between EtOAc and water. The aqueous layer was extracted once with EtOAc. The combined organic layer was washed wilh water and brine, dried over Na,SOj, condensed under reduced pressure. The crude product was purified with Gilson Preparative HPLC as described in Example 38B to give the titled compound as a light-brown solid (35 mg, 39%). 'H NMR (dVDMSO. 300 MHz) 5 3.43-3.88 (m, Example 60 2-FormvlphgnvlU2-nitro-4-( £- sulfide The title compound was prepared by the procedures described in Example 57 istituting compound from Example 11 with compound from Example 48. Yellow Example 61 -FormYlphenvlir2-chloro-4-(£-(fl-morpholinvncarbonvlkthenvl)phenvl1 sulfide. N.N-dim ethvl hvdrazone A mixture of the aldehyde (20 mg, 0.052 mmol) from Example ST. 1,1-lethyl hydrazine (3.9 uL, 0.052 mmol) in 0.5 mL of EtOH wilh a tiny amount of 3H was stirred at room temperature over night. The solvent was then removed and product was purified by preparative TLC to give the titled compound (20 mg. Example 62 f2-f(3-n-Mon)holinvhtiropvU-l-^mino)phenvnf2-chloro-4-(£"-('(1-morphoiinvllcarbonvn ethenvllnhcnvll sulfide A mixture of bromide (60 mg, 0.14 mmol) from Example 12, aminopropylmorpholine (24 u.L, 0.17 mmoi), Pd,(dba)3 (1.2 mg. 0.0013mmol), BINAP {2.5 mg, 0.004 mmol), NaO/-Bu (19 mg, 0.20 mmol), 18-crown-6 (50 mg, 0.20 mmol), and anhydrous toluene 0 *"'-) in a pressure tube was flushed with nitrogen for 3 minutes before it was capped and healed at 80 °C over night. The reaction was then stopped, and allowed to cool down to room temperature. The reaction mixture was partitioned between EtOAc and water, and the aqueous layer was extracted once with EtOAc. The combined organic layer was then washed with water and brine, dried over Na,SO„ condensed under reduced pressure. The crude product was purified with Gilson Preparative HPLC as described in Example 38B to give the titled compound as a light-brown oil (30 mg, 44%). 'H NMR (d'-DMSO, 300 MHz)S 1.62 (quintet, J = 6.5 Hz. 2H), 2.15-2.26 (m, 8H), 3.17 (q,y = 6.5 Hz, 2H), 3.22-3.76 (m, 12 H), 3.50 Example 63 (2.4-Dichloropheny[U2-brom6-4-( E-(G-(l-pvnoHdm-2-onlv1piQPVlamino1carhonvn ethenyllphenvl] sulfide Example 63 A (2.4-DichlorophenvD[2-amino-4-f E-((3-f 1 -pyrrol id tn-2-onlv)oropvl ami notcarbonvn ethenvl^phcRvl^ sulfide A mixture of nitro compound (780 mg. 1.58 mmol) from Example 33. SnCl, (1.50 g, 7.91 mmol) in 25 ml. of anhydrous EtOH was refluxeu under nitrogen atmosphere for 90 minutes. The reaction was then allowed to cool down to room temperature, quenched with sat. NaHCO,, extracted with EtOAc (2x50 mL). The combined organic \ayer was washed with water and brine, dried over Na^SOj, condensed in vacuo to give the crude aniline as yellowish brown solid, which was converted to the bromide without purification. ExamTjle_63Ji l,2.4-Dichlorophenvn[2-bromo-4-(' FACS41 -pvrrolidin-2-onlv)Dropvlamino)carbonvn ethenyDphenvl] sulfide To a stiired solution of/-butyl nitrite (57 uL, 0.48 mmol), CuBr, (87 mg, 0.39 mmol)in2.0mLofCH,CNat room temperature was added a solution of aniline from Example 63A (150 mg, 0.323 mmol) in l.OmLof CH3CN. The dark green solution was then heated at 65 °C under nitrogen atmosphere for 90 minutes. The reaction mixture was then allowed to cool down to room temperature, partitioned between EtOAc and 3N HCI. The organic layer was then washed with brine, dried over Na,SO,. condensed in vacuo. The crude product was then purified with Gilson Preparative HP1.C as described in Example 38B to give the titled compound as a light-brown solid (50 mg, 29%). Colorless oil; 'H NMR (d6-DMSO, 300 MHz) 5 1.63 (quintet. J = 7.2 Hz, 2H). 1.91 (quintet. J = 8.4 HA 2H), 2.22 (t, J= 8.4 Hz, 2H), 3.09- Example 64 (2.4-Dichlorophenvnf2-formvl-4-( g-((l-morpholinvl)carbonvi)ethenvhphenvll sulfide Example 64A fl-Fluoro-2-formvl-4-f £-f(]-morpholinvDcarbonvDethenYn benzene The title compound was prepared by the procedures described in Example 59 mbstiluting the bromide from Example 12 with 2-fluoro-5-bromobenzaldehyde. Example 64B f2,4-Dichlorophenv11[2-foniwt-4-( g-((l-morpholinv(1carbonvl>ethenvl1phenYil sulfide The title compound was prepared by the procedures described in Example 32 substituting 4-chloro-3-nicro-cinnamide with the compound from Example 64A. White solid; 'H NMtt Example 65 (2-Chloro-6-formvlphenvl'if2-chloro-4-( E-((4-acetvlpipcrazin-l-vHcarbonvl) ethenyll phenyl] sulfide Example 65 A (2-Carbomethoxvethvl|[2-chloro-4-i' £-((4-acetvlpiperazin-1-vncarbonvH ethenvll nhenvll sulfide The title compound was prepared by the procedures described in Example 1 substituting 2,4-dichlorothiopbenol with methyl 3-mercaptopropionate, and 6-aminc-1-hexanol with 1-acetyl piperazine. Example 65B (2-Chloro-6-formYlphei]vl}\2 ethenvll phenyl] sulfide To a stirred solution of the compound (105 mg, 0.26 mmol) from Example 65A in 2 mL of THF under nitrogen atmosphere at 0 °C was added (-BuOK solution (1.0M,281 u.L, 0.29 mmol). Light orange precipitates appeared immediately. After comptetion of the addition, the reaction mixture was stirred at room temperature for I hour before the solvent was removed on a rotavap under reduced pressure. The yellow thjolate thus obtained was dissolved in 0.5 mLofDMF. and 2,3-dichlorobcnzaldehyde was then added. The mixture was then heated at 80 °C under nitrogen for 2 hours. Reaction was then stopped and the solvent was removed under vacuum. The crude product was purified with Uilson Preparative HPLC as described i Example 66 f2-CvanophenvHf2-chloro-4-(,£'-ff4-acetylpipcrazin-l-vl>carbonvl) ethenvt) phenvfl sulfide The title compound was prepared by the procedures described in Example 65B bstituting 2,3-dichlorobenzaIdehyde with 2-fluorobenzonitrile, giving a white solid. Example 67 ethenyl) phenyl] sulfide Example 67A (2-lsoprop v 1 phen v 1 K'4-bromo-2-c vano phe n v Dsu I fi de The title compound was prepared by the procedures described in Example 1A >s(i luting 2,4-dichlorothiophenol with isopropylthiophenol, and 2-orobenzaldehyde with 2-fluorobenzonitri!e. Example 67B f2-IsopropvIphenvlir2-cyano-4-(£'-(fmorpholin-l-vl)cafbpnyl1 ethenvi) phenyl! sulfide The title compound was prepared by Ihe procedures described in Example 59 substituting the bromide from Example 12 witii the bromide from Example 67A, jiving a white solid. 'H NMR (CDC1„ 300 MHz) 5 1.19 (d, J= 6.9 Hz, 6H), 3.49 Example 68 (2-Bromophenvl1f2-nitro-4-(£'-ff4-acctvlpiperazin-l-vncarbonvn ethenvi') phenyl \ sulfide The title compound was prepared by the procedures described in Example 32B instituting 2.4-dichlorothiophenol with 2-bromothiophenol, providing a light-yellow Example 69, (2-fPvrrolidin-1-yl>phenvnr2-chloro-4-( E-Hmorpholin-l-vlkarbonvn ethenvD phenyl 1 sulfide To a stirred solution of bromide (75 mg, 0.17 mmol) from Example 12 in toluene in a sealed tube was added sequentially pyrrolidine (18.4 mL, 0.22 mmol), Pd,(dba)3 (3.0 mg, 0.0034mmol), BINAP (6.0 mg, O.OlOmmol), followed by NaOBu (26 mg, 0.27 mmol). The resulting mixture was then flushed with anhydrous N; for 2 min before it was capped and'heated at 90 °C for 24 h. The reaction mixture was then allowed to cool down to room temperature and partitioned between ethyl acetate and brine. The organic layer was then dried with Na.SO,, filtered, and concentrated in vacuo. The crude product was purified using Gilson Preparative HPLC as described in Example 38B to give the title compound (40 mg. 55% yield) as a white solid: 'H NMR (CDC1„ 300 MHz) 8 1.83 (br s, 4H). 3.40 (br s, 4H), 3.56-3.80 (m, 8H). 6.57 Example 70 .(2-Methoxyphenvh-[2-chloro-4(E-[(morpholin-l-vl'lcarbonvl1ethenvnphenvllsu)fide The title compound was prepared according to the procedures of Example I. giving a white solid, m.p. 162-164C. 'H NMR (CDC1.„ 300 MHz) 5 3.60-3.78 (m. Example 71 (2-lsoprooYli}kenvi)l2-rittTO-4- ethenvl) phenyl] sulfide Example 7) A 1 - /e/7-Butvoxvcarbonyl ■2-carbomethoxvpiperazine 2-Carbometboxypiperazine was treated with benzyl chloroformate (1.0 eq) in aqueous NaHCO, to give 1- ben zyloxy car bony 1-3 -carbomethoxypiperazine. This material was treated with di-rerf-butyldicarbonate (1.1 eq) and triethylamine (1.0 eq) in THK to produce l-/er(-butyoxycarbonyl-4-benzyloxycarbonyl-2- carbomethoxypiperazine. Hydrogcnation of this compound in methanol using 10% Pd-C gives the title compound after filtration and solvent removal. Example 71B (2-Isopropvlphenvn[2-nitro-4-(£-f(3-carbomethoxvpipera7in-l-vl1carbonvl) ethenvi) phenyl] sulfide A mixture of (2-isopropylphenyl)[2-nilro-4-£-(carboxyethenyl)phenyl] sulfide (prepared according to the procedures of Example 32), the amine from Example 71A (1.0 eqX2-(]H-ben20triazo]-]-y])-l,l,3,3-Ieiramethy!uronium tetrafluoToboraie (1.0 eq), and diisopropylethylamine (2.0 eq) in DMF was stirred at ambient temperature for 4 hr. Ethyl acetate was added, and the mixture was washed sequentially with IN HC1, bicarb, and brine. The resultant yellow solid was treated with 1:1 TFA/dichloromediane at ambient temperature to give the title compound as a yellow solid. 'H NMR (DMSO-d,, 300MHz) 8 1.15 Example 72 (2-Methv1phenvD[2-nitro^l-f £-fO-carboxarnido-4-carbobenzoxvpiperaziri-l- yl)carbonvl)eihenyh phenvll sulfide Prepared according to the procedures of Example 71, giviny a yellow solid. 'H NMR (DMSO-d,,, 300MHz) B 2.30 (s, 3H); 2.80-4.80 (br m. 7H); 5.05-5.15 (br m, 2H); 6.61-6.67 (br m, 1H); 7.02-7.64 (m. 13H); 7.80-7.90 (brm, 1H); 8.56-8.65 (br m, 1H). MS (APCI) (M+H)- at m/z 561. Anal calcd for CJIMNtS1O(1-0.42CHiCOOCH1CH1: C, 61.66; H, 5.29; N, 9.38. Found: C, 61.41; H, 5.28; N, 9.53. Example 73 f 2-1 tjopropylphen y ft [2- nitro-4-( £-((2 -ca rbom ethox v-4-ftrf- bu i ox vcarbon y I pi perazi n- 1 -vltoarbonvlkthenvD phenyl! sulfide Prepared according to the procedures of Example 71, giving a yellow solid. 'H NMR (DMSO-d,, 300MHz) 5 1.13 {d, J - 6.6 Hz, 6H); 1.40, 1.41 (s, s, 9H); 2.72-3.08 (br m, 1H); 3.17-3.24 (ra, 1H); 3.30-3.40 (m, 1H); 3.68 (br s, 3H); 3.79-4.51 (br m, 4H); 5.06, 5.36 (br s, br s, 1H); 6.61-6.67 (m, 1H); 7.30-7.62 (m, 6H); 7.85-7.93 [br m, 1H); 8.64-8.69 (br m, 1H). MS (APCI) (M+H)" at m/z 570, Anal calcd for "MH^SAO-^QH,,: C, 61:66; H? 6.43; N, 7.21. Found: C, 61.69; II. 6.35; N, 7.Q2. Example 74 (2-lsopropvlphenvn[2'nilro-4-(£-ff2-carboxv-4-/erf-hutoxvcarbonvlpiperazin-1- ypcarbonvllethenvh phenyl] sulfide Prepared according to the procedures of Example 71, giving a yellow solid. lH ■1MR (CDC1„ 300MHz) 5 1.14 (d, J = 6.6 Hz, 6H); 1.45 (s, 9H); 2.72^.75 (br m, >H); 3.38-3.49 (m. 1H); 5.78 (br s. 1H); 6.68, 6.72 (s, s, 1H); 6.88, 6.94 (br s, br. s. H); 7.26-7.71 (m, 6H); 8.44 (br s, III). MS (APCI) (M-H)* at m/z 554. Anal calcd or CaH^N^Cy C, 60.53; H, 5.99; N, 7.56. Found: C, 60.42; H, 6.21; N, 7.31. Example 75 f2-Isopropy]phenvlir2-mfluoromethvl-4- eihenvl) phenyl] sulfide The title compound was prepared according to the procedures of Example 1. "NMR(CDC13, 300 MHz)5 7.78 (s. 111), 7.62 (d, lH, J = 15.5 Hz), 7.43-7.49 (m. 3H), 7.37(d, lH.J = 8.1Hz),7.23(m, 1H),6.85 (d, IH, J= 15.5 Hz),6.82 (d, 1H, J = 8.5 Hz), 3.63-3.77 (in. 6H), 3.45-3.55 (m, 3H), 2.14 (s, 3H), 1.17 (d, 6H, J - 6.6 Hz). MS (ESI) m/z 477,499,975,953. Anal. Calcd for C25H27F3N2O2S ■ 0.5 EtOAc: C, 62.29; H, 6.00; N, 5.38. Found: C, 62.40; H, 6.21; N, 5.35. Example 76 (2-IsopropvlphenvDf2-triiluorometbv]-4-( £-((morpholiri -1-vhcarhonvl) ethenvll phenyl] sulfide The title compound was prepared according to the procedures of Example 1 ■ 'H NMR (CDC1.„ 300 MHz) 7.78 (s, 1H). 7.62 (br, 1H), 7.33-7.48 (m, 3H). 7.22 (m, 1H), 6.85 (m, 1H). 6.80 (d, 1H, J - 8.5 Hz). 3.73 (br. 8H), 3.49 (dq, IH, J, = J, = 6.9 Hz), 1,17 (d. 6H, J = 7.1 Hz). MS (ESI) m/:A3h, 871.893. Anal. Calcd for C23H24F3N]02S: C. 63.43; H, 5.55; N, 3.22. Found: C.63.12; H, 5.8i: N. 3.10. Example 77 f2-Isopropvlphenvn[j-trifluoromethvl-4-(E-((3-(pvrrolidin-2-on-l-vnnrop-1- vlamino)carbqnynethertyl)phenvlfautfide The title compound was prepared according to the procedures of Example 1. 'H NMR (CDClj. 300 MHz) S 7.77 (s, 1H). 7.52(d, 1H, J = 15.4 Hz), 7.43-7.51 (m. 3H), 7.36 (d, 1H, J = 8.8 Hz), 7.22 (m, IH). 7.10 (br, 1H). 6.80(4 1H, J- 8.4 Hz), 6.44 (d, IH, J = 15.4 Hz), 3.49 (dq, IH, J, - J, - 6.9 Hz), 3.40 Exarnple 78 (2-Isopropy]phenvl)l2-trifluoromethvl-4-f ^-ffcyclobutviaminoteaTbonvn ethenvl) phenyl! sulfide The title compound was prepared according to the procedures of Example 1. H NMR (CDC1,, 300 MHz) 5 7.76 (s, ]H), 7.52 (d, ]H, J = 15.4 Hz), 7.43-7.49 (m. Example 79 f2-Isopropvlphenvn[2-trifluoromeihvl-4-l'£-(fcvc]opentviaminokarbonvn ethenvh phenyl! sulfide The title compound was prepared according to the procedures of Example 1. Example 80 f2-lsopropvlphenvl1f2-lrifliioromethvl-4-i'£-(f5-hvdTOXvpent-l-ylaminolcarbonvl') ethenvh phenyl] sulfide The title compound was prepared according to ihe procedures of Example 1. Example 81 (2-Isopropvlphenvni2-nitro-4-{ g-((3-carbomelhoxv-4-acetvlpiperazin-l- vllcarbonvllethenvH phenyl] sulfide Prepared according lo the procedures of Example 71, giving a yellow solid. (APCI) (M+H)' at ro/z 512. Anal calcd for CJlJrt&O,,: C, 61.04; H, 5.71; N, 8.21. Found: C, 61.40; H, 6.05; N, 7.88. Example 82 f2-Biphenvl)f2-chloro-4-f g-KmorohQlin-l-vhcarbonvli L eihenvll phenyl) sulfide To a stirred solution ofbromide from Example 12(60mg,0.14mmol)inl mL of toluene was added 0.5 mL of sat. Na,CO„ Pd(PPh3)4 (8 mg, 0.007 mmol), phcnylboronic acid (17 mg, 0.14 mmol). The mixture was flushed with nitrogen and heated at 100 °C for 3 h. The reaction mixture was then allowed to cool down to room temperature and partitioned between ethyl acetate and brine. The organic layer was then dried with Na3S04, filtered, and concentrated in vacuo. The crude product was purified using Gilson Preparative HPLC as described in Example 38B to ■give the title compound as colorless oil (40 mg. 67% yield); 'H NMR (CDC13, 300 MHz) & 3.58-3.86 (m, 8H), 6.77 {d,J= 15.6 Hz, 1H), 6.86 (d, J= 8.4 Hz, 1H), 7.67 (dd.J= 2.1, 8.4 Hz, IH), 7.29-7.40 (m, 3H), 7.40-7.48 (m, 6H), 7.56 (d,J= 15.6 Hz, !H>, 7.65 (d, J* 1.8 Hz, IH). MS (APCI") (M+H)" at m/z 436, 438. Example 83 (3.4-DimethvlpbenvHr2-nitro-4-(E-((4-acetvlpiDerazin-1 - vljcarbonvlkthenvlmhenyllsulfidc To a solution of the compound of Example 32A (40 mg, 0.12 mmote) in 2.5 mL of dimethyl formamide was added 3,4-diraethyllhiophenol (17 mg, 0.12 mmole), followed by potassium carbonate powder (20 mg, 0.14 mmole). The mixture was heated at 100°C for 20 h. The solvent was removed using Nj gas flow. Water (5 mL) was then added to the residue, the resulting precipitate was collected through filtration, washed with cold water, and air dried to give me title compound (42 mg, 81%) as light yellow solid. 'H-NMR (CDC1,, 400 MHz) 5 2.08 (s, 3H). 2.23 (s, 3H), 2.27 (s, 3H). 3.45 (br. m, 2H), 3.63 (br, m, 611), 6.79 (s, IH), 6.82 {d, J = 19 Ik, IH), 7.18 (d, J = 19 Hz. IH), 7.24 (dd, J = 4,19 IIz. IH), 7.27 (s, IH), 7.34 (d, J = 21 Hz, IH). 7.56 (d, J = 39 Hz, 1H), 8.32 (d, J = 4 Hz, 111). MS (APCI) (M+H)T at m/z440. FAB High Resolution MS calculated m/z for C^NAS (M^H)*: 440.1644. Observed m/z: 440.1646. Example 84 f2-Bromophcnvn[2-[rifluoromethvl-4-(E-f(4-acetvlpiperazin-l-vl)carbonvi) cthenvl) phenyl] sulfide The title compound was prepared by the procedures described in Example 9 substituting 2,4-dichlorothiophenol with 2-bromothiophenol, and 3,4-dichlorobenzaldehyde with 4-fluoro-3-trifluoromethylbenzaldehyde, to give a white solid. 'H NMR (d'-DMSO, 300 MHz) 6 2.04 (s, 3H), 3.43-3.80 (m, 8H), 7.21 (dd, J = 2.1,8.4 Hz, IH), 7.24 (d, J= 8.4 Hz, IH), 7.33 (td, J= 2.1,7.65 Hz, IH), 7.42 (td, J = 1.8,7.65 Hz, IH), 7.45 (d, .7=15.6Hz, IH). 7.58 (d,J= 15.6 Hz. IH), 7.78(dd,J= 1.8,8.4 Hz, 1H), 7.96 (dd, J= 1.8,8.4 HZ, 1H), s.,o {a,j= l.s Hz, 1H). MS (AFfJO (M+NH4) at m/z 530,532,534. Example 85 (5-Indolvl)|2-chloro-4-f £-ff 4-acetvlpiperazin-1-vlkarbonvH ' ethenvl) phenyl] sulfide To a stirred solution of 5-iodo indole (255 mg, 1.05 mmol) in 5.0 mL of anhydrous UMK was added the potassium thiolate (457 mg, 1.26 mmol) from Example 65B, followed by K,CO, (t 74 mg. 1.26 mmol), and cuprous iodide (20 mg, 0.11 mmol). The resulting mixture was then heated at 120 °C for overnight. The reaction mixture was then allowed to cool to ambient temperature and poured into water. The aqueous mixture was extracted twice with 25 mL of ethyl acetate. The combined organic layer was then washed with water and brine, dried over Na,SO„ filtered, concentrated on a rotavap under reduced pressure. The crude product was purified using Gilson Preparative HPLC as described in Example 38B to give the title compound (115 mg, 25 % based on the iodide) as a light-brown solid. 'HNMR(d°-DMSO, 300 MHz) S 2.03 (s, 3H), 3.40-3.78 (m, 8H). 6.51 (d. ./= 8.4 Hz, 1H), 6.53 (S, 1H), 7.23 (dd,./* 2.1, 8.4 Hz, 1H), 7.27 (d,.7=15.6Hz, 1H), 7.39 (d,J= 15.6 Hz, 1H), 7.41 (dd,./- 1.8. 8.4 Hz, 1H). 7.49 (t, J = 2.7 Hz. 1H), 7.56 (d,./ = 8.4Hz. 1H). 7.85 (d, J = 1.8 Hz, 1H), 7.99 (d, J = 1.8 Hz, 1H). MS (APCI) (M+NHj)" at m/z 440, 442. Anal. Calcd for C23H22CIN3O2S ■ 0.53 CH2C12: C, 58.28; H, 4.79; N, 8.66. Found: C, 58.31; H, 4.93; N, 8.65. Example 86 f5-BenzodioxolvDr2-chioro-4-f E-f(4-acetvlpipera2in-l -vHcarbony]) ethenvll phenvll sulfide The title compound was prepared by the procedures described in Example 85 substituting 5-iodoindole with' 1 -iodo-3,4-methy]enedioxybenzene, providing a white Example 87 f2-lsopropvlphenv1)[2-nitro^l-f E-((2-carr»methoxvpiperazin-l-vlkarbonvlkthcnvl) phenyl] sulfide Prepared according to the procedures of Example 7i, giving a yellow solid. 'H Example 88 (2.3-DimeihQxvphenvlV[2-chloro-4l"E-[fmorphoIin-l-v]'lcarbonvlleihenvl'>phenYll sulfide The title compound was prepared according to the procedures of Example I, giving a white solid, m.p. 148-150C. lH NMR (CDCl,„ 300 MHz) 5 3.60-3.78 (m, 8H), 3.85 (s. 3H), 3.91 (s, 3H), 6.78 fd, J=16Hz, 1H), 6.86-6.98 (m, 3H), 7.20 (dd, J=9Hz, 2Hz. !H), 7.54 (d, J=2Hz, 1H), 7.58 (d, J=16Hz, IH). Anal. Calcd. for C,,H,,C1N04S: C, 60.06; H, 5.28; N, 3.33. Found: C. 59.72; H7 5.34; N, 2.97. Example 89 (2-FluoropherwlU2-nitro-4-(E-(f4-acctvlpiperazin-l-vhcarbonvttethenvnphenvHsuifide The iille compound was prepared by the procedures described in Example 83 substituting 3,4-dimethylthiophenol with 2-fluorothiophenni. Yellow solid (40 mg, 78%); 'H-NMR (CDC1,, 400 MHz) 8 2.17 (s, 3H), 3.56 (br. m. 2H), 3.77 (br. m, 6H), 6.88 (dd, J =3,21 Hz, IH), 6.93 (d, J - 39 Hz, IH), 7.26 (dd. J = 3,2! Hz. IH), 7.33 (dd, J = 3,19 Hz, IH), 7.49 (br, d, J = 20 Hz, IH), 7.58 (m, IH), 7.66 (m, 2H), 8.46 (d,J = 4Hz, IH). MS(APCI)(M+H)'atm/z430. FAB High Resolution MS calculated m/z for Cj^NAFS (M+II)': 430.1237. Observed m/z: 430.1246. Example 90 f2-Bromophenvl)r2-irifiuoromethvM-f g-((4-(fer)-butoxvcarbonvl)pir)erazin-l- vDcarbonvnethenvn phenyl] sulfide The tille compound was prepared by the procedures described in Example I substituting 2,4-dichlorotiiiophenoi with 2-bromothiopbenol, 2-chlorobenzaIdehyde with 4-i]uoro-3-trifluoromethy]benzadehyde, and 6-amino-l -hexanol with /-butyl 1 -piperazinecarboxylatc, to give a white solid. lH NMR (CDCl,, 300 MHz) d 1.48 (s, Example 91 f2-(PvtTolidin-l.yl)phenvl'l[2-trifluoromethvl-4-( E-(f4-C/crf-butoxvcarbonvnDipfm-/in-!-vhcarborivheiherivh phenvH sulfide The title compound was prepared by the procedures described in Example 69 substituting the bromide from Example 12 with the bromide from Example 90, to give a white solid. 'H NMR (CDCl,, 300 MHz) S 1.85 (i, 9H), 1.85 (br s, 4H), 3.32-3.55 (m, 8H), 3.55-3.78 (m, 4H), 6.76 (d. J= 8.4 Hz, 1H), 6.82 (d,J = 15.6 Hz, 1H), 7.23-7.45 (m, 5H), 7.61 (d, J= 15.6 Hz, 1H), 7.75 (brs, 1H). MS (APC1') (M+H)" at m/z 562. Example 92 (l7-t;arhnx3midophenvnf2-nitro-4-Cg-if(l'J-acetvlDiperazin-l-vncarbonvll ethenvl) phenyl] sulfide Example 92A 0-Carhoxyphenyl1f2-nitrc-4-( E-((4 -acetyl pi perazin-1 -yltcarbonvn ethenvl) phenyl) sulfide The title compound was prepared by the procedures described in Example 32B substituting 2,4-dichlorothiophenol with 3-mercaptobenzoic acid. Example 92B O-Carboxamidophenvlip-nitrQ-^fE-tM-acetvlninerazin-l-vllcarbonvl) ethenvh phenyl) sulfide To a stirred solution of benzoic acid from Example 92A (40 mg, 0.088 mmo!) in 1 mL of anhydrous DMF with HOBT (15 mg, 0.097 mmol) was added EDAC (19 mg. 0.097 mmol), followed by ammonium chloride (large excess). The pH of the solution was adjusted to 6 with addition of triethyl amine. The resulting mixture was then stirred at ambient temperature for 6 h. Water was added to quenched the reaction. The product precipitated out after stirring for 30 min, which was then isolated by filtration and dried in vacuum oven to give a light yellow solid (25 mg, 63% yield). 'H Example 93 n-fHvdrfixvmethvltphenvflfl-niiro-^ffi-ff^acetvlpiperazin-l-vHcarbonvl) ethenvl) phenyl] sulfide To a stirred solution of benzoic acid from Example 92A {255 mg, 0.56 mmol) in 5 mL of anhydrous THF at 0 °C was added in mm Et,N (102 mL, 0.73 mmol) and ethyl chloroformate (70 mL, 0.73 mmol). After 60 min, the reaction mixture was filtered through celile plug into a stirred solution of NaBH4 in water al 0 *C. The Example 94 Phenyl [2 ■trifluoromethvl-4-f £-(Y4-(rerf-butoxvcarbonvnpiperazin-1 -vltcarbony^ethcnvH phenvll sulfide The title compound was obtained as a reductive side product from the reaction mixture described in Example 91, as a colorless oil. 'H NMR (CDC1,, 300 MHz) 8 High Resolution MS calculated m/zfor C2IH,2NjO,S (M+H)*: 428.1280. Observed m/z: 428.1296. Example 125 (3.5-Dichlorophenvl)f2-nitro-4-( £-((4-acetvlpiperazin-l-vncarbonvllethenvnphenvnsulfide The title compound was prepared by the procedures described in Example 83 substituting 3,4-dimethylthiophenol with 3,5-dichlorothiophenol. Yellow solid (12 Example 126 (2-Bromophenvl'lf2-chloro-4-('E-f(3-C55'-acetoxvmethvl-pviTolidin-2-on-l-vnprop-l- vlaminolcarbonvP ethenvltphenvllsulfide To a solution of the compound of Example 113 (0.0466g, 0.0889 mmol) in CH2C12 (.5 mL) was added triethylamine (0.024 mL, 0.18 mmol) and acetic anhydride (0.0088 mL, 0.0933 mmol). After 12 h the reaction was diluted with MeOH (1.5 mL) and purified by preparative HPLC to provide the title compound (.0458 g. 91%). 'H- NMRfDMSO-d*, 300MHz) 5 8.14 (t,./= 5.7 Hz, 1H), 7.80 (m, 2H), 7.53 (dd, J= 8.5, Example 127 (2-Bromophenvl')f2-chloro-4-( E-(( 3-C55-methoxvmethvl-pyrrolidin-2-on-1 -yHprop-1 -ylamino)carbonvl)ethenyl)phenvl]sulfide Sodium hydride (0.0088g, 0.22 mmol, 60% dispersion) was added to a solution of the compound of Example 113 (0.0524g, 0.1 mmol) in DMF (0.5 mL). After 15 min, iodomethane (0.025 mL, 0.4 mmol) was added and the reaction was stirred for 12 h. The reaction was diluted with EtOAc (7 mL) and extracted with sat. NH4C1 (1x2.5 mL), extracted with H20 (2x2.5 mL), rinsed with brine (2.5mL), dried over Na:S04, filtered, and concentrated in vacuo. The crude products were diluted with MeOH (1.5 mL) and purified by preparative HPLC to provide the title compound Example 128 (2-Bromophenvl1[2-chIoro-4-(E-(f 3-(4/?-hvdroxvmethvl-pvrTolidin-2-on-1 -vDprop-1 -vlaminolcarbonvll ethenvnnhenvljsulfide The title compound was prepared by the procedures described for Example 113 substituting l-(3-aminopropyl)-5-{(S)-thexyldimethylsilyloxymethyl)-2-pyrrolidinone with l-(3-aminopropyl)-4-((/f)-thexyldimethylsilyloxy)-2-pyrrolidinone. 'H-NMR (DMSO-d6,300MHz) 8 8.13 (t,./ = 5.5 Hz, 1H), 7.80 (m, Example 129 Phenvl[2-nitro-4-( £-(f4-acetYlpiperazin-l-vltearbonvDethenvnphenvl1sulfide The title compound was prepared by the procedures described in Example 83 substituting 3,4-dimethylthiophenol with thiophenol. Yellow solid (36 mg, 73%); 'H-NMR (CDC1„ 400 MHz) 8 2.20 (s, 3H), 3.59 (br. m, 2H), 3.78 (br, m, 6H), 6.92 (d, J Example 130 (2-Dimethvlaminophenv0r2-nitro-4-( £-((4-acetvlpipera7.in-1 -vl')carbonvl') ethenvH phenvll sulfide To a stirred solution of aniline from Example 47 (21 mg, 0.049 mmol) in 1 mL of ethanol was added Me2SO Example 132 O-CG-n-ImidazolvnpropvnaminocarbonvnDhenvnp-nitro-^-f £-((4-acetvlpipera2in-l-vDcarbonvDethcnvll phenyl! sulfide The title compound was prepared by the procedures described in Example 92B, substituting ammonium chloride with 3-aminopropyl-l -imidazole, as a light yellow solid. 'H NMR (de-DMSO, 300 MHz) d 1.96 (quintet, J = 6.98 Hz, 2H), 2.04 Example 133 (3-((2-( 1 -Morpholinvnethvnaminocarbonvl )phenvlM2-nitro-4-( £-((4-acetvlpiperazin-1-vDcarbonvPethenvP phenvll sulfide The title compound was prepared by the procedures described in Example 92B, substituting ammonium chloride with 2-aminoethyl-l-morpholine, as a light yellow solid. 'H NMR (d*-DMSO, 300 MHz) 8 2.04 (s, 3H), 2.44 (br s, 4H). 3.20-3.80 (m, 16H), 6.87 (d,J= 8.4 Hz, IH), 7.41 (d,J= 15.6 Hz, 1H), 7.54 (d, J= 15.6 Hz, Example 135 (2■^sop^opvlphe^^'^)f2-Tlitro-4-l, £4f4-fonnvlpiperazin-1-vlfcarbonvnethenvD phenyl] sulfide Prepared according to the procedures of Example 71, giving a yellow solid. ■H NMR (DMSO-d., 300MHz) 8 1.14 (d, J = 7.1 Hz, 6H); 3.30-3.38 (m, 1H); 3.38- 3.77 (br m, 8H); 6.64 (d, J = 8.5 Hz. Ill); 7.34-7.62 (m, 6H); 7.88-7.92 (dd, J = 8,5, 1.7 Hz, tH); 8.08 (s, 1H): 8.65 (d, J = 1.7 H7, 1H). MS (APCI) (M+H)" at m/z 44o. Example 137 (2-Ethoxvphenvl)-i2-ch)oTO-4(E-^0'Sthoxvcarbonvlp}pendin-]-vl)carbonYllelhenvl) phenvllsulfide The title compound was prepared according to the procedures of Example 97. 'H NMR (CDC1,, 300 MHz) 8 1.25 (t, J= 7 Hz, 6H), broad peaks totaling 9 protons at 1.50-1.62,1.65-1.92,2.01-2.15,2.45-2.55.2.95-3.05,3.13-3.30,3.55-3.68, 3.9O-4.10, 4.05 (q, J=7Hz,2H). 4.15 (q. J=7Hz, 2H). 6.84 (d. J=9Hz, 1H), 6.80-6.95 {broad, 1H), 6.94-6.99 (m, 2H), 7.18 (dd, J=9Hz, 2Hz, HI), 7.34-7.41 (m, 2H), 7.52 (d, J-!5Hz, 1H), 7.55 (d, J=2Hz, 1H). Anal. Calcd. for Example 139 Example 140 f2,4-DimethvlphenvD[2- nitro-4-( E-f(4-acetylpipcrazin-l-vDcaibon v Hethcnv 1 )phen v 11 su Ifi de The title compound was prepared by the procedures described in Example 83 substituting 3,4-dimethylthiophenol with 2,4-dimethylthiophcnol. Yellow solid (40 mg, 76%); 'H-NMR (CDC13,400 MHz) 5 1.54 (br, s, 2H), 2.14 (s. 3H), 3.53 (br, m: (M+H)* at m/z 440. FAB High Resolution MS calculated m/z for C,.,H,6Nj04S (M+H)*: 440.1644. Observed m/z: 440.1656. Example 14% Vlicarbnnvl1ethenvl1phenvl]sulfide The title compound was prepared by the procedures described in Example 83 instituting 3,4-dimethylihiophenoi with 4-methoxythiophenol. Yellow solid (44 mg, 13%); 'H-NMR (CDC1,, 400 MHz) 5 2.09 (s, 3H), 3.48 (br, m, 2H), 3.66 (br, m, 6H), Example 143 High Resolution MS calculated m/zfor C,,H,,N,0,C1S (M+H)': 446.0941. Observed m/z: 446.0953. Examnle 144 C2-Chloro. 4.5-diamittophenvn[Z-chloro-4-( E-((4-acetvlpiperazin-l- yllcarbonYDethenvh phenyl] sulfide Example 144A (2-Chloro. 4-nJlro.5-arninophcnv1l[2-chloro-4-( £-f(4-acetvlpiperazin-l- vl tea rbonv Heme nvl) nhenvll sulfide The title compound was prepared by the procedures described in Example 65B substituting 2,3-dichloroben*aldehyde with 4,5-dichloro-2-nitroaniIine. Example 144B (l-Chloro. 4.5-diaminophenvDF2-chloro-4-( £-f(4-acetvlpiperazin-l- vncarbonvl'lcthenvh phenyl] sulfide To a stirred solution of nitrobenzene from Example 144A (170 mg, 0.34 mmo!) in 2 mL of EtOH was added SnCl, (325 mg, 1.72 mmol). The mixture was then refluxed under nitrogen atmosphere for 2 h. The reaction was allowed to cool down to ambient temperature, quenched with sat. NaIIC03, extracted with ElOAc(2x20 mL). The combined organic layer was washed with brine, dried over Na;SO(, concentrated in vacuo. The residue was then purified on Gilson preparative HPLC as described in Example 38B to give the title compound (70 mg, 44% yield) as a light yellow solid. 'H NMR (d*-DMSO, 300 MHz) 8 2.04 (a, lit). 3.42-3.80 (m. Example 145 (3.4-Diaminopl]envn[2-chloro-4-(£-((4-aceTvlpipeTazin-l-vhcarhonvhelhenvn phenyl) sulfide The title compound was prepared by the procedures described in Example 144, substituting 4,5-dichiorcnitroaniI(ne with 5-chloronirroaniIrne, resulting in a light Example 146 f6-Chlorobenzimidazol-2-on-5-vl)f2-chloro-4-( g-((4-acetylpiperazin-1 - vDcarbonvDethenvll phenyl] sulfide A mixture ofdianilisc from Example 144(35mg. 0.075 mnwJ) and CDJ (J 3 mg, 0.075 mmol) in THF was stirred at ambient temperature for one day. Solvent was then removed under reduced pressure. The crude product then purified on a Gilson preparative HPLC as described in Example 38B to give the title compound (12 mg, 32% yield) as a white solid. 'H NMR (d6-DMSO, 300 MHz) 6 2.04 (s, 3H), 3.40-3.80 Example 147 n-Methvlindol-7-vn[2-chJQro-4-(£-f(4-acctvlpiperazin-l-vl>carbonvl)ethenvi) phenyl] sulfide The title compound was prepared by the procedures described in 85. ibstituting 5-iodoindole with A'-methyl-7-bromoindole, giving a light brown solid. Example 148 f2-Hvdroxv. 4-aminophenyJ)f2-chiorQ-4- Exait}p|e 150 (2-Isoproovlphenvl)[2-nitrQ-4-(£~f(4-(pvridine-2-carbonv])niperazin-1- yllcarbonvllethenvn phenyl] sulfide Prepared according to ihe procedures of Example 71, giving a yellow solid. 'H NMR (DMSOd,, 300MHz) 5 1.14 (d, J = 6.8 Hz, 6H): 3.30-3.40 (m. III); 3.51-3.83 (br m, 8H); 6.61-6.66 (br m, 1H); 7.30-7.65 (m, 8H); 7.83-7.97 (m, 2H); 8.57- Example 152 C2-Isopropvlp)icnvl)f2-nilro-4-f ^■i,f2-carbomelho-xv-4-nierhi>xvc3rbpriv)piperazJj]-l-vl)carbonvnethenv)i phenyl] sulfide Prepared according to the procedures of Example 71, giving a yellow solid. 'H NMRfPMSO-d,. 300MHz) 5 1.14 (d, J = 7.1 Hz. 6H); 2.70-3.95 (br m, 4H); 3.30-.40 (m, 1H); 3.61, 3.61 (s, s, 3H); 3.65, 3.67 (s, s. 311); 4.16-4.50 (brm, 2H); 5.08-.39 (br m, 1H); 6.64 (dd, J = 8.5, 5.1 Hz, 1H); 7.30-7.63 (m, 6H); 7.83-7.94 (m, 1H); ) .62-8.67 (m, 1H). MS (APCI) (M+H)" at m/z 528. Anal calcd for C^Hj.N.SAO.lSC.H,,: c, 59.94; H, 5.87; N, 7.72. Found: C, 59.87; H, 5.94; N, 7.59. Example 154 (2-Isopropvlphenvn[2-niiro-4-f E-iG'Carbomethoxv-4-meihvlpiperagin-1 - yltearbonvliethenvh phenyl] sulfide Prepared according to the procedures of Example 71, giving a yellow solid. 'H NMR (DMSO-d,, 300MHz) 8 1.14 (d, J = 7.0 Hz, 6H); 2.25, 2.26 (s, s. 3H); 2.20- 3.98 ( hr ra, 8H); 3.57, 3.63 (s, s, 3H); 6.63 (d, J = 8.5 Hz, 1H); 7.30-7.63 (m. 6H); 7.91 (dd, J = 8.5,1.5 Hz, 1H); 8.60-8.68 (br ra, 1H). MS (APCI) (M-H)* at m/z 484. Exumpie 155 (2-EtiioxvphenvlV[2-ctiloro-4(£-i(3-carboxvpipcridiri-l-vncia-bonvllethcnvi)phenvll sulfide The compound ofExample 137 was hydrolyzed using an excess of aqueous 10%NaOH in methanol, stirring overnight. The reaction mixture was concentrated in vacuo, water was added, and the solution was extracted with ether. The mixture was acidified; the resultant solid was collected by filtration and dried overnight in a resultant acid (303 nig, 0.631 mmol) was dissolved in 3 ml MeOH. A KOH solution (38 mg, 0.59S mmol, of 87.6% KOH) in 1 ml MeOH was added. The resulting solution was concentrated in vacuo, and 5 ml. ether was added. The mixture was stirred for one hour to form a powder, which was filtered and dried in the vacuum oven at 60C to yield 307 mg of a solid, water soluble product. Example 155 f2-EthoxvTJhenvlWf2-chloro-4fE-["^-carboxvp]'peridin-l-vlk:arrionvlTpthenvl|phpnvlI sulfide The compound of Example 137 was hydrolyzed using an excess of aqueous 10% NaOH in methanol, stirring overnight. The reaction mixture was concentrated in vacua, water was added, and ihe solution was extracted with ether, giving a white Exampic 156 2 - Et hox yphen v IV [2 -C hi oro-4 (E- [Y2-eth ox vc arbon vl pi peri din-1 ■ v H carbon vHethe nyl) phenvll sulfide The title compound was prepared according to the procedures of Example 97. i NMR (CDClj, 300 MHz) 8 1.24 (t, J=7Hz, 311), 1.28 (t, J=7IIz, 3H), broad peaks Haling 9 protons at 1.35-1.55, 1.65-1.80,2.25-2.38,3.33-3.45. 3.95-4.05,4.15-4.28. .60-4.80,5.44-5.50, 4.05 (q, J=7Hz, 2H), 4.20 (q, J=7Hz, 2H). 6.80-6.98 (m, 4H), . 12-7.20 (m, I H)7.35-7.43 (m, 2H), 7.50-7.58 (m, 2H). Anal. Calcd. for 1SH2,C1N04S: C, 63.35; H, 5.95; N, 2.95. Found: C,63-51; H. 6.22; N. 2.61. Kxample 158 (2-Ethox-vphenvh-f2-chloro-4f£-[f2-carboxvpiperi sulfide The compound of Example ]56washydralyzed. and the salt formed, according to the procedures of Example 155. m.p. 170-171C. 'H-NMR (DMSO 300 MHz) 5 1.16 (t, J=7Hz, 3H). broad peaks totaling 9 protons at 1.20-1,49,1.51-1.75, 2.10-2.27,2.55-2.65, 3.10-3.21,4.20-4.29,4.35-4.45, 5.13-5.25, 4.05 (q, J=7Hz, 211), 6.80 (d, J=9Hz, 1H), 6.97-7.07 (m, 1H), 7.15 (d. J=9Hz. 1H), 7.29-7.57 (m, 5H), 8.02 (S,1H). Anal. Calcd. for CMHMC1N04S: C,61.94;H,S.42;N, 3.14. Found; C, 61.91;H, 5.48; N, 2.90. Example 60 f2-Elhoxvphenv)1[2-trifluoromelhvl-4-i'£-»3- Example 61 f2-Ethoxvphenvnf2-trif]uofomethvl-4-f£-(f4-acetvlpiperazin-l-yl)carbonvl)eihenvl) phenyl] su.fide Example 163 (2-Ethoxvphenvl)(2-irifluoromethvl-4-fg-((4-(2-furvlcarbonvllDiperazin-l-yikarbonvl)elh.envl') phenyl] sulfide The title compound was prepared according to the procedures of Example 71. 'H NMR (CDCI.,, 300 MHz) 5 7.80 (d, 1H, J - 1.5 Hz), 7.66 (d. 1H, J = 15.4 Hz), Example 165 f2-EthoxvnhenvlV[2-chloro-4f£-|(4-carboxvpipcridin-l-vlkarbonvl1ethenvl'iphenvl] sulfide The compound of Example 164 was hydrolyzed, and ihe salt formed, according to the procedures of Example 155. m.p. 165-166C. 'H-NMR(DMSO 30Q MHz) b 1.25 », J=7Hz, 3H0,1.35-1.58 (m, 2H), 1.80-1.95 (m. 2H), 2.50-2.60 (m, Example 167 f2-lsopropv)phcnvl)f2-nitro-4-f £~-ff4-eihoxvcarbonvlpipcra7in-l-vlkarbonv])erhejiv]^ phcnvl1 sulfide Prepared according to the procedures of Example 71, giving a yellow solid. 'II NMR (DMSO-d., 300MHz) 8 1.14 (d, J = 7.0 Hz. 6H); 1.19 (t, J = 7.0H?n 3H); 3.30-3.40 (m, 1H); 3.30-3.73 (br m, 8H); 4.06 (q. J - 7.0 Hz, 2H); 6.64 (d, J = 8.5 Hz, 1H); 7.32-7.63 (m, 6H); 7.90 (dd, J = 8.8,1.8 Hz, 1H); 8.65 (d. J= 1.8 Hz, 1H). MS Example 169 f2-IsopropvlphenvM2-nitro-4-( E-«4-i5obuioxvcarbonvlpiperazm-l- yllcarbonvlleihenvn phenyl] sulfide Prepared according to the procedures of Example 71, giving a yellow solid. 'II NMR (DMSO-4, 300MHz) S 0.90 [d, J - 6.6 Hz, 6H); 1.14 (d, J = 7.0 Hz, 6H); 1.88 (hept, J - 6.6 Hz, 1H); 3.30-3.40 (m, 1H); 3.30-3.73 (br m, 8H); 3.81 (A J - 6.3 Hz, 2H); 6.64 (d, J = 8.5 Hz, 1H); 7.32-7.63 (m, 6H); 7.90 (dd, J = 8.5, 1.5 Hz. 1H); 8.65 (d, J » 1.5 Hz, 1H). MS (APCI) (M+H)' al m/z 512. Anal calcd for C^N.S A: C, 63.38; H, 6.50; N, 8.21. Found: C, 63.15; H, 6.55; N, 8.13. Example 171 f2-Isopropvlphcnvh[2-ni!ro-4-f £-(f4-propionvlpipera2in-l-vl>carbonv]>ethenvl) phenvll sulfide Prepared according to the procedures of Example 71, giving a yellow solid. 'H NMR (DMSO-db, 300MHz) 5 1.00 (t, J = 7.3 Hz, 3H); 1.14 (d, J = 7.0 Hz, 6H); 2.35 (q, J = 7.5 Hz, 2H); 3.30-3.40 (m, 1H); 3.41-3.76 (br m, 8H); 6.64 (d, J = 8.5 Ilz, 1H); 7.32-7.63 (m,6H); 7.90 (dd, J = 8.5, 1.5 Hz. 1H); 8.64 (d. J = 1.5 Hz, 1H). MS (APCI) (M+ NHJ- at m/z 485. Anal calcd for C3,H,.N,S,01: C, 64.22; H, 6.25; N, 8.99. Found: C, 64.04; H. 6.44; N, 8.80. Example 172 Example 173 (2-lsopropvlphenvnf2-nitro-4-f £-ff4-methvlaminocarbonvlpiperazin-l- vitoarbonvikthenvll phenyl} sulfide Prepared according to ihe procedures of Example 71. giving-a yellow 5o'd. 'H NMR (DMSO-d,. 300MHz) 5 1.14 (d, J = 6-8 Hz, 6H); 2.58 (d. J = 4.4 Hz. 3H>; 3.30-3.40 Example 174 (2-lsopropvlphenvn[2-nitro-4-( E.((4-(pvrLmidin-2-vnpiperazin-l- vl)carbonv]>ethcnvl) phenyl] sulfide Example ] 76 (2-lsopropylphenvH[2-nilro-4-f £-(f4-fpvrazitie-2-carbonvnpipera2in-l- vhcarbonvl)ethenvl> phenyl] sulfide Prepared according to the procedures of Example 71, giving a yellow solid. !H NMR (DMSO-cL 300MHz) 5 1.14 (d, J = 6.6 Hz, 6H); 3.30-3.40 (m, 1H); 3.28- Example 177 (2-Isopropvlphenvhf2-trifluoromcthv1-4-f E~(i (2-carboxvpyrrol-3-in-1 -vPcarbonvllethenvI) phenyl] sulfide The title compound was prepared according to the procedures of Example 7i. 'H NMR (CDClj, 300 MHz) 6 7.79 (s. 111). 7.68 (d, 1H, J = 15.4 Hz). 7.4B (d. 1H, J = 7.4 Hz), 7.45 (m, 2H), 7.38 (d, 1H, J = 8.3 Hz). 7.23 (m, 1H), 6.80 Example 178 (2-lsoDropy]phenvnf2-nitro-4-f E-( (3-hydroxvmethvl-4-methvlpiperazin-1 ■ vllcarbonyltetrienvtl phenyl] sulfide Prepared according to the procedures of Example 71, giving a yellow solid. •H NMR (DlviSO-d,, 300MHz) 6 1.14 (d, J = 6.8 Hz. 6H); 2.22 (s, 3H); 1.82-4.63 (br m, OH); 330-3.40 (m, IH); 6.62-6,66 (br m, IH); 7.25-7.63 (m, 6H); 7.86-7.92 (brm, IH); 8.57-8.65 (brm, IH). MS (APCI) (M+H)" at m/z 456. Example 179 f2-IsQproPvlol>g"vnf2-trtf1uoromelhvl-4-(£,-(,f(2-carboxvpviTo)-3-in-l- vHcarbonyl)ethenyi) phenyl] sulfide The title compound was prepared according to the procedures of Example 1. 'H NMR (CDClj, 300 MHz) 8 7.79 (s, IH), 7.72 (d, IH. J = 15.5 Hz), 7.49 (d. IH, J = 7.4 Hz). 7.36-7.46 (m, 3H), 7.23 (m, IH), 6.82 (d, IH, J = 8.5 Hz), 6.74 (d. IH, J = 15,4 Hz), 6.00 (br, 2H), 4.48 {br, IH), 4,51 (br, 2H), 3.48 (m, IH). 1.18 (d. 6H, J = 7.0 Hz). MS (ESI) m/z -460, -492, -921. Example 180 (2-IsoprgpYlphenvnr2-trifh]oromcthvl-4-( £-(f Example 183 (2-Isopropvlphenvhf2-nitro-4-( C-((3-carboxamidopioerazin-l-vDcarbonvl1ethenvl> phenyil sulfide Prepared according to the procedures of Example 71, giving a yellow solid. ■H NMR (DMSO-d.. 300MHz} 8 1.14 (d, 3 =7.0 Hz, 6H); 2.50-4.42 (hr m, 7H); 3.30- Example 185 ("2-lsoDropylphenvl>p-nitri>4-f A'-tn.S-diTncthylpiperazin-l-vlkarbonvllethenvH phenyl] sulfide Prepared according to the procedures of Example 71, giving a yellow solid. 'H NMR (DMSO-d„ 300MHz) 5 0.96-1.06 (rn, 6H); 1.14 (d, J = 6.8Hz, 6H); 2.07-4.39 ( br m, 7H); 6.63 (d. J = 8.5 Hz, 111); 7.30-7.63 (m, 6H); 7.92 (dd, J = 8.S, 1.7 Hz, 1H); 8.60(d.J = ].7Hz, 1H). MS (APC1) (M+H)T at m/z 440. Anal caJcd for C.H^N.S.O,: C, 65.58; H, 6.65; N, 9.56. Found: C. 65.36; II, 6.87; N, 9.27. Example 187 f 3 - [2-Methoxy lethox v phen v 1 )-[2-chl oro-4(£-{ f morpho 1 i n- N vDcarbonvllethenvhphenvil sulfide The title compound was prepared according to the procedures of Example 85. 'H-NMR (CDCIj 300 MHz) S 3.45 (s, 3H), 3.65-3.80 (m, 10H), 4.09-4.13 (m. 2H), 5.82 (broad d, J=l5, IH), 6.88 (d. J=9Hz, 1H), 6.87 (dd, J=91Iz. 2Hz. IH), 7.03-7.10 ',m, 2H), 7.20 (d, J=9Hz, 1H>, 7.31 (t, J=8 Hz, 1H), 7,52 (s, 1H), 7.56 (broad d, J=\5, 1H). (2-Bromophenvl)f2-chloro-4-fE-ff4.4'-S-dioxvthiomorphQ]in-l-vl)carbonvl) ethen vhphenv 11 sulfide 4-Methylmorpholine W-oxide (0.0935 g, 0.798 mmol) and 4A molecular sieves (0.0333g) were added to a solution of (2-Bromophenyt)[2-chloro-4-(E-((thiomorpholin-l-yl)carbonyl) elhenyl)phenyl] sulfide (0.1230g, 0.27 mmol; prepared according lo the procedures described in Example 1). After 15 min, tetrapropy [ammonium perruthcnate (0.0058g, 0.0166 mmol) was added and after 4h had elapsed the starting material was consumed by TLC and the crude products were passed through a plug of silica with 5:2 hexane:elhyl acetate-* 9:1 CH,C1,: MeOH. The mixture was then purified by preparative HPLC to provide the title compound Example 189 (2-Bromophcnvn[2-chloro-4-(E-(TJ-carbomethoxvmethvl-N-f3-(pvrrolidin-2-on-l- vHprop-l-vllaminolcarbonvDelhenvhphenvllsulfide Example 189A N-CaTbomethoxvmethvl-N-f3- Methyl bromoacetate (1.35 tnL, 14.3 mmol) was added dropwisc to a solution of 3-aminopropyl-2-pyrrolidinone (2.0 mL, 14.3 mmol) and diisopropyiethylamine (2.7 mL) in CH^Clj. The reaction was stirred for 12h and was then concentrated in vacuo, and carried forward without further purification. Example 189B f2-Bromonhenvnf2-chloro-4- Example 190 f2-Bromophenvnr2-chloro-4-(E-ff4-.S-oxvthiomorpholin-l-vD-2- pvrrolidinonekarhnnvDethenvl)phenvllsulfide The title compound (0.0178g, 14%) was isolated from she same reaction mixture as described in Example J SS. 'H-NMR (DMSO-d6,300MHz) S 8.12 (d, J= 1.8 Hz, 1H). 7.81 (dd, J= 7.9,1.3 Hz, IH), 7.65 (dd, J= 8.3,1.7 Hz, 1H), 7.46 (d,J= 7.4 Hz, IH), 7.26-7.48 (m, 4H), 7.04 (d, J= 7.4 Hz, IH), 4.29 (br m, 2H), 3.97 (br in, IH), 3.61 (br m, IH), 2.80 (brm,4H), MS(APCI) (M+H)" at m/z470.472,474. Example 192 f2-IjopropvIpbcnvl1[2-nitro-4-(g-ff3-acetoxvmethvl)piperazin-l-y1)carbonvi)ethenvl1 phepvl] sulfide Prepared according to the procedures of Example 71, giving a yellow solid. 'H NMR (DMSO-d,, 300MHz) 6 1.14 (d, J = 6.8 Hz, 6H); 2.04 (s, 3H); 3.30-3.40 (m. IH); 2.50-4.46 (br m, 911); 6.64 (d, J = 8.8 Hz, III); 7.30-7.62 (m, 6H); 7.87-7.93 (m. IH); 8.58-8.63 (br m, IH). MS (APC1) (M+H)- at m/z 484. Anal calcd for C„HSN,SA 0.2H,O: C, 61.60; H, 6.09; N. 8.62. Found: C, 61.63; H, 6.21; N, 8.41. Example 193 f2-Isopropv]phenvnf2-nilro-4-f £-f(3.5-dimethvl-4acetylpjperazui-l- vncarbonvDethenvn phenyl) sulfide Prepared according to the procedures of Example 71, giving a yellow solid. Example 194 l'l-Me[hvlindol-5-vli[2-chlorQ-4-(£-(-l,4-acelvlpiperazin-l-vl'lcarbonvlklhenvl) phenyl) sulfide The title compound was prepared by the procedures described in Example 85, substituting 5-todoindole with A'-methyl-S-bromoindole, giving a white solid. 'H Example 195 ienzodioxan-$-v^R'"'tro-^-f^--'f4-aceivlpiperazin-l-vl1carbonvi1ethenY[) phenyl] sulfide Example 195 A 6-Mercaptobenzodi oxane The title compound was prepared by the procedures described in Example 'A, substituting 2-ethoxybenzene with 6-iodobenzenedroxane. Example 195B Benzodioxan-6-vl>l2-nitro-4-i'£-((4-acetvlpipera7.in-l-v]karbonvnetbenvn phenvll sulfide The title compound was prepared by the procedures described in Example 32, ibstituting 2,4-dichlorobenzenethiol with 6-mercaptobenzcnedioxane, to give a lighl- Example 196 fBenzodioxan-6-vllf 2-nitro-4-f E-f (3-f pyrrolidin-2-on-1 - vhprop-1 -vlaminojcarbonyl) ethen vi)phen vl Isti I Fide The title compound was prepared by the procedures described in Example 32, substituting 2,4-dichlorobenzenethiol with 6-mercaptobenzenedioxane, and 1 -acetylpiperazinc with 3-amLnopropyl-l-pyrrolidin-2-one, giving a light-yellow solid. 'H NMR (d'-DMSO, 300 MHz) 5 1.64 (p, J = 7.2 Hz, 2H), 1.92 (p. J - 7.8 Hz. 2H), Example 197 (Benzodioxan-6-vl1[2-nitro-4-( £-((3-carboethoxvpiperidin-1 -ylt carbonvl'tetherivj) phenyl] sulfide The title compound was prepared by the procedures described in Example 196 substituting N-(3'-aminopropyl)-2-pyrrolidinone wiih ethyl nipecotale, giving a Example 198 (Bcnzodioxan-e-vPf 2-nitro-4-( £-(Y4-carboethoxvDiperidin-1 -vO carbonvnethenvB phenyl! sulfide The title compound was prepared by the procedure described as in example 196 substituting N-(3'-aminopropyl)-2-pyrrolidinone with ethyl isonipecotate, giving Example 199 r2-Ethoxvphenvl')r2-trifluoromethvl-4-fZ-f(4-acetv]pipcra2in-l-vl)carbonvnethenvl') phenvll sulfide Example 199A (,2-Ethoxvphenvl'>[2-trifluoromethvl-4-(Z-((4-carbomelhoxvethenvl') phenvll sulfide Bis-(2,2,2-trifluoroethyl)(methoxycarbonylmcthyl)phosphonate (1.20 g, 3.77 mmole), and 18-crown-6 (3.56 g, 13.48 mmol) were dissolved in 22 ml of dry THF. The mixture was cooled to -78 °C and KN(SiMe3)2 (0.5 M in THF, 4.04 mmol) was added and stirred for 30 min. (2-Ethoxyphenyl)[2-trifluoromethyl-4-formyl phenyl] I sulfide (1.10 g, 3.77 mmol, prepared according to the procedure of example 1) in 13 ml of THF was added via cannulation. After 1 hr at that temperature, the cooling bath was removed and the mixture allowed to warm to ambient temperature. Saturated NH4C1 soln. was added and the mixture was extracted with ethyl acetate three times. The combined organics were dried over sodium sulfate, concentrated in vacuo and i purified by medium pressure chromatography on silica gel to give 772 mg (60% yield) of the cis- isomer (J0i,nnil. = 12.5 Hz) along with 322 mg (25% yield) of the trans- isomer (J„lcnilic = 12.5 Hz). Example 199B (2-Ethoxvphenvnr2-trifluoromethvl-4-(Z-((4-acetvlpiperazin-l-vl)carbonvDethcnvl) phenyl! sulfide The compound of Example 199 A was converted to the corresponding amide according to the procedures of Example 1. 'H NMR (CDC1}. 300 MHz) 5 7.64 (d, 1H, Example 200 (2-Eftoxvphenvl¥2-trifluoromethyl-4-(£-((6-methvlpvrid-2-vlaminokarbonvltethenvD phenyl! sulfide The title compound was prepared according to the procedures of Example 1. 'H NMR (CDC1,, 300 MHz) 6 8.12 (d, 1H, J = 8.1 Hz), 7.78 (s, 1H, J = 1.7 Hz), 7.70 Example 201 (2-Methvl-3-chlorophenvn[2-nitro-4-(£-ff4-acetvlDiDerazin-l-vl>carbonvlkthenvn phenyl! sulfide The title compound was prepared according to the procedures of Example 1. Example 202 fBenzodioxan^-vllte-nitro^-f E-((3-carboxamidoniperidin-1 -vll carbonvltethenvO phenyl! sulfide The title compound was prepared by the procedures described in Example 196, substituting N-(3'-aminopropyl)-2-pyrrolidinone with nipecotamide, giving a Might yellow solid, mp 243-245 °C. 'H NMR (CDC1„ 500 MHz) 8 1.38-1.50 (m, 2H), 1.77- Example 203 (Benzodioxan-e-vDp-nitKM-f g-(f2-carboethoxvpiperidin- 1-vO carboBvOethenyl) phenvll sulfide The title compound was prepared by the procedures described in Example 196, ubstituting N-(3'-aminopropyl)-2-pyrrolidinone with ethyl pipecolinate, producing a ight yellow solid, mp 74-75 °C.' H NMR (CDC13,300 MHz) d 1.28 (t, J=7.0 Hz, Example 204 (,Benzodioxan-6-vnf2-nitro-4-(£'-((4-carboxamidopipcridin-l-vl) carbonvDethenvO phenvll sulfide The title compound was prepared by the procedures described in Example 196, substituting N-(3'-aminopropyl)-2-pyrrolidinone with isonipecotamide, giving a light yellow solid, mp>230°C. 'H NMR (CDC1,, 500 MHz) 8 1.35 (m. 1H), 1.60 (m, 1H), 1.72(m, 1H), 1.68 (m, lH),2.20(m, lH),2.75(m, 1H), 3.04 (m, lH),3.20(m, 1H), Example 205 (Benzodioxan-6-vDf2-nitro-4-f E-((4-/e/7-buloxvcarbonvlpiperazin-1 -vl) carbonvDethenvll phenvll sulfide The title compound was prepared by the procedures described in Example 196, substituting N-(3'-aminopropyl)-2-pyrrolidinone with Boc-piperazine, giving a light yellow solid, mp 165-167 °C. 'H NMR (CDC13, 300 MHz) 5 1.48 (s, Example 206 C 2-Isopropvlphenvnr2-nitro-4-r £-((.Tvn-3.5-dimethvlmorpholin-1 -vBcarbonvllethcnvn phenyl^ sulfide Prepared according to the procedures of Example 71, giving a yellow solid. Example 207 (2-Isopropvlphenvl')[2-nitro-4-(£-((tw/f'-3.5-dimethvlmorpholin-l-vl)carbonvltethenvn phenyl! sulfide Prepared according to the procedures of Example 71, giving a yellow solid. Example 208 (2-Isopropvlphcnvnr2-nitro-4-(£-((3-carboethoxvpiperazin-l-vl')carbonvl'>ethenvl) phenvll sulfide Prepared according to the procedures of Example 71, giving a yellow solid. •H NMR (DMSO-d* 300MHz) 5 1.14 (d, J = 6.8 Hz, 6H); 1.08-1.26 (m, 3H); 2.52- Example 209 (2-Isopropvlphenvl')r2-nitro-4-(' E-(( 3-isopropoxvcarbonvlpiperazin-1 - vlkarbonvllethenvP phenvll sulfide Prepared according to the procedures of Example 71, giving a yellow solid. Example 210 C2-Isopropvlphenvl)f2-nitro-4- Example 211 (2-Isopropvlphenvn[2-nitro-4-('£-((3-carbomethoxv-4-hvdroxvpiperidin-l- vPcarbonvPethenvl') phenyl] sulfide Prepared according to the procedures of Example 71, giving a- yellow solid. 'H NMR (DMSO-d,, 300MHz) 8 1.14 (d, J = 7.0 Hz, 6H); 1.59-1.75 (br m, 211); 2.50- Example212 (2-lsopropvlphenvPf2-nitro-4-( E-((3-hvdroxvmethvl-4-hvdroxvDiperidin-1 - vncarbonynethenvn phenyl] sulfide Prepared according to the procedures of Example 71, giving a yellow solid. 'H NMR (DMSO-d6,300MHz) o 1.14 (d, J = 6.8 Hz, 6H); 1.49-1.90 (br m, 2H); 2.75- Examplc213 (2-Ethoxvphenvnr2-trifluoTomethvl-4-(£-((2-carbomethoxv-4-(methoxvcarbonvPpiperazin-l-vncarbonvl)ethenvD phenvll sulfide The title compound was prepared according to the procedures of Example 71. Example 214 Q-EthoxvphenvUf 2-trifluoromethvl-4-( £-((2-carbomethoxv-4-methvl piperazin-1 -vlkarbonvltethenvl') phenvll sulfide The title compound was prepared according to the procedures of Example 71. Example 215 f2-Ethoxvphenvnf2-trifluoromethvl-4-( £-f('2-carboxv-4-(methoxvcarbonvl')piperazin-1 -vDcarbonvDethenvD phenyl! sulfide The title compound was prepared according to the procedures of Example 71. Example 216 nndol-6-vPf2-chloro-4-( fi-(f4-acctvlpiperazin-l-vl")carbonvnelhenyP phenvll sulfide The title compound was prepared by the procedures described in Example 85, substituting 5-iodoindole with 6-bromoindole, isolated as a white solid. 'H NMR (d6- Example 217 (l-Ethvl.3-(,dimethYlaminoniethvnindol-7-vl'>[2-chloro-4-(,£-(('4-acetvlpiperazin-l-vDcarbonvPethenvP phenyl] sulfide The title compound was prepared by the procedures described in Example 85, substituting 5-iodoindole with 7-bromo-3-^,A^-dimethylmethyl-A',-ethyl indole, and isolated as a light-brown solid. 'H NMR (CDC1,, 300 MHz) 6 1.30 (t, J = 7.05 Hz, Example 218 f5-Ethoxvbenzodioxan-6-vPf2-chloro-4-( E-((4-acetvlpiperazin-1 -vPcarbonvPethenvP phenvll sulfide The title compound was prepared by the procedures described in Example 85, substituting 5-iodoindole with 6-bromo-5-ethoxybenzodioxane. as s white solid. 'H Example 219 (2-Ethvl-4-bromophenvDr2-nitro-4-(£-(Y4-acetvlpiperazin-l-vlkarbonvl)ethenvl') phenyl! sulfide The title compound was prepared according to the procedures of Example 32. Example 220 f Benzodioxan-6-vDr2-nitro-4-( £-((2-carboxvpiperidin-1 -vl) carbonvDethenvO phenyl] sulfide The title compound was prepared by the hydrolysis of the compound of Example 203 under basic conditions (aq. NaOH/EtOII), producing a light yellow solid:, mpl 65 °C(dcc). 'H NMR (DMSO-d,, 300 MHz) 5 1.15-1.52 (m, 3H), 1.46- Hz, 1H), 7.73 (m, 1H), 8.52 (m, 1H). MS (ESI) m/z469 (M-H)+, 471 (M+H)\ Anal, calcd. for CMH2lN207SNa 'NaOH«2.7 H,0: C, 47.54; H, 4.75; N, 4.82. Found: C, 47.18; H, 4.36; N, 4.89. Example 221 fBenzodioxan-6-vlW2-nitro-4-(£-(f4-carboxvmethvlpirjerazin-l-vl)carbonvDethenvD phenvll sulfide The title compound was prepared by deprotection of the compound 33 with TFA in CH2C12. The resultant free amine was treated with tert-b\ity\ bromoacetate and TEA in acetonitrile at room temperature, and followed by deprotection with TFA in CH2C12! giving a light solid, mp 120 °C (dec). 'H NMR (DMSO-d,, 300 MHz) 8 3.20-3.45 (m, 4H), 4.20 (s, 2H), 3.50-3.80 (m, 4H), 4.28-4.46 (m, 4H), 6.86 (d, J=8.5 Hz, 1H), 7.04 (m, J=8.0 Hz, 1H), 7.09 (dd, J=2.0 8.0 Hz, 1H), 7.15 (d, J=2.0 Hz, 1H), 7.40 (d, J=15.5 Hz, 1H), 7.56 (d, J=15.0 Hz, 1H), 7.90 (dd, J=2.0, 8.5 Hz, 1H), 8.63 (m, 1H). MS (ESI) m/z 484 (M-H)\ 486 (M+HV\ Calcd. Anal for C23H2,N107S'1.19CF3COOH'1.34 H30: 47.63; H, 4.11; N, 6.89. Found: C, 47.93; H, 4.51;N, 6.49. Example 222 (3-Morpholinophenvn[2-nitro-4-(£-((4-acetvlpiperazin-l-vl)carbonvl')ethenvl') phenvll sulfide The title compound was prepared according to the procedures of Example 62, employing the compound of Example 103 as starting material. 'H NMR (CDC13,300 MHz) 5 7.80 (s, IH), 7.64 (d, IH, J = 15.4 Hz), 7.43 (m, IH), 7.32 (t, IH, J = 8.1 Hz), 7.08 (m, 2H), 6.99 (m, 2H), 6.84 (d, IH, J = 15.4 Hz), 3.87 (t, 4H, J = 4.8 Hz), 3.63-l 3.79 (m, 6H), 3.50-3.55 (m, 2H), 3.18 (t, 4H, J = 4.8 Hz), 2.10 (s, 3H). MS (ESI) m/z 520,542,1061. Example 223 (5-Ethoxvbenzodioxan-8-vnf2-chloro-4-( £-((4-acetvlpiperazin-l -vlkarbonvPethenvl) phenyl] sulfide The title compound was prepared by the procedures described in Example 85, substituting 5-iodoindole with 8-bromo-5-elhoxybenzodioxane, giving a white solid. 'H NMR (CDC1„ 300 MHz) 8 1.52 (t, J= 7.2 Hz, 3H), 2.15 (s, 3H), 3.48-3.59 (m, 2H), 3.59-3.85 (m, 6H), 4.16 (q,J= 7.2 Hz, 2H), 4.22-4.30 (m, 2H), 4.30-4.40 (m, 2H), 6.59 (d, J= 8.7 Hz, IH), 6.63 (d,y= 8.7 Hz, IH), 6.78 (d, J= 15.6 Hz, IH), 7.08 (d,J=8.7Hz, 1H), 7.17 (dd, J =2.1,8.7 Hz, IH), 7.51 (d,J=2A Hz, IH), 7.58(d,./ = 15.6 Hz, IH). MS (APCI+) (M+H)" at m/z 503, 505. Example 224 (5-Chloro-8-emoxvquinolin-7-vlM2-chloro-4-(.ff- vDcarbonvPethenvD phenyl! sulfide The title compound was prepared by the procedures described in Example 85, substituting 5-iodoindole with 5-chloro-8-ethoxy-7-iodoquinoline, giving a white solid. 'H NMR (d6-DMSO, 300 MHz) 6 1.37 (t, J= 7.2 Hz, 3H), 2.04 (s, 3H), 3.41-3.82 (m, 8H), 4.46 (q, J = 7.2 Hz, 2H), 7.29 (s, IH), 7.37 (d, J = 8.4 Hz, IH), 7.42 (d, 7= 15.6 Hz, IH), 7.51 (d,J= 15.6 Hz, 1H),7.68 (dd, J= 1.8,8.4 Hz, IH), 7.74 (dd,./ = 3.9, 8.4 Hz, IH), 8.15 (s, IH), 8.55 (dd, J- 1.8, 8.4 Hz, IH), 9.05 (dd, J= 1.8, 3.9 Hz, IH). MS (APCI1) (M+H)+ at m/z 530, 532,534. Example 225 (2-Isopropvlphenvl)r2-nitro-4-f JT-fO-carboethoxvpiperidin-l-vlkarbonyllethenvl) phenyl] sulfide Example 225A (2-Isopropvlphenvn[2-nitro-4-( g-fcarboxvlethenvO phenyl! sulfide To a stirred mixture of 4-chloro-3-nitrocinnamic acid (500 mg, 2.2 mmol) in 5 mL of anhydrous DMF with K2C03 (91 lmg, 6.6 mmol) was added 2-isopropylbenzenethiol (372 mL, 2.2 mmol) in 1 mL of DMF dropwise. The resulting mixture was then heated at 70 °C under nitrogen atmosphere over night. Water (25 mL) was then added and the reaction mixture was acidified to pH = 4 with 3N HC1. The cloudy mixture was extracted with EtOAc (2x20 mL). The combined organic layer was washed with brine, dried over Na2SO title compound as viscous light-yellow oil, which was used for coupling with further purification. Example 225B (2-Isopropvlphenvl')f2-nitro-4-( £-((3-carboethoxvpiperidin-1 -vDcarbonvltethenvP phenyl! sulfide The title compound was prepared by the procedures described in Example 92, substituting the benzoic acid with cinnamic acid from 225A, and ammonium chloride with ethyl nipecotate, giving a light-yellow solid. 'IINMR (CDC13, 300 MHz) 5 1.18 i (d, J= 6.6 Hz, 6H), 1.27 (1,7= 7.2 Hz, 3H), 1.69-1.82 (m, IH), 1.82-1.99 (m, IH), 1.99-2.20 (m, IH), 2.45-2.62 (m, 2H), 3.45 (septet, ./= 6.6 Hz, IH), 3.56-3.80 (m, IH), 3.80-4.10 (m, 2H), 4.16 (q, J = 7.2 Hz, 2H), 4.65-4.81 (m, IH), 6.69 (d, J = 8.4 Hz, lH),7.00(brs, IH). 7.31 (dd, J =2.4, 6.9 Hz, IH), 7.42 (brd,.7=8.4 Hz, IH), 7.51 (d, J = 15.6 Hz, IH), 7.52 (overlapping d, 2H), 7.58 (d, J = 15.6 Hz, IH), 8.43 (s, i 1H). MS (APCr) (M+H)- at m/z 483. Example 226 (2-Isoproovlphenvl)f2-nitro-4-f E-fO-carboxvpiperidin-l-vDcarbonvDethenvP phenyl! sulfide I The title compound was prepared by the procedures described in Example 155, substituting the ethyl ester from Example 137 with the ethyl ester from Example 225B, and KOH with NaOII, to give a light-yellow solid. 'H NMR (d6-DMSO, 300 MHz)S 1.15 (d, J" 6.9 Hz, 6H), 1.30-1.50 (m, IH), 1.50-1.80(m, 2H), 1.88-2.04 (m, 2H), 2.95-3.17 (m, IH), 3.94-4.06 (m, IH), 4.06-4.22 (m, 2H), 4.40-4.52 (m, IH), 6.63 (d, J= 8.7 Hz, IH), 7.33-7.53 (m, 3H), 7.56-7.68 (m, 3H), 7.91 (dd, /= 1.8, 8.4 Hz, IH), 8.63 (d, J= 8.4 Hz, IH). MS (APC1+) (M+HT at m/z 455. Example 227 C2-Isopropvlphenvl)r2-nitro-4-(£-(f(3-ethanesulfonvlaminocarbonvnpiperidin-l-vl)carbonvl)ethenvl) phenvll sulfide To a stirred solution of free acid (50 mg, 0.11 mmol) from Example 226 in 1 mL of methylene chloride was added ethyl sulfonamide (18 mg, 0.17 mmol), ED AC (25 mg, 0.13 mmol), and DAMP (2.7 mg, 0.022 mmol) sequentially. The mixture was stirred at ambient temperature for 16 h. The solvent was then removed on a rotavap under reduced pressure and the residue was purified on an Alltech sep-pak, eluting with 1 % MeOH in EtOAc to give 30 mg (50 % yield) the title compound as a light yellow solid. 'H NMR (CDC13, 300 MHz) S 1.18 (d,./ = 6.3 Hz, 6H), 1.34 (t, J = 7.5 Hz, 3H), 1.61-1.74 (m, 2H), 1.84-2.04 (m, IH), 2.13-2.35 (m, IH), 2.60-2.75 (m, 2H), 3.44 (p,y= 7.5 Hz, 2H), 3.53-3.66 (m, IH), 3.66-3.85 (m. 211), 4.00-4.18 (m, IH), 6.71 (d, J =8.7 Hz, lH),6.88(d,7= 15.6 Hz, IH), 7.31 (dd, J = 2.4, 8.4 Hz, 1H),7.41 (d, J= 1.8, 8.4Hz, IH), 7.51 (d,7= 1.8 Hz, IH), 7.54(d,J = 8.4 Hz, III), 7.67 (d,./= 15.6 Hz, IH), 8.43 (s, IH). MS (ESI+) (M+liy at m/z 546. Example 228 (2-IsoDropvlphenvDf2-nitro-4-f E-ffl3-(4-methvIpipera2ine) sulfonylaminocarbonvDpiperidin-l-yDcarbonvl'tethenyl) phenyl! sulfide The title compound was prepared by the procedures described in Example 228, substituting ethyl sulfonamide with JV-methylpiperazine sulfonamide, giving a light yellow solid. 'HNMR^DCI,, 300MHz)5 1.18(d, J=6.5 Hz,6H), 1.40-2.10(m, 9H), 2.60 (s, 3H), 2.60-2.76 (m, 4H), 2.90 (br s, 3H), 3.44 (septet, J= 6.5 Hz, IH), 3.52-4.08 (m, 4H), 6.71 (d, J= 8.4 Hz, IH), 6.95 (d,J= 15.6 Hz, IH), 7.31 (d,J = 2.1, 8.4 Hz, IH), 7.43-7.57 (m, 411), 7.64 (d,J= 15.6 Hz, IH), 8.44 (s, IH). MS (ESP) (M+H)* at m/z 616. Anal. Calcd for C29H37N5O6S2 -1.13 H2O: C, 54.76; H, 6.22; N, 11.01. Found: C, 54.78; H, 6.11; N, 10.87. Example 229 f2-Isopropvlphenvl)f2-nitro-4- Example 230 f2-Isopropvlphenvnf2-nitro-4-( £-((3-methvl-4-acetvlpiperazin-l - vltearbonvnethenvD phenyl^ sulfide Prepared according to the procedures of Example 71, giving a yellow solid. 'H NMR (DMSO-d,, 300MHi) 8 0.94-1.18 (m, 3H); 1.14 (d, J = 7.0 Hz, 6H); 1.98- 2.08 (br m, 3H); 2.69-3.74 (br m, 4H); 4.02-4.65 (br m, 4H); 6.64 (d, J = 8.5 Hz, IH); 7.31-7.63 (m, 6H); 7.88-7.96 (br m, IH); 8.65 (br s, 111). MS (APCl) (M+H)' at m/z 468. Anal calcd for C„HNN,S,0,0.1^0: c, 63.91; H, 6.70; N, 8.94. Found: C, 63.54; H, 6.41; N, 8.67. Example 231 (2-Hvdroxvphenvn-|'2-chloro-4f£-r(morpholin-l-vlkarhonvnethenvl)phenvnsulfide The title compound was prepared according to the procedures of Example 1, giving a white solid, m.p. 157-158C. 'H-NMR (CDC13 300 MHz) 6 3.60-3.76 (m, 8H), 6.42 (s, IH), 6.57 (d, J=9hz, IH), 6.76 (d, J=15Hz, IH), 6.99-7.04 (m, IH), 7.10-7.20 (m, 2H), 7.42-7.55 (m, 4H). Anal. Calcd. for C^HuClNOjS: C, 60.71; h, 4.83; N, 3.73. Found: C, 60.48; H, 5.05; N, 3.69. Example 232 ( 1 -(Carboxvmethvl)indol-5-vJ)f2-chloro-4-( £-((4-acetvlpiperazin-l - vncarbonvltethenyl) phenyl) sulfide To a stirred solution of indole compound from Example 85 (35 mg, 0.080 umol) in 1 mL of anhydrous DMSO was added crushed KOII (18 mg, 0.32 mmol). \fter 45 min, f-butyl bromoacetate (23.5 mL, 0.16 mmol) was added. The resulting nixture was stirred at ambient temperature for 10 h. Water was men added and the reaction mixture was acidified with 3 N HC1 to pH = 3. The title compound (25 mg, 53 %) was collected through filtration and dried in vacuum oven, giving a white solid. H NMR (d'-DMSO, 300 MHz) 5 2.04 (s, 3H), 3.38-3.80 (m, 8H), 4.59 (s, 2H), 6.45 [d, J= 3.0 HA 1H), 6.52 (d, J = 8.7 HA 1H), 7.21 (dd, J = 2.1,8.7 HA 1H), 7.25 (d, J = 15.6 Hz, 1H), 7.38 (d, J= 15.6 HA 1H), 7.40 (d,J= 3.0 Hz, 1H), 7.47 (d, J= 8.4 HA 1H), 7.80 (d,J= 2.1 HA lH),7.97(s, 1H). MS (ESO(M-II)' at m/z 496,498. Example 233 (Benzodioxan-6-v0f2-trifluoromethvl-4-( /T-(Y4-acetvlpiperazin-l-vDcarbonvOethenvP phenvl) sulfide The title compound was prepared by the procedures described in Example 84, substituting 2-bromothiophenol with 6-mercaptobenzenedioxane. white solid; 'H NMR (CDClj, 300 MHz) 8 2.15 (s, 3H), 3.46-3.89 (m, 8H), 4.30 (dd, 7= 2.1, 6.0 HA *H), 6.84 (d, J= 15.0 HA 1H), 6.92 (d, J= 8.4 Hz, III), 6.97-7.10 (m, 3H), 7.42 (d, J = 8.4 HA 1H), 7.64 (d, J= 15.0 HA 1H), 7.77 (s, 1H). MS (ESF) m/z 493 (M+H)'. Example 234 f2-lsopropvlphenvnr2-nitro-4-(£'-f(3-n-Dvrrolidin-2-onvl')prop-l-vlamino) carbonvltethenvD phenyl] sulfide Prepared according to the procedures of Example 71, giving a yellow solid. 'H NMR(DMSO-d,,300MHz)5 1.14 (d, J = 7.1 Hz,6H); 1.58-1.68(m,2H); 1.85-1.97 [m, 2H); 2.18-2.24 (m,2H); 3.10-3.22 (m, 4H); 3.30-3.39 (m, 3H); 6.65-6.72 (m, 2H); 7.32-7.45 (m, 2H); 7.57-7.62 (m, 3H); 7.76 (dd, J = 8.8,2.0 Hz, IH); 8.11-8.17 (m, IH); 8.44 (d, J = 2.0 Hz, IH). MS (APCI) (M+H)' at m/z 468. Anal calcd for ^H^S.OvO^eCHjCOOCHjCH,: C, 63.77; H, 6.39; N, 8.57. Found: C, 63.46; H, 5.37; N, 8.90. Example 235 G-(7-MorphoIinoethylamino)phenvl)[2-trifluoromethvl-4-(E-((4-acetvlpiperazin-l-vllcarbonvllethenvl'l phenyl! sulfide The title compound was prepared according to the procedures of Example 62, mploying the compound of Example 103 as starting material. 'H NMR (CDC13,300 AHz) 8 7.78 (d, IH, J = 1.4 Hz), 7.64 (d, IH, J = 15.4 Hz), 7.42 (d, IH, J = 8.8 Hz), '.21 (t, IH, J = 7.9 Hz), 7.12 (d, IH, J = 8.5 Hz), 6.84 (d, IH, J = 15.4 Hz), 6.82 (m, H), 6.76 (t, IH, J = 1.8 Hz), 6.66 (m, IH), 3.72 (m, 10H), 3.51-3.55 (m, 2H), 3.16 (t, H, J = 5.9 Hz), 2.64 (t, 2H, J = 5.9 Hz), 2.50 (m, 4H), 2.15 (s, 3H). MS (ESI) m/z 63. Example 236 (2-Pvnolidin-l-vIphenvnf2-nitro-4-(g-((4-acetvlpipeTazin-l-vlkarbonvl)ethenvl> phenyl] sulfide The title compound was prepared according to the procedures of Example 62, employing the compound of Example 103 as starting material. 'H NMR (CDC13,300 MHz) S 7.77 (s, IH), 7.64 (d, IH, J = 15.4 Hz), 7.40 (m, IH), 7.22 (d, IH, J = 7.8 Hz), 7.10 (d, IH, J = 8.8 Hz), 6.82 (d, IH, J = 15.3 Hz), 6.76 (d, IH, J = 7.8 Hz), 6.70 (t, IH, J = 2.0 Hz), 6.59 (dd, IH, J = 2.4, 8.1 Hz), 3.61-3.79 (m, 6H), 3.51-3.54 (m, 2H), 3.28 (m, 4H), 2.14 (s, 3H), 2.01 (m, 4H). MS (ESI) m/z 504. Example 237 n-Bromophenvn^-nitro^-Cg-Cn-carboethoxvpyrrolidin-l-vncarbonVDethenvl) phenyl] sulfide The title compound was prepared according to the procedures of Example 1. 'H NMR(CDC1„ 300 MHz) 8 8.40 (d, IH. J = 1.5 Hz), 7.75 (m, IH), 7.45 (m, IH), 7.48-7.56 (m, 2H), 7.38 (t, IH, J - 7.9 Hz), 7.00 (br, IH), 6.87 (d, IH, J = 9.5 Hz), 4.16 (q, 2H, J = 7.1 Hz), 3.99 (br, 2H), 3.70 (br, IH), 3.30 (br, IH), 3.00 (br, IH), 2.55 (s, IH), 2.10 (m, IH), 1.89 (br, IH), 1.85 (br, IH), 1.27 (t, 3H, J = 7.0 Hz). MS (ESI) m/z 519,521. Anal. Calcd for C23H23BrN205S 0.19 H20: C, 52.84; H, 4.51;N, 5.36. Found: C, 52.85; H, 4.55; N, 5.28. Example 238 (3-Bromophenvnr2-nitro-4-(,£-('('4-carboethoxvDvrrolidin-l-vl)carbonvl1ethenvn phenvll sulfide The title compound was prepared according to the procedures of Example 1. 'H NMR (CDC13) 300 MHz) 8 8.41 (s, IH), 7.75 (m, IH), 7.62-7.67 (m, 2H), 7.53 (m, IH), 7.48 (d, IH, J = 8.8 Hz), 7.38 (t, IH, J = 7.9 Hz), 6.98 (br, IH), 6.88 (d, IH, J = 8.5 Hz), 4.18 (q, 2H, J = 7.1 Hz), 3.64-78 (br, 4H), 3.55 (br, 4H), 1.29 (t, 3H, J = 7.0 Hz). MS (ESI) m/z 520,522. Example 239 (2-(Hvdroxvmethvl)-benzodioxan-6-vl)f2-chloro-4-f £-((4-acetvlpiperazin-l-vDcarbonvl)ethenvI) phenyl] sulfide The title compound was prepared by the procedures described in Example 85, substituting 5-iodoindole with a mixture of 2-hydroxymethyl-6-bromobenzodioxane and 2-hydroxymethyI-7-bromobenzodioxane, giving a white solid. 'H NMR (CDC13, 300 MHz, mixture of 3:2 regioisomers) 5 2.15 (s, 3H), 3.46-3.83 (m, 8H), 3.83-4.01 (m, 2H), 4.10-4.42 (m, 4H), 6.75 (d,J= 8.4 Hz, IH), 6.79 (d,J= 15.9 Hz, IH), [6.95 (d), 6.98 (d), ./= 4.8 Hz, IH in total], [7.04 (t), 7.07 (t), J= 1.5 Hz, IH in total], [7.10 (d), 7.11 (d), J= 2.4 Hz, IH in total], 7.19 (d, ./= 8.4 Hz, IH), 7.53 (s, IH), 7.58 (d, J = 15.6 Hz, IH). MS (APC1*) (M+H)* at m/z 489. Example 240 (Benzodioxan-6-vnr2-trifluoromethvl-4-(E-(f3-(pvrrolidin-2-on-l-vnDroD-l-vlaminokarbonvlt ethenyPphenvllsulfide The title compound was prepared by the procedures described in Example 233, substituting l-acetylpiperazine with 3-aminopropyl-l-pyrrolidin-2-one, giving a white solid. 'H NMR (CDC13,300 MHz) 6 1.69-1.80 (m, 2H), 2.08 (p, J= 7.5 Hz, 2H), 2.44 (t, J= 7.5 Hz, 2H), 3.27-3.48 (m, 6H), 4.24-4.34 (m, 4H), 6.44 (d, J= 15.6 Hz, 1H), 6.90 (d, J = 8.4 Hz, III), 7.00 (d, J= 8.4 Hz, 1H), 7.01 (dd, J= 2.7, 8.4 Hz, 1H), 7.06 (d, J = 2.7 Hz, 1H), 7.08 (s, 1H), 7.40 (dd, 7= 2.1, 8.4 Hz, 1H), 7.53 (d, J= 15.6 Hz, 1H), 7.75 (d, ./= 2.1 Hz, 1H). MS (ESF) (M+H)* at m/z 507. Example 241 (3-(Dimemvlaminomcthv0indol-5-vl¥2f(4-acetvlpiperazin-l-vPcarbonvl'tethenvl) phenyl] sulfide The title compound was prepared by the procedures described in Example 217, substituting the indole from 186 with the indole from Example 85, resulting in a white solid. 'H NMR (CDCl,, 300 MHz) S 2.15 (s, 3H), 2.54 (s, 6H), 3.47-3.85 (m, 8H), 4.05 (s, 2H), 6.56 (d,y= 8.7 Hz, 1H), 6.77 (d, J= 15.6 Hz, 1H), 7.09 (d, 7= 8.7 Hz, 1H), 7.36 (dd, J= 1.5, 8.7 Hz, 1H), 7.50 (d,./= 8.7 Hz, 1H), 7.52 (s, 2H), 7.56 (d,J = 15.6 Hz, 1H),7.88 (s, 1H), 9.27 (s, 1H). MS (ESI+) (M+H)4 at m/z 497,499. Anal. Calcd for C26H29CIN4O2S ■ 0.46 TFA • 1.72 MeOH: C, 56.89; H, 6.06; N, 9.27. Found: C, 56.83; H, 6.15; N, 9.46. Example 242 f2-IsopropvlDhenvn[2-rutro-4-(£-((2-carboethoxvpiperidin-l-vlkarbonvnethenvl) phenyl! sulfide The title compound was prepared by the procedures described in Example 225, substituting ethyl nipecotate with ethyl pipecolinate, giving a light-yellow solid. 'H NMR(CDCl3,300MHz)5 l.I8(d,./=6.9Hz,6H), 1.28 (t, J =7.35 Hz, 3H), 1.34-1.62 (m, 2H), 1.62-1.84 (m, 3H), 2.32 (br d,J= 13.2 Hz, IH), 3.33-3.54 (m, IH), 3.45 (septet, ./= 6.9 Hz, IH), 3.99 (br d, J= 13.2 Hz, IH), 4.21 (q, J= 7.35 Hz, 2H), 5.46 (br s, IH), 6.69 (d, J= 8.7 Hz, IH), 7.01 (d, J= 15.6 Hz, IH), 7.25-7.34 (m, IH), 7.42 (d, ./= 8.7 Hz, IH), 7.46-7.60 (m, 3H), 7.58 (d,J= 15.6 Hz, IH), 8.44 (s, IH). MS (ESr)(M+H)-atm/z483. Example 243 (2-Isop:ropvlphenvnf2-nitro-4-( g-fQ-carboxvnineridin-l-vBcarbonvUethenvn phenyl | sulfide The title compound was prepared by the procedures described in Example 226, substituting the ethyl ester from Example 225 with the ethyl ester from Example 242, giving a light-yellow solid. 'H NMR (CDC]3,300 MHz) 8 1.18 (d, J= 6.9 Hz, 6H), 1.40-1.89 (m,5H), 2.34 (brd,y= 11.7 Hz, IH), 3.31-3.51 (m, IH), 3.44 (septet,./ = 6.9 Hz, 1H),4.01 (d,J= 11.7 Hz, IH), 5.42 (brs, lH),6.70(d, .7=7.8 Hz, 1H),6.99 (br d,y= 15.6 Hz, IH), 7.29 (td, J= 2.7,6.9 Hz, IH), 7.41 (d,./= 7.8 Hz, IH), 7.45-7.58 (m, 3H), 7.64 (d, J = 15.6 Hz, 1H), 8.43 (s, IH). MS (ESI*) (M+H)* at m/z 455. Anal. Calcd for C24H26N2O5S • 0.08 H2O: C, 63.22; H, 5.78; N, 6.14. Found: C, 63.21; H, 5.65; N, 6.00. Example 244 f2-Isopropvlphenvl')[2-nitro-4-f £-((4-carboethoxvpiperidin-1 -vncarbonvltethenvP phenyl! sulfide The title compound was prepared by the procedures described in Example 225, substituting ethyl nipecotatc with ethyl isonipecotate, to give a light-yellow solid. 'II NMR(CDC13, 300MHz)8 1.18 (d, .7=6.9 Hz, 6H), 1.27 (t,7= 7.5 Hz, 3H), 1.64-1.86 (m, 2H), 1.94-2.09 (m, 2H), 2.90-3.15 (m, III), 3.15-3.39 (m, IH), 3.44 (septet, J = 6.9 Hz, IH), 3.95-4.14 (m, IH), 4.16 (q, J = 7.5 Hz, 2H), 4.40-4.63 (m, 1H), 6.69 (d, J= 8.7 Hz, IH), 6.98 (d, J= 15.6 Hz, IH), 7.29 (td,./= 2.7,6.9 Hz, IH), 7.41 (d, J = 8.4 Hz, IH), 7.46-7.60 (m, 3H), 7.58 (d,J= 15.6 Hz, IH), 8.43 (s, IH). MS (ESI") (M+H)+atw/z483. Example 245 (2-Isopropvlphenvnf2-nitro-4-f £-((4-carboxvrjiperidin-1 -vl)carbonvl)ethenvl) phenvll sulfide The title compound was prepared by the procedures described in Example 226, substituting the ethyl ester from Example 225 with the ethyl ester from Example 244, producing a light-yellow solid. 'H NMR (CDC13, 300 MHz) 5 1.18 (d, J = 6.9 Hz, 6H), 1.65-1.89 (m, 2H), 1.97-2.14 (m, 2H), 2.59-2.74 (m, IH), 2.93-3.20 (m, IH), 3.20-3.42 (m, IH), 3.44 (septet, J= 6.9 Hz, IH), 3.97-4.18 (m, IH), 4.40-4.65 (m, IH), 6.70 (d, J - 8.7 Hz, IH), 6.97 (d, J= 15.6 Hz, IH), 7.30 (td, J = 2.7,6.9 Hz, IH), 7.41 (d, .7=8.7 Hz, IH), 7.46-7.65 (m, 3H), 7.60 (d,J= 15.6 Hz, IH), 8.43 (s, IH). MS (ESP) (M+H)+ at m/z 455. i Example 246 (2-IsopTOPvlphenvnr2-nitro-4-f ff-f((4-;>ioluenesulfonvlaminocarbonvl)piperidin-1 -vl)carbonvl)ethenvl) phenyl] sulfide The title compound was prepared by the procedures described in Example 229, 1 substituting the acid from Example 226 with the acid from Example 245. light-yellow solid; 'H NMR (d6-DMSO, 300 MHz) 5 1.14 (d, ./= 6.9 Hz, 6H), 1.18-1.39 (m, 2H), 1.67-1.79 (m, 2H), 2.39 (s, 3H), 2.60-2.75 (m, IH), 2.96-3.14 (m, IH), 3.26-3.42 (m, IH), 3.34 (septet, J= 6.9 Hz, IH), 4.10-4.42 (m, 2H), 6.62 (d, J= 8.4 Hz; IH), 7.32-7.43 (m, 4H), 7.45 (d, J = 15.6 Hz, IH), 7.58 (d, J= 8.4 Hz, 2H), 7.60 (d, J= 3.6 Hz, lH),7.78(d,J= 8.4 Hz, 2H), 7.87 (dd, J =2.7, 8.4 Hz, IH), 8.60(d, J=2.7Hz, III). MS (ESI) (M+H)~ at m/z 606. Anal. Calcd for C31H33N3O6S2 • 0.26 H2O: C, 60.80; H, 5.52; N, 6.86. Found: C, 60.85; H, 5.84; N, 6.61. Example 247 (2-Isopronvlphenvnr2-nitro-4-(g-((3-carboxv-4-hydroxvpiperidin-l- vDcarbonvPethenvl) phenyl! sulfide Prepared according to the procedures of Example 71, giving a yellow solid. 'H NMR (DMSO-dM 300MHz) 6 1.14 (d, J = 6.8 Hz, 6H); 1.53-1.70 (br m, 2H); 2.92-3.52 (br m, IH); 3.30-3.40 (m, IH); 3.98-4.44 (br m, 4H); 4.90-5.20 (br m, IH); 6.63 (d, J = 8.5 Hz, IH); 7.34-7.62 (m, 6H); 7.87-7.94 (br m, IH); 8.58-8.64 (br m, IH). MS (APCI) (M+H)4 at m/z 471. Anal calcd for C„HMN2S.O,: C, 61.26; H, 5.57; N, 5.95. Found: C, 61.05; H, 5.85; N, 5.73. Example 248 (Bcnzodioxan-6-vlH2-trifluoromethvl-4-(E-(Y3-carboethoxvpiperidin-l-vl) carbonvPethenvD phenyl! sulfide The title compound was prepared by the procedures described in Example 240 substituting N-(3'-aminopropyl)-2-pyTrolidinone with ethyl nipecotate, giving a white hygroscopic solid. 'H NMR (CDC1}, 300 MHz) 8 1.26 (t, J=7.0 Hz, 3H), 1.54 (m, IH), 1.65-1.80 (m, 2H), 2.10 (m, IH), 2.54 (m, III), 2.92-3.40 (m, 2H), 3.60-4.10 (m, 2H), 4.14 (q, J=7.0 Hz, 2H), 4.25-4.32 (m, 4H), 6.91 (d, J=7.5 Hz, IH), 7.00 (dd, J=2.0,15.0 Hz, 3H), 7.05 (d, J=2.0 Hz, IH), 7.40 (d, J=8.0, IH), 7.56 (d, J=15.0 Hz, IH), 7.76 (s, IH). MS (CI/NH3) m/z 522 (M+H)*. Anal, calcd. for C26 H^NC^S: C, 59.88; H, 5.02; N, 2.69. Found: C; 59.92; H, 5.39; N, 2.56. Example 249 (Benzodioxan-6-vPr2-trifluoromethvl-4-( £-((2-carboethoxvpiperidin-l -vl) carbonvllethenvB phenyl! sulfide The title compound was prepared by the procedures described in Example 240 substituting N-(3'-aminopropyl)-2-pyrrolidinone with ethyl pipecolinate. 'H NMR (CDC1„ 300 MHz) 8 1.28 (t, J=7.0 Hz, 3H), 1.35-1.54 (m, 2H), 1.64-1.82 (m, 3H), 2.30 (m, IH), 3.40 (m, IH), 4.00 (m, IH), 4.22 (q, J=7.0 Hz, 2H), 4.26-4.34 (m, 4H), 5.48 (m, IH), 6.91 (d, J=8.5 Hz, IH), 6.98 (m, IH), 7.02 (dd, J=2.0, 8.0 Hz, 2H), 7.06 (d, J=2.0 Hz, IH), 7.41 (d, J=8.0Hz, IH), 7.57 (d, J=15.0 Hz, IH), 7.77 (s, IH). MS (CI/NH3) m/z 522 (M+H)*. Anal, calcd for C26II26F3NOsS: C; 59.88; H, 5.02; N, 2.69. Found: C, 60.25; H, 5.12; N, 2.55. Example 250 (Benzodioxan^-vDj 2-nitro-4-f £-((4-carboxvpiperidin-1 -vll carbonyPethenvl) phenyl! sulfide The title compound was prepared by the hydrolysis of compound 198 under basic condition (aq. NaOH/EtOH), and purified by reversed-phase HPLC. 'H NMR (DMSO-ct 300 MHz) 5 1.44 (m, 2H), 1.78 (m, 2H), 2.04 (m, 2H), 2.82 (m, IH), 4.02-4.20 (m, 2H), 4.4.20-4.35 (m, 4H), 6.90 (d, J=8.0 Hz,lH), 6.97 (d, J=8.0 Hz, IH), 7.05(dd, J-2.0, 8.0Hz, IH), 7.10(d, J=2.0 Hz, IH), 7.15 (br, IH), 7,44 (m IH), 7.60 (br, IH), 8.40 (s, IH). MS (ESI) m/z 469 (M-l)". Example 251 (Benzodioxan-6-vl)r2-trifluoromethvl-4-(£-((3-carboxvpvrrolidin-1 - vllcarbonvltethenvl) phenvll sulfide The title compound was prepared according to the procedures of Example 1. 'H NMR (CDClj, 300 MHz) 5 7.75 (s, IH), 7.60 (d, IH, J = 15.0 Hz) 7.40 (br, IH), 7.06 (d, IH, J = 2.2 Hz), 6.96-7.02 (m, 3H), 6.90 (d, IH, J = 8.5 Hz), 4.30 (m, 5H), 3.99 (br, 2H), 3.29 (br, 2H), 2.60 (br, 2H), 1.85 (br, 2H). MS (ESI) m/z -492. Example 252 (Benzodioxan-6-vnf2-trifluoromethvl-4-(£'-((,4-carboethoxvpiperidin-l-vl1 carbonvnethenvll phenyl! sulfide The title compound was prepared by the procedures described in Example 240 substituting N-(3'-aminopropyI)-2-pyrrolidinone with ethyl isonipecotate, giving a white sticky solid. 'H NMR (CDC13, 300 MHz) 8 1.26 (t, J=7.0 Hz, 3H), 1.68-1.80 (m, 211). 1.98-2.10 (, 2H), 2.54-2.70 (m, 211), 3.00-3.30 (br, 211), 4.15 (nr, 3H), 4.26-4.34 (m, 4H), 6.90 (d, J=8.0 Hz, 2H), 7.00 (dd, J=2.0, 8.0 Hz, 2H), 7.06 (d, J=2.0 Hz, IH), 7.41 (m, IH), 7.50 (br, IH), 7.75 (s, IH). MS (CI/NH3) m/z 522 (M+H)~. Anal. calcd.forCyHjjFjNOjS'O.lHjO: C, 58.20; H, 4.52; N, 2.83. Found: C, 58.14; H, 4.69; N, 2.76. Example 253 (Bertzodioxan-6-vnf2-trifluoromethvl-4-(£-((2-carbomethoxv-4-/er/- butoxvcarbonvlpiperazin-1-vl') carbonvnethenvl) phenyl! sulfide ine uue compouna was prepared by the procedures described in Example 240 substituting N-(3'-aminopropyl)-2-pyrrolidinone with l-Boc-3-carbomethoxypiperazine, giving a white solid, mp 85-87 °C. 'H NMR (CDC13,300 MHz) 5 1.46 (s, 9H), 2.90-3.00 (m, 2H), 3.08-3.20 (m, 2H), 3.76 (s, 3H), 3.90 (m, IH), 4.25-4.34 (m, 4H), 4.58-4.66 (m, 2H), 6.92 (d, J=8.0 Hz, IH), 6.98 (m, IH), 7.02 (dd, J=2.0, 8.0 Hz, 2H), 7.06 (d, J=2.0 Hz, IH), 7.40 (m, IH), 7.62 (br, IH), 7.76 (s, IH). MS (APCI) m/z 609 (M+H)*- Anal, calcd. for C2,H31F3NAS: C, 57.23; H, 5.13; N, 4.60. Found: C, 57.09; H, 5.25; N, 4.37. Example 254 ('Benzodioxan-6-vn|'2-trifluoromethvl-4-(£-((2-carbomethoxv-4-methoxvcarbonvlpiperazin-1-vl') carbonvDethenvD phenyl! sulfide The title compound was prepared by treating the compound of Example 255 with methyl chloroformate and pyridine in CHjCI, at room temperature, producing a white foam. 'H NMR (CDC13,300 MHz) 8 3.00 (m, IH), 3.18 (m, 1II), 3.60 (m, IH), 3.72 (s, 3H), 3.76 (s, 3H), 3.90 (m, IH), 4.10 (br, IH), 4.28-4.34 (m, 4H), 4.64 (m, IH), 5.32 (m, IH), 6.85 (d, J=15.5 Hz, IH), 6.92 (d, J= 8.0 Hz, IH), 6.98 (m, IH), 7.02 (dd, J=2.0,8.0 Hz, IH), 7.08 (d, J=2.0 Hz, IH), 7.40 (d, J=8.0 Hz, IH), 7.64 (d, J=15.0 Hz, IH), 7.77 (s, IH). MS (CI/NH3) m/z 567 (M+Hf. Anal, calcd. for C26H,5F3N20,S: C, 55.12; H, 4.45; N, 4.94. Found: C, 55.18; H, 4.70; N, 4.68. Example 255 (Benzodioxan-6-yl)r2-trifluoromethyl-4-( E-( (2-carbomethoxvpiperazin-l -vl> carbonvllethenvn phenyl! sulfide The title compound was prepared by deprotection of compound 253 with TFA in CHJC12, resulting in a light yellow solid, mp 70-72 °C. 'H NMR (CDC13, 300 MHz) 52.90 (m, IH), 3.05 (m, IH), 3.35 (m, IH), 3.68 (m, IH), 3.80(s, 3H), 4 00 (m, IH), 4.25-4.34 (m, 4H), 4,70 (br, IH), 5.46 (m, IH), 6.84 (d, J=15.5 Hz, IH), 6.90 (d, J=8.0 Hz, IH), 6.96-7.04 (m, 2H), 7.06 (m, IH), 7.40 (d, J=8.0 Hz, IH), 7.65 (d, J=l 5.5 Hz, IH), 7.77 (s, IH). MS (CI/NH3) m/z 509 (M+H)+. Anal, calcd. for C34HMF3NAS*1-55H,0: C, 53.74; H, 4.90; N, 5.22. Found: C, 54.04; H, 4.59; N, 4.82. Example 256 (2-Methvl-3-(carhoethoxvmethvl1indol-5-vn[2-trifluoromethvl-4-( E-((morpholin-1- vlkarbonvPethenvP phenvll sulfide Example 256A (4-Bromophenvni2-trifluoromethvl-4-(£-((morpholin-l-vncarbonvl') ethenyl) phenvll sulfide The bromide was prepared by the procedure described in Example 12, substituting 2-bromothiophenol with 4-bromothiophenol, and 3,4-dichlorobenzaldehyde with 4-fluoro-3-trifluoromethylbenzaldehyde. Example 2S6B (4-Hvdra2inophenvnr2-trifluoromethvl-4-(,g-(fmorpholin-l-vlkarbonvl1 ethenvl) phenyl] sulfide, benzophenone hydrazone To a stirred solution of above-described bromide (1.0 g, 2.12 mmol) in 10 mL of toluene with Pd(OAc)2 (9.5 mg, 0.04 mmol), BINAP (40 mg, 0.06 mmol), and benzophenone hydrazone (437 mg, 2.12 mmol) was added NaO/-Bu (285 mg, 2.97 mmol). The reaction mixture was bubbled with N2 for 2 min before it was heated at 80 °C for 4 h. The reaction mixture was then allowed to cool down to ambient temperature. Ether was then added and the mixture was filtered through celite, washed with diethyl ether. The filtrate was concentrate in vacuo and the residue was purified on a SiO, flash column chromatography eluting with 10-30% EtOAc/hexanes to give 170 mg (13%) of the title compound as light brown foamy solid. Example 256C C2-Methvl-3-(carboethoxvmethvl1indol-5-vl')r2-trifluoromethvl-4-r£,-((morpholin-l-vDcarbonvPethenvP phenyl] sulfide To a stirred solution of hydrazone (90 mg, 0.15 mmol) in 2 ml- of cthanol was added levunilic acid (24 mL, 23 mmol) andp-TsOH (146 mg, 0.75 mmol). The mixture was then refluxed for 2 days. After cooled down to ambient temperature, the reaction mixture was partitioned between EtOAc and sat. NaHC03. The organic layer was then washed with brine, dried over Na,S04, concentrated in vacuo. The residue was then purified on Gilson preparative HPLC as described in Example 38B to give 6.0 mg (7%) of the title compound, light-brown solid. 'H NMR (CDC1„ 300 MHz) 8 1.20 (t,J= 7.4 Hz, 3H), 2.46 (s, 3H), 3.55-3.83 (brm, 8H), 3.67 (s, 2H), 4.12 (q, J = 7.4 Hz, 2H), 6.79 (d, J = 15.3 Hz, IH), 6.84 (d, J= 8.4 Hz, IH), 7.23-7.31 (m, 2H), 7.34 (d,./= 8.4 Hz, IH), 7.60 (d, J= 15.3 HA IH), 7.76 (s, IH), 7.80 (s, IH), 8.04 (s, IH). MS (ESO (M+H)+ at m/z 533. Example 257 n-(2-Methoxvethvnindol-5-vl)r2-chloro-4-( E-((4-acetvlpiperazin-l- vDcarbonvPethenvl) phenyl! sulfide The title compound was prepared by the procedures described in Example 232, substituting /-butyl bromoacetate with bromoethylmethvl ether, white solid; 'H NMR (CDClj, 300 MHz) 8 2.14 (s, 2H), 3.35 (s, 3H), 3.46-3.56 (m, 2H), 3.56-3.80 (m, 6H), 3.75 (t,y= 5.6 Hz, 2H), 4.33 (t, J= 5.6 Hz, 2H), 6.54 (d,J= 3.3 Hz, IH), 6.61 (d, J = 8.7Hz, lH),6.75(d,J= 15.3Hz, lH),7.09(dd,7=2.1,11.7Hz, 1H),7.26 (overlapping d, IH), 7.36 (dd, J= 2.1,8.7 Hz, IH), 7.44 (d, ./= 8.7 Hz, IH). 7.51 (d, J = 2.1 Hz, IH), 7.56 (d, ./= 15.3 Hz, IH), 7.88 (d, J = 1.5 Hz, IH). MS (ESF) (M+H)* at m/z 498, 500. Example 258 (2-IsoproDvlphenvl)r2-nitro-4-( ff-fG-acetoxvmethvl^-hvdroxvpiperidin-1 - vlkarbonvllcthenvn phenyl] sulfide Prepared according to the procedures of Example 71, giving a yellow solid. 'H NMR (DMSO-d6,300MHz) 8 1.14 (d, J = 7.0 Hz, 6H); 1.51-1.90 (br m, 2H); 1.92-2.06 (m, 3H); 2.50-3.21 (br m, 2H); 3.30-3.40 (m, IH); 3.40-4.44 (br m, 5H); 4.88-4.97 ( br m, IH); 6.63 (d, J = 8.5 Hz, IH); 7.31-7.62 (m, 6H); 7.87-7.94 (br m, IH); 8.58-8.64 (br m, IH). MS (APCI) (M+H)* at m/z 499. Anal calcd for C,6H30N2S,O40.29H2O: C, 61.98; H, 6.12; N, 5.56. Found: C, 62.00; H, 6.35; N, 5.55. Example 259 (2-IsopropvlphenvI')[2-nitro-4-(£-((3-rdimethYlaminocarbonvl')-4-hvdroxvpiperidin- 1-vlkarbonvPethenvl) phenyl] sulfide Prepared according to the procedures of Example 71, giving a yellow solid. 'H NMR (DMSO-d,, 300MHz) 5 1.14 (d, J = 6.8 Hz, 6H); 1.54-1.75 (br m, 2H); 2.81, 2.82 (br s, br s, 3H); 3.00, 3.04 (br s, br s, 3H); 2.75-3.60 (br m, 3H); 3.30-3.40 (m, IH); 3.90-4.28 (br m, 2H); 4.95-5.28 ( br m, IH); 6.61-6.66 (m, IH); 7.34-7.62 (m, 6H); 7.87-7.94 (br m, IH); 8.58-8.63 (br m, IH). MS (ESI) (M+H)' at m/z 498. Anal calcd for CMH31NJS,O50.34H!O: C, 61.99; H, 6.34; N, 8.34. Found: C, 61.96; II, 6.37; N, 8.56. Example 260 (2-lsopropvlphenvl)f2-nitro-4-f E-(Y3-cvanomorpholin-l-vlkarbonvllethenvl) phenyl] sulfide i-reparea according to the procedures of Example 71, giving a yellow solid. 'H NMR (DMSO-d,, 300MHz) 8 1.14 (d, J = 6.8 Hz, 6H); 3.30-3.40 (m, IH); 3.30-4.16 (br m, 5H); 4.20-4.29 (br m, IH); 5.07 (t, J = 3.5 Hz, IH); 6.65(d, J = 8.8 Hz, IH); 7.32-7.44 (m, 2H); 7.54-7.62 (m, 4H); 7.91 (dd, J = 8.8,2.0 Hz, IH); 8.67 (d, J = 2.0Hz,lH). MS (APCI) (M+H)4 at m/z 438. Anal calcd for CaH^S.CvO^SQH,.: C, 64.11;H, 5.82; N, 9.15. Found: C, 63.99; H, 6.00; N, 9.12. Example 261 {2-IsopropvlphenvlH2-nitro-4-(£-((3-carboethoxvmorphoHn-l-vlkarbonvl)ethenvl'> phenyl! sulfide Prepared according to the procedures of Example 71, giving a yellow solid. 'H NMR (DMSO-d4, 300MHz) 8 1.14 (d, J = 7.0 Hz, 6H); 1.12-1.27 (m, 3H); 3.30-3.40 (m, IH); 3.15-4.33 (br m, 9H); 6.64 (d, J = 8.5 Hz, IH); 7.32-7.42 (m, 2H); 7.50-7.62 (m, 4H); 7.88-7.96 (br m, IH); 8.65 (br s, IH). MS (APCI) (M+H)* at m/z 485. Anal calcd for CHaNjS.O,: C, 61.97; H, 5.82; N, 5.78. Found: C, 61.83; H, 6.07; N, 5.74. Example 262 (2-Isopropvlphenvl)[2-nitro-4-(£-(r3-('tetrazol-5-vl)morpholin-l-vl)carbonvl)ethenvn phenvll sulfide The compound of Example 260 (160 mg, 0.336), sodium azide (56.6 mg, 0.872 mmol), n-BujSnCl and THF were mixed in a reaction tube, flushed with nitrogen and heated to reflux overnight. The mixture was then cooled to ambient temperature and IN HCl soln. was added. The mixture was extracted with ethyl acetate three times and the combined organics were dried over MgS04. The mixture was filtered through a short silica gel plug to give 96 mg (56% yield) of the desired material. 'H NMR (DMSO-d,, 300MHz) 8 1.14 (d, J = 6.8 Hz, 6H); 2.96-4.62 (br m, 7H); 4.77 (dd, J = 10.5,2.7 Hz, 1H); 6.58-6.67 (m, 1H); 7.32-7.62 (m, 6H); 7.92 (dd, J = 8.8, 2.0 Hz, 1H); 8.62-8.67 (br m, 1H). MS (APCI) (M+H)- at m/z 481. Anal calcd for CH^S.O, 1.2H20: C, 54.93; H, 5.31; N, 16.71. Found: C, 54.97; H, 5.12; N, 16.50. Example 263 (,Benzodioxan-6-vl)f2-trifluoromethvl-4-( E-((4-carboxvpir>eridin-l-vO carbonvlkthenvD phenyl I sulfide The title compound was prepared by hydrolysis of the compound of Example 252 under basic conditions (aq. NaOH/EtOH), giving a white solid, mp 88 °C (dec). 'H NMR (DMSO-d6,300 MHz) 8 1.40 (m, 2H), 1.98 (m, 2H), 2.95 (m, 1H), 3.15 (m, 1H), 3.45 (m, 1H), 4.20 (m, 2H), 4.35 (m, 4H), 7.00 (m, 4H), 7.20 (m, 2H), 7.90 (m, 1H), 8.20 (m, 1H), 12.30 (s, 1H). MS (APCI) m/z 494 (M+H)'. Anal, calcd. for CMHJBF,NOJS«0.1 H20: C, 58.20; H, 4.52; N, 2.83. Found: C, 58.14; H, 4.69; N, 2.76. Example 264 r fBenzodioxan-6-vnf2-trifluoromethvl-4-(' E-((2-carboxvpiperidin-l -vll carbonvDethenvl) phenyl! sulfide The title compound was prepared by hydrolysis of the compound of Example 249 under basic conditions (aq. NaOH/EtOH), resulting in a white solid, mp 90 °G (dec). 'H NMR (DMSO-d,, 300 MHz) 8 1.15-1.50 (m, 2H), 1.50-1.70 (m, 2H), 2.16 (m, IH), 2.56 (m, III), 3.15 (m'( IH), 4.30 (s, 4H), 4.32 (m, IH), 5.20 (m, IH), 7.02 (m, 4H), 7.30-7.52 (m, 2H), 7.84 (m, IH), 8.15 (s, IH). MS (APCI) m/z 494 (M+H)*. Anal, calcd. for C24H„FjNO3'0.3 H20: C, 57.78; H, 4.57; N, 2.81. Found: C, 57.87; H, 4.5 7; N, 2.76. Example 265 (Benzodioxan-6-vl')[2-trifluoromethvl-4-f £-((4-carbomethoxvpiperazin-l-vl) carbonvPethenvD nhenvll sulfide The title compound was prepared according to the procedures of Example 1. 'HNMR (CDClj, 300 MHz) 8 7.76 (s, IH), 7.62 (d, IH, J = 15.0 Hz), 7.40 (d, 111, J = 8.6 Hz) 7.06 (d, IH, J = 2.1 Hz), 6.98-7.04 (m, 2H), 6.91 (d, IH, J = 8.4 Hz), 6.84 (d, IH, J = 15.6 Hz), 4.31 (m, 4H), 4.18 (q, 2H, J = 7.1 Hz), 3.68 (br, 4H), 3. 54 (br s, 4H), 1.29 (t, 3H, J = 7.2 Hz). MS (ESI) m/z 523, 545,1045,1067. Example 266 fBenzodioxan-6-vl')r2-trifluoromethvl-4-(£-(f3-aza-6.9-diooxaspirof5.41decan-l-vllcarbonvllethenvn phenyl] sulfide The title compound was prepared according to the procedures of Example 1. 'H NMR (DMSO-dj, 300 MHz) 8 8.13 (s, 1H), 7.84 (d, IH, J = 9.0 Hz), 7.48 (d, IH, J = 15.4 Hz) 7.38 (d, IH, J = 15.4 Hz), 6.98-7.06 (m, 4H), 4.30 (m, 4H), 3.92 (s, 4H), 3.74 (br, 2H), 2.62 (br, 2H), 1.63 (br, 4H). MS (ESI) m/z 508,1015. Example 267 (Benzodioxan-6-vl)r2-trifluoro-4-(£-f(4-(benzimidazolon-l-vnpiperidin-l-vPcarbonvPethenvn phenyl] sulfide The title compound was prepared according to the procedures of Example 1. 'H NMR (CDClj, 300 MHz) 5 8.32 (s, IH), 7.79 (s, IH), 7.66 (d, IH, J = 15.4 Hz), 7.44 (d, IH, J = 8.5 Hz), 7.0-7.12 (m, 6H), 6.94 (d, IH, J = 9.9 Hz), 6.90(d, IH, J = 2.6 Hz), 4.98 (m, IH), 4.59 (m,lH), 4.20 (m, 5H), 3.31 (br, IH), 2.83 (br, IH), 2.40 (m, 2H), 1.98 (m, 2H). MS (ESI) m/z 582, 604,1163, 1185. Example 268 (Benzodioxan-6-vl')r2-trifluoromethvl-4-f£'-rf4-fmethvlaminocaTbonvnDiDeridin-l- vDcarbonvllethenvl) phenyl] sulfide The title compound was prepared according to the procedures of Example 1. 'H NMR (CDClj, 300 MHz) 5 7.75 (s, III), 7.67 (d, IH, J = 15.4 Hz) 7.40 (d, III, J = 8.1 Hz), 7.06 (d, IH, J = 2.4 Hz), 6.96-7.02 (m, 2H), 6.90 (d, IH, J = 8.2 Hz), 4.28 (m, 4H), 3.95 (br, 2H), 3.50 (m, 1H),2.82 (s, 3H), 2.40(m, IH), 2.15 (br, IH), 1.88 (br, IH), 1.73 (br, 211). MS (ESI) m/z 507,529,1035. Example 269 fBenzodioxan-6-vI)f2-trifluoromethvl-4-(ff-((3-carbomethoxv-4-methoxvcarbonvlpiperazin-1-vl) carbonvPethenvD phenyl! sulfide The title compound was prepared by the procedures described in Example 240 substituting N-(3'-aminopropy!)-2-pyrrolidinone with 2-carbomethoxy-l-methoxycarbonylpipcrazinc, producing a light yellow solid, mp 56 °C (dec). 'H NMR (CDC13, 300 MHz) 5 2.70-3.50 (br, 4H), 3.70 (s, 3H), 3.76 (d, J=9.0 Hz, 3H), 4.00(m, IH), 4.20 (m, 4H), 4.50-5.00 (br, 2H), 6.91 (d, J=8.5 Hz, IH), 6.92-7.02 (m, 2H), 7.07 (d, J=2.0 Hz, IH), 7.25 (m, IH), 7.40 (m, IH), 7.60 (m, IH), 7.72 (s, IH). MS (APCI) m/z 567 (M+H)\ Anal, calcd. for C26H,5F,N30,S: C, 55.12; H, 4.45; N, 4.94. Found: C, 55.33; H, 4.74; N, 4.76. Example 270 (2-Isopropvlphenvnf2-nitro-4-( £-((3-carboxvmorpholin-l-vncarbonvl'teth.envn phenyl! sulfide Prepared according to the procedures of Example 71, giving a yellow solid. 'H NMR(DMSO-dt, 300MHz) 8 1.14 (d, J = 6.8 Hz, 6H); 3.08-4.33 (br m, 7H); 3.30-3.40 (m, IH); 6.58-6.68 (m, IH); 7.32-7.66 (m, 6H); 7.87-7.94 (m, IH); 8.53-8.65 (m, IH). MS (APCI) (M+H)' at m/z 457. Anal calcd for C^H^S,04: C, 60.51; H, 5.30; N, 6.14. Found: C, 60.33; H, 5.54; N, 5.80. Example 271 (Benzodioxan-6-vDf2-trifluoromethvl-4-( £-((2-carboxv-4-methoxvcarhonvlpiperazin-1-vn carbonvllethenvl) phenvll sulfide The title compound was prepared by treating the compound of Example 255 with methyl chloroformate and pyridine in CH,C1, at room temperature, and followed by hydrolysis under basic conditions (aq. NaOH/EtOH), producing a white solid, mp 102°C (dec.). 'H NMR (DMSO-d6, 300 MHz) 5 2.85 (m, IH), 3.02 (m, IH), 3.20 (m, IH), 3.40 (m, IH), 3.62 (s, 3H), 3.88 (m, IH), 4.29 (s, 4H), 4.35 (m, IH), 5.15 (m, 1II), 6.90-7.10 (m, 3H), 7.30 (d, J=15.0 Hz, 1 H), 7.40 (d, J=15.0 Hz, IH), 7.54 (d, J=15.0Hz, IH), 7.82 (m, IH), 8.15 (m, IH). MS (ESI) m/z 553 (M+H)'."Anal. calcd. for C,sH,3F3Nj07S' 0.25 H,0: C, 53.91; H, 4.25; N, 5.03. Found: 53.91; H, 4.35; N, 5.05. Example 272 (Benzodioxan-6-vl)f2-trifluoromethvl-4-('£-((morpholin-l-vl)carbonvl)ethenvn phenvll sulfide The title compound was prepared according to the procedures of Example 1. 'H NMR(CDC1„ 300 MHz) 8 7.76 (s, IH), 7.62 (d, IH, J = 15.6 Hz), 7.40 (dd, IH, J = 1.8,8.2 Hz), 7.04 (d, IH, J = 2.1 Hz), 6.98-7.03 (m, 2H), 6.91 (d, IH, J = 8.1 Hz), 6.81 (d, 1H, J = 15.3 Hz), 4.30 (m, 4H), 3.65-3.74 (br m, 8H). MS (ESI) m/z 452,474, 925. Example 273 (Benzodioxan-6-vl)f2-trifluoromeftvl-4-(£-(f4-(pvrrolidin-l-vnpiperidin-l-vltcarbonvlkthenvll phenyl! sulfide The title compound was prepared according to the procedures of Example 1. 'H NMR (CDClj, 300 MHz) 8 7.75 (s, IH), 7.65 (d, IH, J = 15.3 Hz), 7.40 (dd, IH, J = 1.4, 8.3 Hz), 7.06 (d, IH, J = 2.4 Hz), 6.98-7.02 (m, 211), 6.90 (d, IH, J = 8.1 Hz), 6.85 (d, IH, J = 15.3 Hz), 4.68 (m,lH), 4.20 (m, 4H), 3.10 (m,lll), 3.14 (m,lH), 2.81 (s, 4H), 2.58 (br, IH), 2.02 (s, 4H), 1.88 (s, 4H), 1.64 (m.lH). MS (ESI) m/z 519, 1037. Example 274 (2-IsopropvlphenvDr2-rutro-4-(£-((3-aza-6.9-diooxaspirof5.41decan-l- vlkarbonvllethenvl) phenyl! sulfide The title compound was prepared according to the procedures of Example 1. 'HNMR (CDC13,300 MHz)5 8.44 (s, III), 7.50-7.62 (m, 411), 7.4l(d, IH, J = 8.0 Hz), 7.30 (m, IH), 6.96 (br d, IH, J = 15.6 Hz), 6.69 (d, IH, J = 9.4 Hz), 4.00(s, 4H), 3.75 (brm,4H),3.44(m, IH), 1.75 (brs,4H), 1.18(d,6H, J = 7.0Hz). MS(ESl)m/z 439, 937. Example 275 f2-IsoproPvlphenyl)[2-[iitp>-4-('£-«2-fdimethylaminomethvl)Diperidin-l- vllcarbonvDethenvH nhenvll sulfide The title compound was prepared according to the procedures of Example 1. 'H NMR (CDCIj, 300 MHz) o 8.40 (d, IH, J = 1.8 Hz), 7.50-7.58 (m,4H), 7.42 (d, IH, J = 8.1 Hz), 7.30 (dd, IH, J = 1.9,7.0 Hz), 7.00 (d, IH, J= 15.4 Hz), 6.68 Example 276 (2-Isopropvlphenvl)f2-nitro-4-f£-('(piperidin-l-vlamino)carbonvnethenyl) phenyl] sulfide The title compound was prepared according to the procedures of Example 1. 'H NMR (CDCI,, 300 MHz)5 8.44 (d, IH, J = 1.8 Hz), 7.66(d, IH, J = 16.2 Hz), 7.55 (d, IH, I = 7.4 Hz), 7.47-7.51 (m, 3H), 7.30 (m,2H), 6.72 (d, IH, J = 8.5 Hz), 6.37 (s, IH), 3.48 (m,2H),3.10 Example 277 fpenzodioxan-6-vl)[2-trif)uoromethvl4-f £-(f3-carboxv-4- methoxvcarbonvlpiperazin-1-vl) carbonvllethenvl) phenyl] sulfide The title compound was prepared by hydrolysis of the compound of Example 269 under basic conditions (aq. NaOH/EtOH). 'H NMR (DMSO-aV 300 MHz) 5 2.60-3.30 (m, 3H), 3.40-3.50 (m, 1H), 3.62 (d, J=12.0 Hz, 1H),3.80 (m, 1H), 4.25-4.35 (m, 4H), 4.55 (m, 1H), 7.00 (s, 2H), 7.00-7.06 {m, 1H), 7.25 (m,2H), 7.5 (m, i lH),7.8O(m,lH),8.10 Example 278 I f2-(Dimethvlaminocarbonvn-benzodioxan-6-vn[2-chloro-4-(g-(f4-acstvlpippr!i/in^l- vljcarbpnvnethenvl) phenyl] sulfide The title compound was prepared by the procedures described in Example 85, substituting 5-iodoindole with 2-jVIA'-dimethylcarboxamide-6-bromobenzcnedioxane and 3-MA,'-dimethylcarboxarnide-6-bromobenzenedioxane, giving a white solid. lH NMR (CDCtj, 300 MHz, mixture of regioisomers) 5 1.93 (s. 3H), 2.15 (s, 6H). 3.53 (br s, 2H), 3.59-3.90 (brm, 8H), 4.86-5.01 (m, 1H). 6.74-6.81 (m, 1H), 6.80 (d, J = 15.3 Hz, 1H), 6.93 (d,J= 8.7 Hz, 1H), 7.02 (d,CDCljl.8 Hz, 1H), 7.13 (dd,J= 1.8, 8.4 Hz, 1H), 7.16-7.25 (m, 1H), 7.54 (s, IH), 7.58 (d, J= 15.6 Hz, 1H). MS (ESI') (M+Na)* at m/z 552,554. i Example 279 (2-IsopropvlDhenvnf2-nitro-4-(E-ff3-(2-fmeihoxvmethvlltetrazol-5-vhpiperidin-l-vllcarbonvllethenvll phenvll sulfide The title compound was prepared by the procedures described in Example 225, substituting ethyl oipecotate with 3-/V-methoxymethy!tetrazo[y]piperidine, to give a light-yellow solid. 'H NMR (CDC1„ 300 MHz) 6 1.19 (d,./= 6.9 Hz, 6H), 1.62-1.80 (br m, 2H), 1.80-2.20 (br m, 2H), 2.20-2.39 (br m, 2H), 3.12-3.38 (br m. 2H), 3.46 (s, 3H), 4.11 (septet, J= 6.9 Hz, IH), 4.17-4,34 (br m, IH), 5.79 (s, 211), 6.70 (br s, IH), 7.05 {d, J= 15.3 Hz, IH), 7.31 (d, J= 7.8 Hz, IH), 7,35-7.68 (m, 5H), 8.42 (brs, IH). MS(ESI')(M+H)atm/z523. Example 280 (2-lsopropvlphenvlH2-nitro-4-('£'-ff3-(l-(methoxvmethyl'lieirazol-5-vlipiperidin-l-vDcarbonvnethenvl) phenyl] sulfide The title compound was prepared by the procedures described in Example 279 and separated from the same reaction mixture via Si02 flash column chromatography, to give a light-yellow solid. 'H NMR (CDCI,, 300 MHz) 6 1.19 (d, J = 6.9 Hz, 6H), 1.62-1.80 (br m, 2H), 1.80-2.20 (br m, 2H), 2.20-2.39 (br m, 2H), 3.12-3.38 (brm. 2H). 3.46 (s, 3H), 4.11 (septet, y=6.9 Hz, IH), 4.17-4.34 (brm, IH), 5.79 (s, 2H), 6.70 (brs, IH), 7.05 (d,.7=15.3 Hz, IH), 7.31 (d, J= 7.8 Hz, IH), 7.35-7.68 (m,5H), 8.42 (br s, IH). MS (ESI*) (M+HT at m/z 523. Example 281 f1-Methvlindol-5-vhr2-chloro-4-f £-ff3-(l-pvrrolidin-2-onvl>prQpv]amino) carbonvDethenvn phenyl] sulfide Example 281A Triisoprspylsilvlf 1 -methyl in do!-5-vll sulfide To a stirred solution of 5-bromo-Ar-methyl indole (300 mg, 1.43 mmol) in 5 mL of benzene in a sealed tube was charged with Pd(PPhj), (82 mg, 0.072 mmol), followed by KSTIPS (326 mg, 1.43 mmol). The mixture was flushed with N2, the tube was capped, and the reaction mixture refiuxed for 2 h. The reaction mixture was theri allowed to cool down, partitioned between Et,0 and water. The organic layer was washed with brine, dried over Na;S04, concentrated in vacuo. The residue was purified on a SiG, flash column chromatography eluting with 5% EtOAc/hexanes to give 400 mg (88 %) of the title compound as colorless oil. Example 23TB 3-Chlon>-4-(n-methvlindol-5-vhihio1benzaidehyde To a stirred solution of thiolsilyl ether (1.0 g, 3.13 mmol) in 5 mL of DMF with 3-chloro-4-flurobenzaldehyde (500 mg, 3.13 mmol) at ambient temperature was added CsF (5.7 mg, 0.38 mmol). The mixture was stirred over night before it was poured in water and extracted with Et,0 (2x25 mL). The combined organic layer was washed with water and brine, dried over Na,SO„ concentrated in vacuo. The residue was purified on a Si02 flash column chromatography eluting with 5-10 % EtOAc/hexanes to give 650 mg (71 %) of the title compound as white solid. Example 281C n-Methvlindol-5-vhf2-chlofo-4-f£-f(3-fl-pvrrolidin-2-onYnpropvlamino^ carbonvDethenvn phenyl"! sulfide The title compound was prepared by the procedures described in Example 92, substituting the benzoic acid with cinnamic acid prepared from the above-described aldehyde, and ammonium with 3-aminopropyl-l -pyrrolidin-2-one, to give a white solid. 'H NMR (CDC1„ 300 MHz) S 1.74 {br m, 2H), 2.07 (br m, 2H), 2.44 (brm, 2H), 3.32 (br m, 2H), 3.40(br m, 4H), 3.85 (s, 3H), 6.36 (d, J= 15.3 Hz, IH), 7.14 (d, J= 3.0 Hz, IH), 7.36 (dd, J= 1.5,9.0 Hz, IH), 7.41 (d, ./ = 9.0 Hz, IH), 7.50 (s, IH), 7.89 (d, J- 1.5 Hz, IH). MS (ESI") (M+H)* at m/z 468,470. Anal. Calcd for C25H26CIN3O2S • 1.37 H2O: C, 60.95; H, 5.88; N, 8.53. Found: C, 60.97; H, 5.98; N, 8.46. Example 282 f2-lsopropvlphenvl)f2-nitTO-4-(£-l'f3-ftetrazol-5-vhpiperidin-i-vncarbonvl>ethenvr) phenyl) sulfide The compound from Example 279 (75 mg, O.Hmmol) was dissolved in \ ml, of neat TFA and left at ambient temperature for overnight. The reagent was then removed in vacuo and the residue was evaporated twice with benzene. The crude product was purified using Gilson Preparative HPLC as described in Example 38B to give the title compound as a light-yellow solid (50 rag, 72 %); 'H NMR (CDClj, 300 MHz)S1.17(d,J=6.5Hz,6H), 1.25-1.39(m, IH), 1.69-1.81 (m, IH),2.09(brs, IH), 2.14-2.30(m, IH), 2.57-2.71 (m, !H), 3.35-3.66 (m, 3H), 3.90-4.03 (m, IH), 4.66-4.78 (in, IH), 6.73 (d, J= 8.7 Hz, IH), 6.86 (d, J= 15.3 Hz, IH), 7.32(dd, J= 2.1,6.9 Hz, IH), 7.42 (dd, J= 2.1,8.7Hz, IH), 7.47-7.57 (m. 3H), 7.76 (d,J= 15.3 Hz, 1H), 8.46 (d, ./= 2.1 Hz, 1H). MS (ESI*) (M+H)' at m/z479. Anal. Calcd for C24H26N003S • 0.28 H20: C, 59.61; H, 5.54; N, 17.38. Found: C, 59.71; H, 5.44; N, 16.99. Example 281 fl-Methvlindol-5-vH|2-chloro-4-f ^-((3-carboethoxvpiperidin-l-vl'lcarbonvllethen^J phenyl] sulfide The title compound was prepared by the procedures described in Example 28IC, substituting am inopropyl pyrrol id inone with ethyl nipecotate, giving a white solid. 'H NMR (CDCI3, 300 MHz) 5 1.26 (t, J = 7.5 Hz, 3H), 1.65-1.96 (m, 2H), 2.00-2.20 (m, IH), 2.04 (s, IH), 2.54 (br m, IH), 3.12-3.34 (m, IH), 3.85 (s, 3H), 3.92-4.07 (m, IH), 4.07-4.20 (m, IH), 4.15 (q,y= 7.5 Hz, 2H), 4.65-4.90 (m, IH), 6.53 (d,./= 3.0 Hz, IH), 6.57(d, J = 8.1 Hz, IH), 6.85 (d, J= 15.3 Hz, III), 7.08 (d, J= 8.7 Hz, III), 7.14 (d, 7=3.0Hz, IH), 7.37 (dd, J= 1.5,8.7 Hz, IH), 7.42 (d. J= 8.7 Hz, IH), 7.51 (s, IH), 7.51 (d,y= 15.3 Hz, IH), 7.89 (d, J= 1.5 llz, HI). MS (ESI*) (M+H)' at m/2 483,485. Example 284 (1-Methylindol-5-Yl'l(2-chlorci-4-f £-((3-carboxvpiperidin-l-vl)carbonvl>ethenvl1 pheitvi] sulfide The title compound was prepared by the procedures described in Example 155, jbstituting the ethyl ester from Example 137 with ethyl ester from Example 283, and :OH with NaOH, to provide a white solid. 'H NMR (CDCI„ 300 MHz) 5 1.45-1.69 n, IH), 1.69-1.98 (m, 2H), 1.98-2.22 (m, IH),2.51-2.70 (m, IH), 3.05-3.47 (m. IH), .80-4.20 (m, 2H), 3.85 (s, 311), 4.47-4.68 Example 285 l-Methvlindol-5-vnf2-chloro-4-f £-(i,4-carboeth,9xypiperidin-l-vncarhonvl)ethenvl) phenyl] sulfide The title compound was prepared by the procedures described in Example B1C, substituting aminopropyl pyrrolidinone with ethyl isoiupceotate, giving a white )lid. 'H NMR (CDClj, 300 MHz) d 1.26 (t, J= 7.5 Hz, 3H), 1.64-1.83 (m, 2H), 1.88-.08 (m, 2H),2.48-2.67 (m, IH), 2.86-3.40 (m, 2H), 3.85 (s, 3H), 3.89-4.24 (m, IH), .15 (q,./ = 7.5 Hz,2H), 4.24-4.65 (m, IH), 6.53 (d,J= 3.0 Hz, IH), 6.58 (d,J= 8.1 z, IH), 6.81 (d,J= 15.3 Hz, IH), 7.07 (d,J= 8.1 Hz, IH), 7.14(4^=3.0 Hz, IH), 7.37 (dd, J= 1.5, 9.0 Hz, IH), 7.50 (d, .7=9.0 Hz, IH), 7.50 (d, J= 15.3 Hz, IH), 7.88 (d,y= 1.5 Hz. IH). MS (ESDtM+II)' atm/z483,485. Example 286 fl-Methvlindo]-5-vl)r2-chlQro-4-(E-(('3-carboxvpiperidin-l-vncaTbonvl)ethenvl) phenvll sulfide The title compound was prepared by the procedures described in Example 155, substituting the ethyl ester from Example 137 with ethyl ester from Example 285, and KOH with NaOH, giving a white solid. 'H NMR (CDC1,. 300 MHz) 5 1.60-1.90 (m, 2H), 1.90-2,10 (m, 2H), 2.57-2.72 (m, IH), 2,80-3.40 (m, 2H), 3.85 (s. 3H). 3.91-4.20 (m, IH), 4.30-4.68 (m, IH), 6.53 (d,J = 3.0 Hz, IH), 6.57 (d, 7 = 8.1 Hz, 1H), 6.80 (d, 7=15.3 Hz, IH), 7.07 (d, J-8.1 Hz, IH), 7.15 (d,7=3.0 Hz, IH), 7.37 (dd, J= ].5, 9.0Hz, IH), 7.51 (d,J=9.0Hz,lH), 7.51 (s, IH), 7.51 (d, J= 15.3 Hz,-IH). 7.89 (br s, IH). MS (ESP) (M+H)* at m/z 455, 457. Anal. Calcd for C24H23CIN2O3S ■ 0.42 H20: C, 62.32; H, 5.20; N, 6.06. Found: C, 62.35; H, 5.30; N, 5.87. Example 287 (2-IsopropvlphenvD[2-nitro-4-fg-f{ 2-f 1 -methvlpvrroIidin-2-yl)cthvlammo1carbonvl)ethenyl) phenyl! sulfide The title compound was prepared according to the procedures of Example 1. 'H NMR (CDClj, 300 MHz) & 8.44 (d, IH, J = 1.8 Hz), 7.56 (d, IH, J = 3.7 Hz). 7.50-7.58 (m, 3H), 7.43 (DD, IH, J = 1.84, 8.4 Hz), 7.30 (dd, IH, J = 2.2,6.8 Hz), 6.78 (d, IH, J = 8.5 Hz), 6.52 (d, IH, J = 15.8 Hz), 3,63 (m,2H), 3.42(m, 3H), 3.00 (m,lH), 3.78 (m.lH), 2.59 (s, 3H), 2.05 (m,lH),2.00 (m, 5H), 1.18 (d, 6H, J = 7.0 Hz). MS (ESI) m/2 454,490. Example 288 f2-Isopropvltihenvl'H2-nitTO-4-f£- phenyl] sulfide The title compound was prepared according to the procedures of Example 1. 'H NMR (CDCtj, 300 MHz) 5 8.43 (d; IH, J = 1.8 Hz), 7.57 (d, 1H, J = 8.5 Hz), 7.51-7.55 (m, 3H), 7.41 (dd, IH, J = 1.84, 8.8 Hz),7.31 (dd, IH, J = 2.4, 7.5 Hz),6.92 (d, IH, J = 15.4 Hz), 6.70 (d, IH, J = 8.5 Hz), 4.70 (m. IH), 4.10 (m,lH), 3.44 (pent, 1H, J = 6.8 Hz), 3.16 (m, IH). 2.80 (br, 411), 2.55 (br, IH), 2.03 (m,4H), 1.90(m,4H), l.65(m, IH), 1.18(d,6H,J = 7.0Hz).MS(ESl)m/i480,959. Example 289 [2-Isopropv]phenvnf2-nitro-4-(£'-('carbQnvl1cihenvl) phenyl] sulfide The title compound was prepared according to the procedures of Example t. 'H NMR (DMSO-d,, 300 MHz)5 8.63 (d, 3H, J = 1.8 Hz), 7.92 (dd, IH, J = 1.8,8.8 Hz), 7.60 (m, 3H), 7.47 (d, IH, J = 14.2 Hz), 7.42(d, IH, J = 14.2 Hz), 6.62 (d, IH, J = 8.5 Hz), 4.45 (m, 2H), 4.38 (m, 2H), 3.34 (m, 1H), 3.00 (m, 2H), 2.70 (m, IH), 2.60 (m,2H), 1.14 (d, 6H, J - 6.9 Hz). MS (ESI) m/z 491,981. Example 290 (2-IsQprQpyiphenvn[2-nitra-4-fg-(f3-hvdroxvpiperidin-l-vncarbonvI1ethenvh phenyl] sulfide The tide compound was prepared according to the procedures of Example 1. MINMR(CDCI,, 300 MHz) S 8.43 (s,lH), 7.50-7.62(m,4H), 7.41 Examnle 291 fBen?odinxan-6-Yn[2-trifluoromethvl-4-(£-ff3-(fethanesulfonvlaminokarponvnpiperidin-l-vl) carbonvlleihenvh phenyl} sulfide The title compound was prepared by the procedures described in Example 227. The product was purified by reversed-phase HPLC. 'H NMR (CDCI3,300 MHz) S \ .34 (t, J= 7.0 Hz, 2H), 1.44 (t, J=7.0 Hz, 3H), 1.95 (br, 1/2H). 2.20 (br, 1/2H), 2.68 (br, IH), 3.14 (q, J=7.0 Hz, 2H), 3.45 (m, IH), 3.65 (m, IH), 3.93 (m, 1H),4.30 (m, 4H), 4.50-4.60 (br, 2H), 6.92 (d, J=8.0 Hz, IH), 6.98-7.04 (m, 3H), 7.06 (m, IH), 7.40 (d, J=8.0 Hz, IH), 7.65 (m, IH), 7.75 (s, IH). MS (APCI) m/z585 (M+H) ■ Example 292 !Bq)ft^ioxan-b-vl)|2-tntluoromethYl-4-f f-»3-((p-toIuenesMtfonvlaminolcarbonvnpiperidin-1 -vl) carbonvltethenvU phenyl] sulfide The title compound was prepared by the same procedure described in Example 19, 'H NMR (CDC]„ 300 MHz) 5 1.25 (m,2H), 1.55 (m, IH), 1.70-2.25 (br, IH), 41 (d, J=13.0 Hz, 3H), 2.55 (br, IH), 3.50-3.80 (br, 2H), 4.20-4.35 (m, 4H), 4.68-75 (m, 2H),6.90 (d, J=8.0Hz, IH), 7.00-7.10 (m, 211), 7.30 (d, J=8.0 Hz, IH), 7.81 ,J=8.QHz,lH),7.91(m,lH). MS(CI/NH,)m/z647(M+H)'. Anal. cakd.for MHMFJNAS, *0-5 H20: C, 56.78; H, 4.61; N, 4.27. Found: C, 56.86; H, 4.69; N, 35. Exampie 293 (Benzodioxan-6-vlU2-trifluoromethyl-4-(£-f('4- ffeihanesulfonvlaroinokarbonvnpiperidin-l-vncarbonvltetbenvDDhenvH sulfide The title compound was prepared by the procedures described in Example 227, ving a while foam. 'H NMR (CDCl,, 300 MHz) 5 1.35-1.40 (m, 2H), 1.44 (t, J=7.0 z,3H), 1.76(m, IH),2.0(m, IH),2.50-3.20(br, IH),3.15(q, J=7.0Hz,2H),3.40-55 (m, 2H), 4.25-4.32 (m, 4H), 4.52 (br, 2H), 6.90 (d, J=8.0 Hz, 1H), 6.98-7.05 (dd, :2.Q, 8.0Hz,2H), 7,06 (d, J=2.0 HA IH), 7.40 (m. III), 7.60 (m, IH), 7.75 (s, IH), 22 (br, IH). MS (APCI) m/z 585 (M+H)\ Anal. cakd. for C26II,,FjN2O6S2'0.8 jO: C, 52.13; H, 4.81; N, 4.68. Found: C; 52.14; H, 4.80; N, 4.66. Example 294 (Benzodioxan-6-vl>f 2-trifluoromethvl-4-f g-((2(tetrazol-5-vnmorDho]in-1 -vhcarbonvDethenvll phepvll sulfide The corresponding nitrile (160 mg, 0.336 mmol, prepared via the procedures of Example 1), sodium azide (56.6 mg, 0.872 mmol), n-BujSnCl and THF were mixed in a reaction tube, flushed with nitrogen and heated to reflux overnight The mixture was then cooled to ambient temperature, and IN HCI soln. was added. The mixture was extracted with ethyl acetate three times and the combined organics were dried over MgSO,. The mixture was filtered through a short silica gel plug to give 96 mg (56% yield) of the desired material. 'H NMR (DMSO-d,, 500 MHz, I00°C)87.99 (d, 1H, J = 1.7 Hz), 7.79 (dd, 1H, J = 2-0, 8.6 H2), 7,50 (d, 1H, J = 15.3 Hz), 7.24 (d, JH, J = 15.6 Hz), 7.14 (d, 1H, J = 8.2 Hz). 6.96 (m, 1H), 6.94 (d, 1H, J = 2.1 Hz), 6.92 (m, 1H), 4.60 (dd, 1H, J = 3.0, 9.8 Hz), 4.50 (br d, 1H, J = 12.2 Hz), 4.26 (m, 5H),4.!7(m, IH),4.00(dt, 1H,J = 3.2, 11.6 Hz), 3.72 (td, 1H, } = 3.0,-11.0Hz), 3.43 (br m, IH), 3.29 (br m, 1H). MS (ESI) m/z -5! 8. Anal. Calcd for C23H20F3N5O4S ■ 1.83 HOAc: C, 50.88; H, 4.38; N, 11.13. Found: C, 50.61; H, 4.46; N, 11.4. Example 295 f2-lsopropvlphenvnf2-nitro-4-(£-(f2-butyl. 5-ftetrazol-5-vl>monjhotin-l- vncarbonvltethenvn phenvll sulfide Example 295A 2-Butvl-5-cvanomoTprioline The title compound was prepared by the procedures described in Example 260A, substituting ethanolamine with 2-aminohexanol. Example 295B f2-lsopropvlphenvnf2-niiro-4-('£-(('2-butvl-5-cvanomorpholin-l-vl1carbonvl>ethenvh phenyl] sulfide The title compound was prepared by the procedures described in Example 260B, substituting the morpholine from Example 260A with the compound of Example 295A. Example 295C (2-lsopropvlphenv1'if2-ttitro-4-(£-f(2-butvl-5-ftctrazol-5-v]1morpholiq-l-vncarbonvDethenvP phenyl! sulfide ITic title compound was prepared by the procedures described in Example 262, substituting the nitrile compound from Example 260 with the compound of Example 295B, giving a light-yellow solid. 'H NMR (CDCI„ 300 MHz, 3:2 mixtur: of diastereomers) 5 0.89 (!,./ = 7.5 Hz, IH), 1.01 (brm, IH), 1.19 (d,.7=6.5 Hz, 6H), 1.23-1.43 (m, 4H), 1.68-1.84 (m, IH), 3.10-3.61 (m, 2H), 3.83-4.17 (m, 2H),4.40-5.26 (m, 2H), 6.67-6.77 (m, IH), [6.91 (d), 7.02 (d), J= 15.3 Hz, IH in total], 7.25-7.37 (m, 2H), 7.44-7.60 (m, 3H), [7.67 (d), 7.79 (d), J= 15.3 Hz, IH in total], 8.43-8.50 (m, 1H). MS (ESI1) (M-H)' at m/z 535. Example 296 (2-fand 3-WHvdroxvmethvn-benzodioxan-6-vn(2-nitro-4- vllcarbonvl'tethenvl) phenyl) sulfide Example 296A Triisopropvlsilvl (2-fand 3-)hvdroxvmethvlbcnzodioxan-6-vl> sulfide The title compound was prepared by the procedures described in Example 281 A, substituting 5-bromo-Af-methy] indole with a mixture of 6-bromo-2-hydroxymethylbenzenedioxane and 6-bromo-3-hydroxymethytbcnzenedioxane. Example 296B f2-fand3-MHvdroxvmcihvlt-benzodioxan-6-vl)|2-nitro-4-f|g-(f4-acetvlpiperazin-l-vllcarbonvDethenvn phenvll sulfide The title compound was prepared by the procedures described in Example 281B, substituting 3-chloro-4-flurobenzaldehyde with 4-chlorc-3-nitrocinnarrude, giving a light yellow solid. 'H NMR (CDCIj, 300 MHz, 3:2 mixture of diastereomers) 8 [2.11 (s), 2.15 (s), 3H in total], 3.48-3.83 (m, 8H), 3.83-4.04 (m, 2H),4.20(dd,J= 8.4.11.4 Hz, IH),4.26-4.44 (m,2H), 6.89 {d,J= 5.7 Hz, IH),6.92 (s,lH),6.97-7.11 (m,lH), 7.04 (d,y= 15.0 Hz, lH),7.14(d,y=2.1 Hz, IH), 7.46 (br d, J= 9.0 Hz. IH), 7.65 (d, J= 15.0 Hz, IH), 8.41 (d, J= 2.1 Hz, 1H). MS (ESI*) (M+H)" at m/z 500. Example 297 (2- Example 298 (2-fand 3-yHvdroxvmethvlVr>enzodioxan-6-vD(2-trifluoromethv]-4-(E-f(3-(pvrrolidin-2-on-1 -vltprop-l -vl amino karbonvl) ethenvDphenvl]sulfide The title compound was prepared by the procedures described in Example 281, substituting 6-thiolsilyl indole with the thiolsilyl ether described in Example 296A, and 3-chloro-4-fluorobenzaldehyde with 4-iluoro-3-trifluoromethylbenzaldehyde, producing a white solid. *H NMR (CDC13,300 MHz, 3:2 mixture of diastereomers) 5 1.75 (br m, 2H), 2.09 (br m, 2H), 2.45 (br m, 2H), 3.25-3.60 (m, 6H), 3.804.43 (m, 5H), 6.46 (d,J= 15.3 Hz, IH), [6.92 (d),6.95 (d), J= 6.8 Hz, UI in total], (7.03 (d), 7.04(d), J= 8.1 Hz, 1H in total], 7.06-7.10 (ra, 1H), 7.13 (brs, 1H), 7.42 (d,J= 8.1 Hz, 1H), 7.54 (d, J= 15.3 Hz, 1H), 7.77 (s, 1H). MS (ESI*) (M+H)* at mil 537. Example 299 ('3-Hvdroxvmethvh-benzodioxan-6-vl1['2-nitro-4-tT£-ff3-fpvTTotidin-2-on-1-vnprop-l-v I aminotearbon v W ethen vl )phen v l]sul fide Example 299A 3 -f H vdrox vmethy l>-6- bromo-benzod ioxane To a stirred solution of 5-bromosalicyIaldehyde (5.0 g, 24.9 mmol). and epichlorohydrin (5.6 mL, 72.1 mmol) in 20 mL of DMF at 80 °C was added K2COs slowly in portions. The resulting mixture was then heated at 90 °C for 3 h. Reaction was then stopped, water was added, extracted with diethyl ether. The organic extracts were washed with water, brine, dried over Na3S04, concentrated in vacuo. The residue was purified on a Si03 flash column chromatography eluting with 15-30 % EtOAc/hexanes to give 2.82 g (44 %) of the title compound as colorless oil. To a stirred solution of the aldehyde (2.82 g, 11 mmol) in 35 mL of CHCI, was added mCPBA (2.27 g, 13 mmol). The mixture was stirred at ambient temperature for 30 min and then heated at 50 °C for 2 h. The reaction was then quenched with aq. NajSjOj, extracted with EtjO (2x50 mL). The combined organic layer was washed with aq. NaHCOj, brine, dried over Na^SOj, concentrated in vacuo to give 2.92 g of crude product which was proceeded to the next step without purification. To a stirred solution of the above-described crude formate (2.92 g) in 5 mL of THF was added 3Naq. NaOH (3.9 mL, 11.7mmoi). The reaction mixture was then heated at 70 °C for 4 h. The reaction mixture was then partitioned between EtOAc and water. The organic layer was then washed with brine, dried over Na2S04, concentrated in vacuo to give 2.50 g (93% over two steps) of the title compound. Example 299B Triisopropvl f3-(hvdroxvmethy|)-benzodioxan-6-Yl) sulfide The title compound was prepared by the procedures described in Example 281A, substituting 5-bromo-A'-methyt indole with the bromide from Example 299A, Example 299C (3-Hvdroxvmethvl>-benzodioxan-6-vnr2-niiro-4-(E-((3- 8.7 Hz, IH), 7.00 (d,J= 8.7 Hz, IH), 7.07 (dd,y=2.4,8.7 Hz, 1H),7,14 (d, J= 2.4 Hz, IH), 7.20(br s, IH), 7.46(dd, J= 0:9,8.7Hz, IH), 7.54 (d, J= 15.3 Hz, IH), 8.36 (s, 1H). MS (ESO (M+H)* al mlz 514. Anal. Calcd for C25H27N3O7S ■ 0.82 H20: C, 56.83; H, 5-46; N, 7.95. Found: C, 56.84; H, 5.18; N, 7.74. Example 300 fBenzodioxan-fi-vPf2-chloro-4-( E-fp-carboxvpiperidin-l-vOcarbonvPethenvn phenyl! sulfide The title compound was prepared by the procedures described in Example 263, substituting 4-fluoro-3-trifluoromethylbenzaldehyde with 3-chloro-4-fluorobenzaldehyde, giving a white solid. '11 NMR (CDCI,, 300 MHz) 5 1.64-1.88 (bi m,2H), 1.95-2.09(brm,2H),2.57-2.73 (m, IH),2.90-3.17(ro, IH),3.17-3.50(m, IH), 3.90-4.19 (m, IH), 4.25-1.36 (m,4H), 4.39-4.66 (m, IH), 6.75 (d,V = 8.4 Hz, IH), 6.84 (d,J= 15.3 Hz, IH), 6.93 {d, J= 8.7 Hz. IH). 7.03 (dd, J= 2.4, 8.7 Hz, IH), 7.08 (d, J= 2.4Hz, IH), 7.18 (d, J= 8.4 Hz, IH), 7.51 (s, IH), 7.54 (d, J= 15.3 Hz, IH). MS (ESI*) (M+H)* at mfz 460,462. Example 301 0-(and3-¥AminftmethvlVbenzodioxan-6-vl)[2-trifIuoromethvl-4-fE- 2-on-1 -vl)prop-l -vlaminokarbonvl) ethenvDphenv 11 sulfide Example 301A ^-(andB-MMesvloxvtnethvil-benzQdioxan-fi-vhfZ-trifluoromethvl-^fE-ffS-(pvnolidm-2^n4-vltooo-l-vla?rono>^aTbonvl'iethenvni>t\&Tivl]sulfide To a stirred solution of alcohol from Example 298 (200 mg, 0.37 mmol)) in 2 nL of methylene chloride with EtjN (104 mL, 0.74 mmol)) was added nethanesulfonyl chloride (35 mL, 0.56 mmol) dropwise. The mixture was then stirred it ambient temperature for one hour. The reaction mixture was then poured into 3N ICl, exuacted with EtOAc (2x 10 mL). The combined organic layer was washed with ,q. NaHCO,, brine, dried over NajS04, concentrated in vacuo to give 275 mg of crude ■roduct which was proceeded to the next step without purification. 2-fand3-yA2idomethvlVbenzodioxan-6-vli[2-trjfluoromethvl-4- bxampie-iOHJ Q-fandS-ifAminomethyD-benzodioxan-frvl^-tritluoromethvi^-fE-fG-fpyrrolidiri-2-on-l-vnprop-l-vlaminotearhonvl)cthenvhphenvl1sulfide To a stirred solution of azide (230 mg, 0.41 mmol) in 1 mL of THF was added PPhj {] 18 mg. 0.45 mmot), followed by one drop of water. The mixture was then stirred at room temperature for one hour. The volatile solvent was then removed in vacuo and ihe crude product was purified using Gilson Preparative HPLC as described in Example 38B to give 25 mg (11 %) of the title compound. Light brown oil; 'H NMR(CDCI3, 300 MHz, 3:2 mixture of diastereomers) 8 1.74 (brm, 2H), 1.96-2.16 (m, 2H), 2.35-2.50 (m, 2H), 3.23-3.47 C, 58.34; H, 5.48; N, 7.78. Example 302 f2-IsopfopvlphenvlH2-nitro-4-f g-dl-fmethvlaminocarbonvDmorpholin-1 - vl)carbonvl)ethenvl) phenyl] sulfide Prepared according to the procedures of Example 71, giving a yellow solid. 'H NMR (DMSO-d„ 300MHz) 6 1.14 (d, J = 6.6 Hz, 6H); 2.61 (d, J = 4.8 Hz, 3H); 3.14-4.62 (br m, 7H); 3.30-3.40 (m, 1H); 6.63 (d, J = 8.8 Hz, 1H); 7.32-7.62 (m, 6H); 7.80-7.97 (m, 211); 8.66(d, J = 1.5 Hz, 1H). MS (APCI) (M+H)' at m/z 470. Anal calcd for C1 Example 305 (Benzodioxan-6-vUt2-chloro^-(E-((3-(pviTOlidin-2-on-1 - vllprop-1- Example 309 for 1.5 hours. The mixture was cooled, and ice and HC1 were added. The resulting solid was filtered, washed with water and dissolved in tetrahydrofuran. This solution was dried over sodium sulfate, the solvent removed and ether added to give 1.733 g of product, m.p. 187-188C. 2H), 8.06{d, J—15 Hz, 1H). Ami. Calcd. for CijHyNOjS: C, 68.91; H, 6.57; N, 3.65. Found: C, 68.75; H, 6.67; N, 3.24. Example 314 Example 316 fBenzodioxan-fi-vnr2-chioro-4-f £-fr4-fmethviaminocarbonvi^piDerazin-l-vl1 (Bei]Zo4ioxan-6-vnf?-chloro-4-f £-ff4-fterrazol-5-vDpiDeridin-l-vhcarboirvltethenyll giving a white solid. 'H NMR (CDC1„ 300 MHz) 5 1.48-1.71 (m, 1H), 1.71-2.01 (m, fBenzodioxan-6-vlM2.3-dichloro-4-( £-((4-acetvlpiperazin-l-yhcarbonvl)ethenvl) phenyl] sulfide The title compound was prepared by the procedures described in Example 325, substituting aminopropyl pytrolidinone with I-acctylpiperazine. white solid; 'H NMR (CDC1„ 300 MHz) o 2.17 (s, 3H), 3.50-3.94 (m, 8H), 4.26-4.40 (m, 4H), 6.61 (d, J = 8.7 Hz, 1H),6.71 (d,./-15.6 Hz, 1H), 6.95 (d, 7=8.4 Hz, 1H), 7.04{dd,7=2.4,8.4 Hz, 1H), 7.09 (d,7 = 2.4 Hz, 1H), 7.30 (d,7= 8.7 Hz, 1H), 7.99 (d,7= 15.6Hz, 1H). MS (ESI*) (M+Na)+ al m/z 515, 517, 519. Anal. Calcd for C23H22CI2N2O4S ■ 0.52 CH2C12; C, 52.55; H, 4.32;N, 5.21. Found: C, 52.63; H, 4.16;N, 4.82. Example 330 Tlic title compound was prepared by the procedures described in Example 329, 5.04; N, 2.71. Found: C, 55.69; H, 4.90; N, 2.57. Example 337 n-MethvIindo]-5-vn[2.3-dich]oro-4-f £-(Y3-carboethoxvDiperidin-l-vh n-Methvlindol-5-vl)f213-dichloro-4-f £-(f4-caTboxvpiperidin-l-vncarbonvltethenvQ phenyl I sulfide The title compound was prepared by the procedures described in Example 155, substituting the ethyl ester from Example 137 with ediyl ester from Example 339, and KOH with NaOH, to give a white solid. 'H NMR (d*-DMSO, 300 MHz) S 1.31-1.53 (m, 2H), 1.62-1.76 (m, 2H), 1.94-2.09 (m, IH), 2.88 (brt, J= 10.5 Hz, 1H), 3.13 (brt, J= 10.5 Hz, IH), 3.86 (s, 3H), 3.93 (brd, J= 13.2 Hz, IH), 4.09 (br d, J= 13.2 Hz, lH),6.41 (d, J=> 8.7 Hz, IH),'6.53 (dd, .7=0.9, 3.0 Hz, IH), 7.04 (d,J- 15.3 Hz, lH),7.32(dd,J= 2.1,8.7Hz,lH),7.48(d,./=3.0Hz,IH),7.64(d,./= 8.7 Hz, ]H), 7.69 (d,J= 15.3 Hz, IH), 7.73 (d,J = 8.7 Hz, IH). 7.88 (d,J = 2.1 Hz, IH). MS (ESP) (M+H)' at m/z 489,491,493. Anal. Calcd for C24H2iCl2N2Na03S ■ 0 H20: C, 56.37; H, 4.14; N, 5.48. Found: C, 56.44; H, 4.38; N, 5.20. (66 g). The impure fraction from the mother liquor was flash chromatographed (8% Example 340F n-Methvlindol-S-vllfoS-dichloro-^ £-(Y4-carbometht3Xvpiperidin-l- 10.50 grams of the solid was suspended in methanol (60 mL), and was treated with a solution NaOH (0.859g) in methanol (20 mL). After all of the solid material went into solution, the solvent was removed under reduced pressure. The residua! yellow oil was triturated with ether, and dried to give the title compound as yellow powder(11.33g,95%). substituting 2-ethoxybenzenetbiol prepared according to the procedures of Example 97A, 'H-NMR(CDC1, 300 MHz) S 1.25 (t, J=7Hz, 3H), 3.55-3.80 (m, SH), 4.05 (q, J=7Hz, 2H), 6.63 (d, J=9Hz, 1H), 6.71 (d, J=15 Hz, 1H), 6.95-7.03 (m, 2H), 7.26 (d, J=9Hz,1H),7.39-7.50(rn,2H),7.99(d,J=15Hz,lH) Anal. Calcd. for Q.HJ^NOJS: C, 57.54; H, 4.82; N, 3.20. Found: C, 57.55; H, 4.77; N, 3.14. Example 344 O-tsoproDvlphenvhpj-diflMoro-^f^-fO-carboethoxvpiperidin-l- f2-Methoxvphenvl1[2-chlori>3-trifluorQmelhvl-4-('£-fl'4-carboethoxvpiperidin-l-vllcarbonvllethenvn phenvll sulfide Example 351A 3-Chloro-4-hvdroxv-2-(trifluoromethvDbenzaldehvde Chloroform (6.7g, 2.0 eq.) was added dropwisc to a stirred mixture of Ca(OH), (8.95g, I20mmol.), KjCO,(13.5g, 98 mmol.), 2-chloro-3-(trifluoromethyl)phenol (5.0g, 22 mmol.), and H,0 (50 mL) ai 60°-70° over 2 h. The reaction mixture was cooled, and acidified with cone. HC1. The product was extracted into EtOAc and dried over Na,SOj. Solvent was evaporated, the crude product was separated and purified through a silica column, eiuting with hexane and EtOAc (3:2) to give 580 mg (10%) of the title compound. Example 351B (2-Methoxvphenvl1[2-chloro-3-trifluoromethvl4-( f-carboxvethenvll phenvll sulfide The title compound was prepared according to the procedures described in Example 310, substituting the compound of Example 351A for 4-hydroxy-2,3-dichlorobenzaldehyde. Example 351C f2-Methoxvphenvl1f2-chloro-3-trifluornmethyl-4-( E-(f4-carboethoxvpiperidin-1 - yi)carbonvnethenvl> phenyl] sulfide To the acyl chloride (37 mg, 0.1 mmot) prepared from the compound of Example 35IB, as a solution in CH2C12 was added 1.2 eq.. of ethyl isouipecotate and 1.2 eq. of Hunig's base. The mixture was stirred at room temperature for 20 min., -90% of the solvent was removed in vacuo, and the resultant solution was loaded on a silica column to elute with hexane and EtOAc (3:2) to give 51mg (98%) of the title compound. 'H-NMR (CDCI3,300MHz) 8 1.25 (t, J=7.5Hz, 3H), 1.65-1.78 (m, 2H), 1.92-2.02 (br, 2H), 2.51-2.60 (m, 1H), 2.93-3.24 (br, 2H), 3.82 (s, 3H), 3.88-3.96 (mJH),4.15 (q,J«7.5Hz, 2H), 4.40-4.50 (br, 1H),6.48 (d, J=15Hz, 1H), 6.72 (d, J=9Hz, 1H), 7.02 (d, J=7.5Hz, 2H), 7.12 (d, J=9Hz, 1H), 7.49 (t, J=9Hz, 2H), 7.86 (qq, J=4.5Hz, 1H). MS (DCI/NH3) m/e 528 Example 353 i2-MethoxvphenvlM2-chloro-3-trifluoromemy]-4-{ g-f(morpholin-)-vltoaibonvHethenvlt phenvl] sulfide Prepared according to the procedures of Example 351, giving 50 nig (91%) of the title compound. 'H-NMR (CDC15,300MHz) 8 3.56-3.62 (br m, 2H), 3.67-3.77 (br m, 6H), 3,85 (s, 3H), 6-45 (d, J=15Hz, IH), 6.73 (d. J=9Hz, 1H), 7.03 (d, J=9Hz, 2H), 7.09 (t, J=9Hz, 1H), 7.52 (d, J=9Hz, 2H), 2.93 (qi). J=6Hz, 1H). MS (DCI/NH,) m/z 458 (M+H)*. J-8.2Hz, 1H), 7.78 (d, J=15.6Hz, 1H), 7.80 (d, J=7.8Hz, IH). MS (ESI") m/z 545 {M- The title compound was prepared ftom the cinnamide acid of Example 331, using the procedures described in Example 340 and substituting methyl isonipecotate withN-[2-(2-hydroxyethoxy)ethyl]piperazine. ^H NMR (300 MHz, DMSO-dfi) 6 1.18 (d, 611), 3.0 (m, 3H), 3.30 (m, 2H), 3.50 (m, 10H), 3.80 (rtu 2H), 4.50 (t, 1H), 6.45 (d, 1H), 7.30 (d, 1H), 7.35 (dd, 1H), 7.55 (d, 1H), 7.60 (m, 2H), 7.75 (d, 1H), 7,80(d,lH). MS (ESF) m/z 523 (M+H)+. Example 359 fBenzodioxan-6vlU2.3-bi!i(tjifluoromethv]V4-i'E-(f4-carboxvpiperidin-l- vlkarbortvriethenvnphenypsulfide Example 359A ]-Meihvl-2.3-bjs(p-ifluororoethylV7-oxabicvelof2.2.1)hepta-2.5-diene Hexafluoro-2-butyne {21.0 g, 0.13 mol) was transferred into a reaction bottle and added 2-methylfuran (12.86 g, 0.157 mol). This resulting mixture bottle was sealed and heated for 15hr. at 120 °C. After cooling, the excess 2-methylfuran was rotoevaporated in vacuo at rt, to give crude title product (29 g, 92%), which was used directly. Example 359B 4-Methvl-2.3-bis(trifhioromethvnphenol A mixture of Example 359A (12.0 g, 0.05 mol) and boron trfluoride-diethyl ether complex (150 ml) was stirred at room temp overnight, then neutralized carefully with 20% aqueous potassium carbonate, then the mixture was extracted with ether. The ether layer was dried over MgSOj and evaporated under reduced pressure to afford \0.4g (85%) of the title compound. Example 359C 4-[4-Broniobenzenesufonvloxv-2.3-bisi'trifluoromethvl)|benzvlbromide The phenol compound ofExample359B (10 g, 0.04 mol) was treated with 4-bromobenzenesulfonyl chloride (11.0 g, 0.043 mol) and Huni&'s base (5.56 g, 0.043 mol) in CHiCij (150 ml). The solution was washed with water, brine and dried over MgS04. After evaporating the solvent, N-bromosuccinimide (7.3 g, 0.04 mol) and benzoyl peroxide (200 mg) were added and the mixture was suspended iifCCIj (100ml). The resulting mixture was refluxed for 13 hr. When the reaction was cooled, the white solid was filtered and washed with CClj to afford the crude title compound. This crude product was used for next step without further purification. Example 3S9D 4-Hvdroxv-2.3-bisftrfluoromeihvl)ben7.aldehvde The crude product of Example 3 59C was dissolved in 60 ml of DMSO and 20 ml of CH,CI2, and 12 g of trimethylaminc N-oxide added. The resulting mixture was stirred at rt for 2.5 hr. The reaction mixture was poured into an ice cold 50% saturated aqueous NaCI solution (200 ml) and extracted with ether (3X100 ml). The combined organic layer was washed with brine and dried over Na,SO,. After evaporation of solvent, the product was purified by column chromatography, eluted with hexane.EtOAc (3:2) to provide 3.0 g of the tiilc compound, plus 4.0 g of recovered 4-[4-bromobenzenesulfonyloxy-2,3-t>is(triluoromethyl)]toluenc. Example 359E (ff enzodi oxan-6-vh-[2.3-bis f trfluorom ethvl )-4- f E-carboethen v llphen vt Isul fide The title compound was prepared according to the procedures described in Example 330, substituting the compound of Example 359D for 4-hydrox-2,3-di chl orobenzaldehy de. Example 359F fBen2odioxan-6vlir2.3-bisftrifiuoromeihv]>-4-fE-(C4-carboxvpiperidin-l- vltearbnnvDethcnvPphenvllsuIfide The title compound was prepared from Example 359H by the procedures described in Example 330, giving a white solid. 'H NMR (CD3OD, 300MHz) S 1.65(br s, 2H),I.93-2.04 (m,2H), 2.57-2.65 (m, HI), 2.95-3.05 (m, 1H), 3.25 (m, 1H), 4.12 (m, IH), 4.28 (m.4H), 4.41 (m, 1H), 6.92-7.03 (m, 4H), 7.25 (d, J=9Hz, 1H), 7.72(d,J=9Hz, 1H),7.72-7.81 (m, 1H). MS(ESt) m/e 562 (M+H)*. Anal ededfor C^Hj.NO^S: C, 53.48; H, 3.77; N, 2.49. Found: C, 53.42; H, 3.69; N, 2.25. Found: C, 53.49; H, 4.88; N, 4.75. 28,N,4.65. Found: C,5I.48,H,4.12,N,4.45. 2.70 (t, 1H), 3.00 (m, 2H), 3.20 (m, 2H), 3.27 (m, 2H), 3.50 (m, 2H), 3.90 (s, 3H), 4.18 (br d, 1H), 4.40 (brd, 1H), 4.50 (t, 1H), 4.77 (d, 1H), 6.40 (d, 1H), 6.58 (d, 1H), 7.19 (d, 1H), 7.35 (d, IH), 7.5 0(d, 1H), 7.66 (d, 1H), 7.70(m, 2H), 7.80 ft. 1H), 7.88 (s, 1H). MS (ESI*) m/z 562 (M+H)+. Anal, calcd for C27H29Cl,N,SO4-0.25H2O: C, 57.19; H, 5.24; N, 7.41. Found: C, 57.07; H, 5.22; N, 7.13. The tiiie compound was prepared from Example 340F, by the procedures described in Example 340G, substituting methyl isonipecotate with piperadine-4-sulfonic acid. 'H NMR (300 MHz, DMSO-d6) 5 1.40 (m, 2H), 1.90 (m, 2H), 3.03 (m, m), 4.W(m, 3H), 4.42 (brd, 1H), 6.40 (d, J=OHz, 1H), 6.53 (d, J=3.1Hz, 1H), 7.15 (d, J=15.3Hz, 1H), 7.33 (dd, J=8.5, 1.7Hz, 1H), 7.48 (d, J=3.1Hz, 1H), 7.65 (d, J=8.5Hz, 1H), 7.67 (d, J=15.2Hz, 1H), 7.74 (d, J=8.8Hz, 1H), 7.87 (d, J=1.5Hz). MS (ESP) m/z 525 (M+H)+. Anal, calcd for C23H22N2CljS,O4-0-8 TFA: C, 47.91; H, 3.73;N,4.54. Found: C, 47.71; H, 3.84; N, 4.73. (2-Methoxvphenvh [2.3-dichloro-4-f.C-ff4-amino-4-carboxvpiDeridin-l- C, 52.80; H, 4.40; N, 5.05. Found: C, 52.74; H, 4.42; N, 5.11. Example 376C (2-MethoxvphenyD5-[8-(E-(f4-(aminocarhonv]'toiperidin-l-vl karbon vl lei hen vl Iquinol i n v Hsu I fide fBgnzodioxat\-6-v^p-trifluoiomgthvl-4-fE-{{2-cai:boxvpipe[idii>-l- t, 1H), 7.25 (d, 1H), 7.5-7.7 (m, 7H), 7.85 (d, 1H), 10.40 Incubation continues for i hour ai room temperature and the wells are washed twice where "background" refers to wells (hat are not coated with anti-LFA-1 antibody. f uM Calceiun AM (MolecularProbes), are incubated at 17*0 for 30 minutes and washed once with RPMI-1640/1 % fetal bovine serum. Dilutions of compounds lo be assayed for ICAM-I/LFA-1 antagonistic activity are prepared inRPMl-1640/1% fetal bovine serum from 1 OmM stock solutions in DMSO and 50 uL are added to duplicate wells. Microliter plates are incubated for 45 minutes at room temperature and the wells are washed gently once with RPMI-1640/ 1% fetal bovine serum. Fluorescent intensity is measured in a fluorescent plate reader with an excitation wavelength at 485 nM and an emission wavelength at 530 nM. The percent inhibition of a candidate compound at a given concentralion is calculated using the following equation: a rat adjuvant arthritis model according to the method of HalloTan, et al., Anhilis The ability of compounds of this invention to treat radiation pneumonitis can be demonstrated in a murine pulmonary irradiation model according to the method of Hallahan et a!., Proc Natl Acad Set USA 94:6432-6437,1997. The ability of compounds of this invention to treat reperfusion injury can be demonstrated in the isolated rat heart according to the method of Tamiya el ah, Immvnapharmacologv 29(1): 53-63. 1995, or in the anesthetized dog according to the tnodel of Ilartman et al., Cardiovasc Res 30(1): 47-54,1995. The ability of compounds of this invention to treat pulmonary reperfusion injury can be demonstrated in a ral lung allograft reperfusion injury model according to the method of DeMeester et al., Transplantation 6.2(10): 1477-1485,1996, or in a rabbit pulmonary edema model according to the method of Horgan et al.; Am J Phvi-iol26U5\. H1578-H1584, 1991. The ability of compounds of this invention to treat stroke can be demonstrated in a rabbit cerebral embolism stroke model according the method of Bowes et al., Exp Neurol 119(2): 215-219,1993, in a rat middle cerebral artery ischemia-repcrfusion model according to the method of Chopp et al.,Stroke 25(4): 869-875,1994. or in a rabbit reversible spinal cord ischemia model according to the method of Clark et al., Neurosun 75(4Y. 623-627,1991. The ability of compounds of this invention to treat peripheral artery occlusion can be demonstrated in a rat skeletal muscle ischemia / reperfusion model according to the method of Gute et al.. Mot Cell Biochem VJ2- 169-187,1998. The ability of compounds of this invention to treat graft rejection can be demonstrated in a murine cardiac allograft rejection model according to the method of Isobe et al., Science 255: 1125-1127,1992, in a murine thyroid gland kidney capsule model according to the method of Talento et al.. Transplantation 55:418-422,1993, in a cynomolgus monkey renal allograft model according to the method of Cosimi et 1, J Immunol 144: 4604-4612,1990, in a rat nerve allograft model according to the nethod of Nakao et al.. Muscle Nerve 1£: 93-102,1995, in a murine skin allograft node! according to the method of Gorczynski and Wojcik, J Immunol JJ2 : 2011-;019, 1994, in a murine corneal allograft model according to (he method of He et al., Ipihalmol VhSci3^: 3218-3225,1994, or in a xenogeneic pancreatic islet cell ransplantation model according to the method of Zeng et at., Transplantation 5_8:681->B9, 1994. The ability of compounds of this invention to treat graft-vs.-host disease [GVHD) can be demonstrated in a murine lethal GVHD model according to the method ofHaming et a!., Transplantation 52:842-845,1991. The ability of compounds of this invention to treat cancers can be demonstrated in a human lymphoma metastasis model (in mice) according to the niethodofAoudiitet at.. J Immunol 161:2333-2338.1998. WE CLAIM: 1. A cinnamide compound of formula I wherein R1( R2, R3, R4 and R5 are independently selected from a. hydrogen, b. halogen, c. alkyl, d. haloalkyl, e. alkoxy, f. cyano, g. nitro, h. carboxaldehyde, and with the proviso that at least one of R, to R3 is a "ci's-cinnamide" or a "(rans-cinnamide", defined as wherein Rfl and R9 are independently selected from a. hydrogen, b. alkyl. c. carboxy alkyl, d. alkylaminocarbonyl alkyl, and e. dialkylaminocarbonyl alkyl, and R10and Rn are independently selected from a. hydrogen, b. alkyl, c. cycloalkyl, d. alkoxycarbonylalkyl. e. hydroxyalkyl, f. heterocyclyl representing a 4-. 5-, 6- or 7-membered ring which contains one, two or three heteroatoms independently selected from nitrogen, oxygen and sulfur, which can be fused to one or two rings independently selected from an aryl ring as defined below, a cyclohexane ring, a cyclohexene ring, a cyclopentane ring, a cyclopentene ring or another monocyclic heterocyclic ring, g. heterocyclylalkyi, where the heterocyclyl is as defined above, h. heterocyclylamino, where the heterocyclyl is as defined above, i. a heterocyclyl group as defined in f. above having substituents independently selected from a Iky I, halogen, hydroxy and alkoxy; j. a heterocyclylalkyi group as defined in g. above having substituents independently selected from alkyl, hal¬ogen, hydroxy and alkyoxy; or where NR10R1t is a heterocyclyl or substituted heterocyclyl group where the heterocyclyl group is as defined in f. above and the substituents are independently selected from 1) alkyl, 2) alkoxy, 3) alkoxyalkyl, 4) cycloalkyl, 5) an aryl group being a mono- or bicyclic carbocyclic ring system having one or two aromatic rings which can be fused to a cyclohexane, cyclohexene, cyclopentane or cyclopentene ring, 6) a heterocyclyl group as defined above, 7) heterocyclylcarbonyl, where the heterocyclyl is as defined above, 8) heterocyclylalkylaminocarbonyl, where the heterocyclyl is as defined above, 9} hydroxy, 10) hydroxyalkyl, 11) hydroxyalkoxyalkyl. 12)carboxy, 13)carboxyalkyl, 14) carboxycarbonyl, 15)carboxaldehyde, 16)alkoxycarbonyl, 17) arylalkoxycarbonyl. where the aryl is as defined above. 18)aminoalkyl, 19)aminoalkanoyl, 20) carboxamido, 21) alkoxycarbonylalkyl, 22) carboxamidoalkyl, 23)cyano, 24)tetrazolyl, 25) substituted tetrazolyl. 26) alkanoyl, 27)hydroxyalkanoyl, 28) alkanoyloxy, 29) alkanoylamino, 30) alkanoyloxyalkyl, 31) alkanoylaminoalkyl, 32) sulfonate, 33)alky1sulfonyl. 34) alkysulfonylaminocarbonyl, 35) arylsutfonylaminocarbonyl. where the aryl is as defined above, and 36) heterocyclylsulfonylaminocarbonyl, where the heterocyclyl group is as defined above, and wherein Ar is a substituted aryl or substituted heteroaryl group, which has one or two aromatic rings and which can be fused to a cyclohexane, cyclohexene, cyclopentane or cyctopentene ring, where substitutions are inde¬pendently selected from a. hydrogen, b. halogen, c. alkyl, d. an aryl group as defined above, e. haloalkyl, f. hydroxy, g. alkoxy, h. alkoxyalkyl, i. alkoxycarbonyl, j. alkoxyalkoxy, k. hydroxyalkyl, I. aminoalkyl, m. aminocarbonyl, n. alkyl(alkoxycarbonylalkyl)aminoalkyl, o. a.heterocyclyl group as defined above, p. a heterocyclylalkyl group as defined above, q. a heterocyclylalkyl group as defined above having substituents independently selected from alkyl, halogen, hydroxy and alkoxy; r. carboxaldehyde, s. carboxaldehyde hydrazone, t. carboxamide, u. alkoxycarbonylalkyl, v, carboxy, w. carboxyalkyl, x. hydroxycarbonylaikyl(carboxyalkyl), y. hydroxyalkylaminocarbonyl, z.cyano, aa. amino, bb. heterocyclylalkylamino. where the heterocyclyl is as defined above, cc. heterocyclylaminocarbonyl, where the heterocyclyl is as defined above, and dd. "fra/is-cinnamide", provided that (i) if Ar is phenyl and R,, R2, R4, and R5 are simultaneously hydrogen, then R3 is not a c/'s-cinnamide or trans-cinnamide where Re is methyl, R$ is hydrogen and R10 and R1t are simultaneously -C2H5, and (ti) if Ar is pyridyl or C^_3 alkyl substituted pyridyl. and Rv R2, R4. and R5 are simultaneously hydrogen, then R3 is not a cis-cinnamide or frens-ctnnamide where RB is hydrogen, R9 is hydrogen or C,.3 alkyl. and R10 and Rn are independently hydrogen, CM alkyl, or C3^ cyctoalkyl, or a pharmaceutical^ acceptable salt thereof. 2. A cinnamide compound according to Claim 1 wherein R, is a "c/s-cinnamide" or a "frans-cinnamide". and R3 is hydrogen. 3. A cinnamide compound according to Claim 1 wherein R3 is a "c/s-cinnamide" or a "trans-cinnamide", and R, is hydrogen. 4. A cinnamide compound according to Claim 1 wherein R3 is a "c/s-cinnamide" or a "frans-cinnamide", andR^Rg, and R9 are hydrogen. 5. A cinnamide compound according to Claim 4 wherein R3 is a "c/s-cinnamide". 6. A cinnamide compound according to Claim 4 wherein R3 is a "frans-cinnamide". 7. A cinnamide compound according to Claim 1 wherein R3 is a "c/s-cinnamide" or a "(rans-cinnamide", R^Rj, and RA are each independently hydrogen or alkyl; and R5 is selected from halogen, haloalkyl, and nitro. 9. A cinnamide compound according to Claim 4 wherein Ar is aryl, substituted aryl, heteroaryl, or substituted heteroaryl. I. A cinnamide compound according to Claim 4 wherein R10 and R1( are each independently selected from hydrogen, alkyl. cycioalkyl, alkoxycarbonylalkyl, hydroxyalkyl, and heterocyclylalkyl. 0. A cinnamide compound according to Claim 4 wherein NR^R,, is heterocyclyl or substituted heterocyclyl. 1. A cinnamide compound according to Claim 8 wherein Aris selected from substituted phenyl, 1,3-benzimidazol-2-one, 1,4-benzodioxane, 1,3-benzodioxole, 1-benzopyr-2-en-4-one, indole, isatin, 1,3-quinazolin-4-one, and quinoline. 12. A cinnamide compound according to Claim 1 selected from : {2.4-Dichlorophenyl)[2-(£-{(6-hydroxyhexylamino)carbonyl)ethenyl)phenyllsulfide; (2,4-Dichlorophenyl)[2-(£-((3-(1-imidazolyl)propylamino)carbonyl)ethenyl)phenyl]sulfide; (2,4-Dichlorophenyl)f.2-chloro-4-(E-({2hydroxyethylamino)carbonyl)ethenyl)phenyl]sulfide; (2,4-Dichlorophenyl)[2-chloro-4-(£-({6ydroxyhexytamino)carbonyl)ethenyl)phenyl]sulfide; (2,4-Dichlorophenyl)[2-chloro-4-{E-({bis-(2-hyd roxyethyl)am ino)carbonyi)etheny I )phenyl]sulf ide; (2.4-Dichlorophenyl)[2-chloro-4-{E-({3-(1-pyrrolidin-2-only)propylamino)carbonyl)ethenyi)phenyl]sulfide; (2,4-Dichlorophenyl)[2-chloro-4-(E-((1-morpholinyl)carbonyl)ethenyl)phenyllsulfide; (2,4-Oich(orophenyl)[2-chloro-^- (2,4-Dichlorophenyl)[2-chloro-4-{E-((4-acetylpiperazin-1-yi)carbonyl)ethenyl)phenyl]sulfide; (2,4-Dichloropheny I )[2-ch loro-4-(E-((4-(2-py ridyl Jpiperazin-1 -yl)carbony l)ethenyl)phenyl]sulfide; (2-(Hydroxy methyl )phenyl)[2-chloro-4-(E-((1-morpholinyl)carbonyl)ethenyl)phenyl]sulfide; (2-Bromophenyl)(2-chioro-4-(E-((1-morpholinyl)carbonyl)ethenyl)phenylJsulfide; (2,4-Dichlorophenyl)[2-chloro-4-(£-((4-(2-hydroxyeihyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]suiride; {2,4-Dichlorophenyl)[2-chloro^-(E-((4-(2-hydroxyethoxyethyl)piperazin-1-yl)carbonyl)ethenyl)phenylJsulfide; (2-Bromophenyl)[2-chloro-4-(f-((3-(hydroxymethyl)piperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-BromophenylH2- (2-Bromophenyl)|2-chloro-4-(E-((3-acetamidopyrrolidin-1-yl)cartonyl)ethenyl)phenyl]sulfide; (2-Bromophenyt)[2-chloro-4-(£-((4-hydroxypiperidin-1-yl)carbonyl)ethenyt)phenyl]sulfide; (2-Bromophenyl)[2-chloro-4-{£-((plperidin-1-yl)carbonyl)ethenyl)pheny]]sulfide; (2,4-Dichlorophenyl)[2-chloro-4-(E-((3-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2.4-Dichlorophenyl)[2-chtoro-4-(E-«4-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyllsulfide; (2-Bromophenyi)[2-chloro-4-(E-((4-acetylhomopiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-Bromophenyl)[2-chtoro-4-(E-((thiomorphotin-1-yl)cart)onyl)ethenyl}phenyl]sul{ide; (2-Bromophenyl)(2-chloro^-(E-((4-{1-ben2imidazol-2-only)piperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-Bromophenyl)[2-chloro-4-(E-((2-etrahydroisoquinolinyi)carbony!)ethenyl)phenyl]sLilfide; (2-Methylphenyl)[2-trifluoromethyl-4-{E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)ph8nyl]sulfide; (2-Methylphenyl)[2-trifluoromethyi-4-(E-{{1-morpholinyl)C3rbonyl)e)henyl)phenyl] sulfide; (2-Methylphenyl)[2-trtfluoromethyl^E-((2-{1-morpholinyl)emylamJno)carbonyl)elhenyl)phenyl]sulfide; (2-Methylphenyl)[2-trinuoramethyl-4-(E-((4-phenylpiperazin-1-yl)carbonyl)ethenyl)phenyl] sulfide; (2-Methylphenyl)[2-trifluoromethyl-4-(E-((3-(1-pyrrolidin-2-onyl)propylamino) carbonyl)ethenyl)phenylj sulfide; (2-Methylphefiyl)[2-trifluoromethyl-4-(E-((cyclopropylanfiino)carbonyl)etheriyl)pheriyl]sulfide; (2,4-Dichlorophenyl)[2-nitro-4-(E-({4-acetylptperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2,4-Dichlorophenyl)[2-nitro-4-(E-((3-(1-pyrrolidin-2-only)propylamino)carbonyl)ethenyl)phenyl]sulfide; (2,3-DichloraphenylH2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl}eihenyl)phenyl]su!fide; (4-Bromophenyl)(2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)elhenyl)phenyl)sutfide; (4-Methylphenyl)[2-nitro-4-(E-{(4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2,4-Dichlorophenyl)[2-nitro-4-(E-((4-(/ert-butoxycarbonyl)piperazin-1-yl)carbonyl)ethenyl)phenylJsulfide; (2,4-Dichlorophenyl)[2-nitro^-(E-((4-{2-furoylcarbonyl)piperazin-1-yl)carbonyl)elhenyl)phenyl]sulfide; (2,4-Dichlorophenyl)[2-nitro^-(E-((4-(methanesulfonyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2.4-Dtchlorophenyl)[2-nitro^-(E-((4-(diethylaminoMrbonylmethyl)piperazin-1-yl)carbonyl)ethenyl)phenyl] sulfide; {2,4-Dichlorophenyl)[2-nilro^-(E-((4-{dielhylaminocarbonyl)piperaziri-1-yl}carbonyl)ethenyl)phenyl]sulfide; (2,4-Dichlorophenyl)[2-nitro-4-(E*{(4-(/er(-butoxycarbony I methyl )piperazin-1-yl)carbonyl)ethenyl)phenyl] sulfide; (2,4-Dichlorophenyl)[2-nitro^-{E-{(4-(carboxycarbonyl)piperazin-1-yl)carbonyl)ethenyl)phenylJsuifide; {2,4-Dichlorophenyl)[2-nitro^-(£-{(4-(cartoxymethyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; {2-Methylphenyl)[2-nitro-4-{E-{(4-acetylpiperazin-1-yl)carbonyl)ettienyl)phenyl] sulfide; {2-Chlorophenyl)(2-nitfD-4-{E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl] sulfide; (2-Aminophenyl)[2-nitro-4-{E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-Hydroxymethylphenyl)l2-nitro-4-(£-({4-acetylpipera;:in-1-yl)carbonyl)ethenyl)phenyI]sulfide; (2-Ethylphenyl)[2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; {2-/so-Propylphenyl)[2-nitro-4-{E-{(4-acety!piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-tert-Butylphenyl)I2-nitro-4-(£-((4-acetylpiperazin-1-yl)carbonyl)etiienyl)phenyl]sulfide; (2-Chlorophenyl)I2-chloro-4-(E'-{(4-acetylpiperazin-1-yl)carbonyl))2-propenyl)phenyl]sulfide; (2-(1-^lo^pholinylmethyl)phe^yl)[2-chlo^o-4-{E-((1-morpholinyi)ca^bo^yl)ethe^yl)phe^yl]sulfide; (2-{4-0,3-Benzodioxolyl-5^ethyl)piperazin-1-ylmethyl)phenyl)[2-chloro-4-(£-((1-cnorpholinyl)carbonyl) ethenyl)phenyl]sulfide; (2-(4H'so-Propylaminocart>onylmethyl)piperazin-1-ylme^^ ethenyl)phenyl]sulfide; (2-((N-Ethoxycarbonylmethyl-«-methyl)aminomethy^^^ nyl)phenyl]sulfide; (2-Formy!phenyl)[2-chloro-4-(E-((1-morpholinyl)carbonyl)ethenyl)phenyl]sulfide; (2-(4-Fofrnylpiperazin-1-ytmethyOph8nyl)[2-chloro^-(E-((1-morpholinyl)carbonyl)ethenyl)phenyl]sulfide; (2-{£-{(1-Morpholinyl)carbonyl)ethenyl)phenyl)[2-chloro^-(£-((1-morpholinyl)cart)onyl)ethenyl)phenyl] sulfide: (2-Formylpheny1)[2-nitro-4-(£-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; {2-Formylphenyt)[2-chloro-4-{E-((1-morpholiny!)carbonyl)ethenyl)phenyl]su]ficle, N,N-dimethyl hydrazone; (2-((3-(1-Morpholinyl)propyl)-1-amino)phenyl)[2-chloro-4-(£-((1-morpholinyl)carbonyl)©thenyl)phenyl]sulfide; (2,4-Dichlorophenyl)[2-bromo-4-(£-({3-(1-pyrrolidin-2-only)propylamino)carbonyl)eihenyl)phenyl]sutfide; (2,4-Dichlorophenyi)[2-formyl-4-(£-({1-morpholinyt)carbonyl)elh6nyl)phenyl]sulfide: (2-Cyanophenyl)t2-chloro-4-(£-{(4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl] sulfide; (2-lsopropylphenyl)[2-cyano-4-(£-({morpholin-1-yl)carbonyl)ethenyl)phenyl]sijlfide; (2-Bromophenyl)[2-nitro-4-(E-((4-acetylpiperazin-1-yt)carbonyl)ethenyl)phenyl)sulfide; (2-(Pyrrolidin-1-yl)phenyl)I2-chloro-4-{E-((morpholin-1-yl)carbonyl)ethenyl)phenyllsulfide; (2-Melhoxyphenyl)-[2-ch!oro-4(E-[(morpholtn-1-yl)carbonyl]ethenyl)phenyl]sulfide; (2-lsopropylphenyl)[2-nitro-4-(E-({3-carbomettioxypiperazin-1-yl)carbonyl)ethenyl)phenyllsulfide; (2-Methylphenyl)[2-nitro^-(£-((3-cartJOxamido-4-cartobenzoxypipera2in-1-yl)carbonyl)ethenyl)phenyl] sulfide; (2-lsopropylphenyl)f2-nitro-4-(E-({2-carfcomethoxy^ phenyl]sulfide; (2-lsopropy1ph«iyl)[2-nilro^-(E-((2H;arboxy-4-terf-butoxycart)onylpiperaziri-1-yl)carbony'l)ethenyl)phenylJ sulfide; {2-lsopropylphenyl)[2-trifluoromethyl-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-isopropylphenyl){2-trifluoromethyl-4- (2-lsopropyJphenyl)[2Mrifluoromelhyl-4-{E-((3-(pyrrolidin-2-ori-1-yl)prop-1-ylamino)carbonyl)ethenyl)phenyl] sulfide; (2-lsopropylphenyl)[2-triftuoromethyl-4- (2-lsopropylpheny I )(2-f rifluoromethyt-4-{£-((cyclopenty la mtno)carbonyl)ethenyl )phenyl]sulf ids; (2-lsopropylphenyl)[2-trifluoromethyl-4-(E-((5-hydroxypent-1-ylamino)carbonyl)ethenyl)phenyl)sulfide; (2-lsopropy1phenyl)[2-r>itro-4-(E-((3-cartioniethoxy-4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-Biphenyl)[2-chloro-4-(E-((morpholin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (3,4-Dime^hy1phe^y,^J(2-rii^^-(£-((4-acefylpff3eTazin-^yl)(a^bo^yl)ethenyl)prteny(Jsu/f(de,■ (2-Bromophenyl)(2-trifluoromethyl-4-(£-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl}sulfide; (5-lndolyl)[2-chloro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfkle; {5-Benzodioxolyl)[2-chloro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)-t ethenyl)phenyl]sulfide; (2-lsoprc^)ylphenyl)(2-nitro-4-{E-((2-carbomethoxypiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2,3-Ditnelhoxyphenyl)-[2-chloro-4(£-[(morpholin-1-yl)carbonyl]ethenyl)phenyl)sulfide; (2-Fluorophenyl)[2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)eUienyl)phenyllsulfide; (2-Bromophenyl)[2-trifluorome1hyM-(£-((4-{(ert-butoxycarbonyl)piperazin-1-y1)carbonyl)ethenyl)phenyl] sulfide; (2-(Pyirolidin-1-yl)pheny1)[2-trifluoromethyl-4-(E- phenyl]sulfide; (3-Carboxafnidophenyt)f2-nttro-4-(£-((4-ace(ylpiperazin-1-yl)carbonyl)etfienyl^enyl] sulfide; (3-(Hydroxymethyl)phenyl)[2-nitro-4-{£-({4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; Phenyl[2-trifluoromethyl-4-(E-((4-(ferf-butoxycart>onyl)piperazin-1-yl)cafbonyl)ethenyl)phenyl]sulfide; (2Hsopropylphenyl)[2-trifiuoromethyl^-(£-({2-carbomethoxy-4-((erf-butoxycarbonyl)piperazin-1-yl)earbonyl) ethenyl )phenyl]sulfide; (2-lsopropylphenyl)l2-nitro^-(E-((3-(pyridine^-methylaminocarbonyl)-4-fert-butoxycarbonylpiperazin-1-yl) carbonyl Jethenyl )phenyl]sulf ide; 358 (2-Ethoxyphenyl)-[2-chloro-4(£-I(morptiolin-1-yl)cartx)nyl]ethenyl)phenyl]sulfide; (2-Melhoxyphenyl)[2-nitro-4-{E-{(4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl] sulfide; (2-(Azetidin-1-yl)phenyl)[2Mrifluoromemyl'4-(E-( nyljsulfide; (2-(Piperidin-1-yl)phenyl)[2-trifluorornethyl-4-{E-({4-((er(-butoxycarbonyl)piperazin-1-yt)carbonyl)ethenyl) phenyl]sulftde; (3-Chloro-2-formylphenyl)[2-chloro-4-(£-({4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-Trifluoromethylphenyl)[2-trifluoromethyl-4-(E-{(4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl)sulfide; (3-Bromophenyl)J2-trifluoromethyl-4-(£-((4-acetylpiperazin-l-yl)cart)onyl)etheny!)phenyt]sulfide; (3,5-Dimethylphenyl)[2-trifluoromethyl-4-(e-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyllsulfide; (2-lsopropylphenyl)[2-nitro-4-(E-{(3Hlimethytaminocarbonyl-4-(pyridine-4-carbony[)prperazin-1-yl)carbonyl) etheny l)phenyl] sulfide; (2-lsopropylphenyl)(2-nitro-4-(E-((3-dimethylaminocarbonyl-4-carbomethoxypiperazin-1-yl)carbonyl)efhenyl) ptienyl]sulfide; (2-lsopropylphenyl)[2-nifro-4-(E sulfide; (2-lsopropylphenyl)I2-nitro-4-(E-((3-(1-rtiorpholinocarbonyl)-4-(ert-butoxycait)onylpiperazin-1-yl)carbonyl) ethenyljphenyljsulfide; (2-lsopropylphenyl)[2-nitro-4-(E-((3-(pyridine-4-methylaminocartx>nyl)piperazin-1-yl)cart)onyl)ethenyl)phe- nyl]sulfide; (2-lsopropylphenyl)(2-nitro-4-(£-({(3-dimethylaminocarbonyl)piperazin-1-yl)earbonyl)ethenyl)phenyl]sulfide; (2-lsopropylphenyl)I2-nilro-4-(E-((3-{benzylaminoearbonyl)-4-(ert-butoxycarbonylpiperazin-1-yl)carbonyl) ethenyl)phenyl]sulfide; {2-lsopropylplienyl)[2-nitro-4-(E-({3-(dimethylaminocarbonyl)^-/ert-butoxycarbonylpiperazin-1-yl)carbonyl) ethenyl)phenyl]sulfide; (2-Bromopiienyl)[2^hloro^-(E-({3-(5S-hydroxymelhy(-pyrrolidin-2-on-1-yi)prop-1-ylarnino)carbony(}efhenyl) phenyi]sulfide; (2-Bromophenyl)[2-chloro-4-(E-((3-{pyrrolidin-2-on-1-yl)prop-1-ylamino)carbonyl)elhenyl)phenyl)sulfide; (2-Bromophenyl)(2-chloro-4-(E-(N-methyl-N-(3-(pyrrolidin-2KJn-1-yl)prop-1-yl)amino)carbonyl)ethenyl)phe- nyl]sulfide; (2-J2-Methoxy)ethoxyphenyl)-I2-chloro-4(E-[(morpholin-1-yl)carbonyl]ethenyl)phenylJsulfide; (2-lsopropylphenyi)[2-nitro^-(E-((3-(morpholinocarbonyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-lsopropylphenyl)(2-nitro-4-(E-{(4-/ert-butoxyGarbonyipiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; {2-lsopropylphenyl)|2-nitro-4-(E-((4-methoxycarbonylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-lsopropylphenyl)[2-nitro-4-(E-(4-(pyricJine-4-carbonyl)piperaziri-1-yl)carbonyl)ethenyl)phenyllsulfide; (2-lsopropylphenyl)[2-nitro^-(E-((3-(pyridine-3-melhylarninocarbonyl)-4-lerf-butoxycarbonylpiperazin-1-yl) carbonyl)elhenyt)phenyl|suffide; (2-lsopropylphenyl)(2-nitro^-(£- nyljsulfide; (2-lsopropylphenyl)[2-nitro-4-(E-((3-(pyridine-3-mefhylaminocarbonyl)piperazin-1-yl)carbonyl)ethenyl)phe- nyljsulfide; (4-Hydroxyphenyl)[2-nitro-4-{E-((4-acetyipiperazin-1-yl)carbonyl)elhenyl)phenyl]sulfide; (3,5-Dichlorophenyl)[2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyllsulfide; (2-Bromophenyl)[2-chloro^-{£-((3-(5S-acetoxymethyl-pyrrolidin-2-on-1-yl)prop-1-ylamino)carbonyl)ethenyl) phenyl}sulfide; (2-Bromophenyl)[2-chloro-4-(£-{(3-(5S-methoxymethyl-pyrrolidin-2-on-1-yl)prop-1-ylamino)carbonyl)ethe- nyl)phenyl]sulftde; (2-Bromophenyl)(2^hforo^-(E-(f3-(4ff-fiydroxyme(hy^pyrro(idin-2-on-1-yl)prop-1-ylamino)carbony()e(h phenyljsulfide, Phenyl(2-nitro-4-(E-((4-acelylpiperazin-1-yl)carbonyl)elhenyl)phenyl]sulfide; (2-Dimethylaminophenyl)[2-nitro-4-(£-((4-acetylpiperazin-1-yl)carbonyl)etheny!)phenyllsulfide; (3-((2-Hydroxyemyl)aminocarbonyl)phenyl)t2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl] sulfide; (3-((3-{1-lmidazolyl)propyl)aminocarbonyl)phenyl)l2-nitro-4-(£-((4-acetylpiperazin-1-yl)carbonyl)etbenyl) phenyl]sulfide; (3-{(2-(1-Morpholinyl)ethyl)aminocarbonyt)phenyl)(2-nitro^-(£-((4-acBtytpiperazin-1-yl)carbonyl)etfienyl) phenyl]sulfide; {2-lsopropylphenyl)[2-nitro-4-(E-((3-hydroxymethyl-4-tert-butoxycarbonylpiperazin-1-yl)carbonyl)ethenyl) phenyljsulfide; (2-Isopropylphenyl)[2-nitro-4-(E-((4-formylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-lsopropylphenyl)[2-nitro^-{£-((2-hydroxymethyM-ler(-butoxycarbonylpiperazin-1-yl)carbonyl)ethenyl) phenytjsuifide; (2-Ethoxyphenyl )-[2-chloro-4(E-[(3-ethoxycarbonylpiperidin-1 -yl )carbonyl]etheny l)phenyl]sulf ide; {3-Aminophenyl)(2-nitro-4-(E-{(4-acetylpiperazin-1-yl)carbonyl)ethenyl)ph8nyl]sulfide; {4-Amifiophenyl)[2-nitro-4-(£-{(4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2,4-Dimethylphenyl)[2-nitro-4-(£-{(4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyt]sulfide; (2,5-Dimethylphenyl)[2-nitro-4-(£-{(4-acetylpiperazin-1-yl)carbonyl)ethenyl)ph8nyl]sulfide; (4-Methoxyphenyl)[2-nitro-4-{E-((4-acetylpiperazin-1-yl)carbonyl)elfienyl)phenyl]sulfide; (3-Chtorophenyl)[2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]su]fide; (2-Chloro, 4.5-diaminophenyl)[2-ctiloro-4-{E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (3,4-Diaminophenyl)[2-chloro-4-{£-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl) (6-Chlorobenzimidazol-2-on-5-yt)[2-chloro-4-{E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)pfienylJsijlfide; (1-Methylindot-7-yl)[2-chloro-4-(E-({4-acetylpiperazin-1-yl)carbonyl)elhenyl)phenyllsulfide; (2-Hydroxy, 4-aminophenyl)[2-chloro-4-{E-((4-acetylpiperazin-l-yl)carbonyl)eihenyl)phenyl)sulfide; (2-lsopropylphenyl)[2-nilro-4-(E-((4-milhylpiperazin-1-yt)carbonyl)ethenyl)phenyl)sulfide; (2-lsopropytphenyl)[2-nitro-4-(E-((4-(pyridine-2-carbonyl)piperazin-1-yl)carbonyl)etheny1}phenyl]sulfide; (2-lsopropylphenyl)[2-nitro-4-(E-({4-(pyridine-3-carbonyl)piperazin-1-yl)carbonyl)6thenyl)ph8nylJsu|fide; (2-lsopropylphenyl)[2-nitro-4-(E-({2-carbomettioxy-4-methoxycarbonylpiperazin-1-yl)carbonyl)ethenyl)phe- nyljsulfide; (2-lsopropylphenyl)[2-nitro^-(E-((2-carboxy^-methoxycarbonylpiperazin-1-yl)carbonyl)ethenyl)phenyl] sulfide; (2-lsopropylphenyl)E2-nitro^-(E-((3-carbomethoxy-4-rnethylpiperazin-1-yl)cart)onyj)ethanyl)phGnyl)sulfide; (2-Ethoxyphenyt)-[2-chloro-4(E-[(3-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-Ethoxyphenyl)-[2-chloro-4(E-[(3-carboxypiperidin-1-yl)carbonyl]ethenyl)phenyl]sulfide; (2-Ethoxyphenyl )-[2-chloro-4(E-[(2-ettioxycarbonylpiperidin-1-y I )carbony l]elheny I )phenyllsulf ide; (2-Ethoxyphenyl)(2-trifluoromethyl-4-(E-{(1-(fert-butoxycarbonylH-nydroxypyrrolidin-3-ylamino)carbonyl) e (2-Elhoxyphenyl)-(2-chloro-4(E-[(2-carboxypiperidin-1-yl}carbonyl]ethenyl)phenyllsulfide; (2-Ethoxyphenyl)[2-trifluoromettiyl-4-{E-(((pyrrol-3-in-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-Ethoxyphenyl)[2-trifluoromelhyl-4-(E-((3-{pyrrolidin-2-on-1-yl)prop-1-ylamino)carbonyt)ethenyl)phenyll sulfide; {2-Ethoxypheriyl)[2-trifluorom6thyl-4-(E-({4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-Ethoxyphenyl)(2-trifluorornethyl-4-(E-({4-(ethoxycarbonyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-Ethoxyphenyl)(2-trifluoromethyM-(E-({4-{2-furylcarbonyl)pip9razin-1-yl)carbonyl)ethenyl)phenyl)sulfide; (2-Ethoxyphenyl )-[2-chloro-4(E-f (3-ethoxycarbonylpiperid in-1 -yl Jcarbony l]ethenyl )pheny l]sulf ide; (2-ElhoxyphenylH2-chloro-4(E-((4-carboxypiperidin-1-yl)carbonyl]ethenyl)phenyl]sulfide; (Benzodioxan-6-yl){2-chloro-4-(E-((4-acetylpiperazin-1-yl)carbony!)ethenyl)phenyl)sulfide; (2-lsopropylphenyl)[2-nitro-4-(E-((4-ethoxycarbonylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-lsopropylphenyl)[2-nitro-4-(E-((4-isopropoxycarbonylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-lsopropylphenyl)[2-nitro-4-(E-((4-isobutoxycarbonylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-lsopropylphenyl)[2-nitro-4-(E-((4-((1-propen-2-oxy)carbonyl)piperazin-1-yl)carbonyl)ethenyl)pheriy|[ sulfide; (2-lsopropylphenyl)[2-nilro-4-(E-((4-propionylpiparazin-1-yl)carbonyl)ethenyl)phenyllsulfide; (2-lsopropylphenyl)[2-nitro-4-(E-((4-carboxamidoptperazin-1-yl)carbonyl)eihenyl)phenyl]sulfrde; (2-lsopropylphenyl)[2-nitro^£-({4-m8thylaminocarbonylpipera2in-1-yl)cartioriyl)ethenyl)phenyllsulfide; (2-lsopropylphenyl)[2-nitro^-(£-((4-(pyrimidin-2-yl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-lsopropylphenyl)[2-nitro-4-(£-((4-hydroxyacetylpiperazin-1-yl)carbonyl)ethenyl)phenylIsulfide; (2-lsopropylphenyl)[2-nitro^-(EK{4-(pyrazine-2-carbony!)piperazin-1-yl)cart>onyl)ethenyl)phenyl]sulfide; (2-lsopropylpheny I )[2-trifluoromethyl-4-(E-({(2-carboxypyrrol-3-in-1 -yl )carbony I Jetheny I )phenyl]sulfide; {2-tsopropylphenyl)[2-nitro-4-(E-((3-hydroxyrnethyl-4-methylpiperazin-1-yl)carbonyl)eihenyl)phenyl]sulfide; (2-lsopropylphenyl)[2-trifluorornethyM-{£-(((2-carboxypyrrol-3-in-1-yt)carbonyl)ethenyl)phenyl]sulficle; (2-lsopropytphenyl}[2-triffuoromethyM^E-(((2-^ (2^sopropylphsnyl)(2^itro^^£^(3^^ethylamitH>carbonyl^pefazin-1-yi)caTbonyl)ettienyl)phenyl]sulfide; (2-lsopropylphenyl)(2-nitro-4-(E-(({3-cyclopropylaminocarDonyl)piperazin-1-yl)cart)onyl)ethenyl)phenyl] sulfide; {2-lsopropylphenyt)[2-nitro-4-(£-({3-carboxamidopiperazin-1-yl)carbonyl)©lhenyl)phenyl]sulfide; (2-lsopropytphenyl)[2-nitro^-(E-((3K;arbomethoxy-4-oxoppperidin-1-yl)carbonyl)elhenyl)phenyl]sulfide; (2-lsopropy'phenyl)[2-nilro-4-(£-((3,5-dinielhylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (1-Ethylindol-7-yl)[2-chloro-4-(£-({4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (3-I2-Methoxy]ethoxyphenyl)-[2-chloro-4{£-[(morpholin-1-yl)carbonytIethenyl)phenyl]sulfide; (2-Bromophenyl)(2-chloro-4-(£-((4,4'-S-dioxythiomorpholm-1-yl)carbonyl)elhenyl)phenyl]sulfide; (2-Bromophenyl)[2-chloro^-{£-{NK;arbomethoxymethyl-N-(3-{pyrrolidin-2-on-1-yl)prop-1-yt)amino)carbonyl) ethenyl)phenyl]sulfide; , (2-Bromophenyl)(2-chloro-4-{e-((4-S-oxythiomorpholin-1-yl)-2-pyrrolidinone)carbonyl)elhenyl)phenylj sulfide; (2-Methoxy-5-chlorophenyl)(2-nitro-4-(£-({4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyllsulfide; (2-lsoprapylphenylJ(2^itro^-(E-((3-acetoxymethyl)pip0razin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-lsopropylphenyl)[2-nitro^-{£-((3,5^imethyl-4acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (1-Methylindol-5-yl)[2-chloro-4-(E-((4-acelylpipGrazin-1-yl)carbonyl)efhenyi)phenyl]sulfide; (Benzodioxan-6-yl)[2-nilro-4-(f-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (Benzodioxan-6-yl)[2-nitro^-(£-((3-(pynrolidin-2H3n-1-yl)prop-1-ylamino)carbonyl)ethenyl)phenyl]sulfide; (Benzodioxan^-yl}[2-mtro^-(£K(3-caiboethoxypiperkJin-1-ylH:artJonyl)ethenyl)phenyl]suinde, (Benzodioxar)-6-yl)f.2-nitro-4-{£-((4-carboethoxypiperidin-1-yl)carbonyl)ethenyl)ptienyl]sulfide; (2-Ethoxyphenyl)[2-trifluoromethyl-4-{Z-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-Ethoxyphenyl)[2-irifluoramethyl-4-(£-((6-methylpyrid-2-ylamino)carbonyl)ethenyl)phenyllsuiridB; (2-Methyl-3-chlorophenyl)[2-nitro-4-(£-{(4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyi)sulfide; (Benzodioxan-6-yl)[2-nitro-4-(£-({3-carboxamidopiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide; {Benzodioxan-6-yl)[2-nitro-4-(£-{(2-carboethoxypiperidin-1-yl)carbonyl)ethenyl)pheny)]sulfide; (Benzodioxan-6-yl)[2-nitro-4-{£-((4-carboxamidopiperidin-1-yl)carbonyl)elhenyl)phenyl)sulfide; (Benzodioxan-6-yl)[2-nitro-4-(£-((4-(ert-butoxycarbonylpiperazin-1-yl)cart)onyl)ethenyl)phenyl]sulfide; (2-lsopropylphenyl)(2-nitro-4-(£'-((syn-3,5-dimethylmorpholin-1-yl)carbonyl)ethenyl)phenyl]sulfid6; [2-lsopropylpheny))(2-nitro-4-{£-({anti-3,5-dimathylmorpholin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2'isopropylphenyl)|2-nitro-4-(£-({3-carbo6thoxypiperazin-1-yl)carbonyl)efhenyl)phenyl]sulfide; (2-lsopropylphenyl)[2-nifro^-(£-{(3-isopropoxycarbonylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-lsopropylphenyl)[2-nitro^-(£-((3-(dimethylairiinocartionyl)-4-methylpiperazin-1-yl)carbonyl)ethenyl)phe-nyl]sulfide; (2-lsopropylphenyl)[2-nitro^-(£-((3-carbomelhoxy-4-hydroxypiperidin-1-yl)carbonyl)ethenyl)phefiy)]sulfide; {2-lsopropylphenyl)[2-nitro^-(£-((3-hydroxymethyl^-hydroxypiperidin-1-yl)carbonyl)et(ienyl)phenyl]sulfide; (2-Ethoxyphenyl)(2-)rifluoromethyM-(£-((2-i^rbomethoxy^-(methoxycarbonyl^iperazin-1-yl)carbonyl)eihe- nyl)phenyl]sulfide; (2-Effioxyphenyl)(2-trinuoromethyl-4-(£-((2-carbomethoxy-4-methyl piperazin-1-yl)cart)onyl)ethenyl)phenyl] sulfide; (2-Ethoxyphenyl)[2-frifiuoromemyl-4 phenyljsulfide; {lndol-6-yl)[2-chloro-4-(£-({4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (1-Ethyl.3-(dimethylaminomethyl)indol-7-yl)[2-chloro^-(£-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)pheriyl] sulfide; (5-Ethoxyb6nzodioxan-6-yl)[2-chloro-4-{£-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-Ethyl-4-bromophanyl)[2-nitro-4-(£-((4-acetylpipera2in-1-yl)carbonyl)ethenyl)phenyl]sulfide; (Benzodioxan-6-yl)(2-nilro-4-(£-({2-carboxypiperidin-1-yl)carbonyl)ethsnyl)phenyl]sulfide; (Benzodioxan-6-yl)[2-nitro-4-{E-((4-carboxymethylpiperazin-1-yl)carbQnyl)ethenyl)phenyl]sulfide; (3-Morpholinophenyl)I2-nitro-4-(£-{(4-acetylpiperazin-1-yl)carbonyl}ethenyl)phenyl]sulfide; (5-Ethoxybenzodioxan-8-yl)I2-cbtoro-4-(£-({4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenylIsulfide; (5-Chloro-8-ethoxyquindin-7-yl)[2-chloro-4-(e-({4-acetylpiperazin-1-y))carbonyl)ethenyl)phenyl)sulfide; (2-lsopropylphenyl)[2-nifro^-(E-((3-carboethoxypiperidin-1-y))carbonyl)ethenyl)phenyl]sulfide; (2-lsopropylphenyl)[2-nitro-4-(£-{{3-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-lsopropylphenyl)f2-nitro-4-{E-(((3-ethanesulfonylaminocarbonyl)piperidin-1-yl)carbonyl)ethenyl)phenyl] sulfide; (2-lsopropylphenyl)[2-nitro-4-{£-(((3-(4-methylpiperazine) sulfonylaminocarbonyl)piperidin-1-yl)carbonyl) ethenyl)phenyl]sulfide; (2-lsopropylphenyl)[2-nitro^-(£-(({3-p-toluenesulfonylaminocarbonyl)piperidin-1-yl)carbonyl)ethenyl)phenyl] sulfide; (2-lsoprapylphenyl)[2-nitro-4-(£'-{{3-methyl-4-acetylpiperazirt-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-Hydroxyphenyl)-[2-chloro-4(£-[{morpholin-1-yl)carbonyl]ethenyf)phenyl]sutfide {1-(Carboxymethyl)indol- 5-yl)[2-chloro-4-(£-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (Benzodioxan-6-yl)(2-trifluoromethyl-4-(e-((4-acetylpip8razin-1-yl)carbonyl)etheny()phenyf]sulfide; (2-lsopropylphenyl)[2-nitro-4-(E'-((3-(1-pyiTolidin-2-onyl)prop-1-ylanfiino)carbonyl)ethsnyl)pfienyllsulfide; (3-(2-Mon3holinoethylamino)phenyl)[2-trifluoromefhyl-4-(£-{(4-acetylpiperazin-1-yl)carboriyl)etbenyl)phenyl] sulfide; (2-Pyrrolidin-1-ylphenyl)(2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (3-Bromophenyl)[2-nitro-4-(£-({3-carboethoxypyi-rolidin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (3-Bromophenyl)[2-nitro-4-{£-((4-carboethoxypyrrolidin-1-yl)carbonyl)elhenyl)phenyl]sulfide; (2-(Hydroxymethyl)-benzadioxan-6-yl)[2-ctiloro-4-(£-((4-acetylpiperazin-1-yl)carbonyl)ettienyl)phenyl] sulfide; (Benzodioxan-6-yl)[2-trifluoromethyl-4-{£-({3-(pyrrolidin-2-on-1-yl)prop-l-ylamino)carbonyl)ethenyl)phenyl] sulfide; (3-(Dimethylaminomethyl)indol-5-yl)l2-chloro-4-(H-{(4-acety1piperazin-1-yl)carbonyl)ethenyl)phenylJsulfide; (2-lsopropylphenyl)[2-nitro-4-{E-((2-carboethoxypiperidin-1-yl)carbonyl)ethenyl)pbenyl]sulfide; (2-lsopropylphenyl)[2-nitro-4-(£-((2-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-lsoprt^)ylpher>yl)[2-nitro-4-(£-{(4-carboetfioxypiperidin-1-yl)carbonyl)elhenyl)phenyl]sulfide; (2-lsopropylphenyl)[2-nitro-4-(£-((4-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-lsopropylphenyl)[2-nitro^-(£-({{4-p-toluenesulfonylaminocarbonyl)piperidin-1-yl)carbonyl)ethenyl)phenyl] sulfide; (2-lsopropylphenyl)[2-nitro-4-(£-({3-carboxy-4-hydroxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (Benzodioxan-6-yl)(2-lrifluoromethyl-4-(£-((3-carboethoxypiperidin-1-yl)carbonyl)ethenyl)phenylJsulfide', (Benzodioxan-6-yl)[2-trifluoromethyl-4-(£-((2-carboethoxypiperidin-1-yt)carbonyl)ethenyl)phenyl]sulfide; {Benzodioxan-6-yl)[2-nitro-4-(£-((4-carboxypiperidin-1-yl)carbonyl)eIheny!)phenyl]sulfide; (Benzodioxan-6-yf)I2-trifluoromethyl-4-(£-((3-carboxypyrrolidin-1-yl)carbonyl)efhenyl)pherjyl]sulfide; (Benzodioxan-6-yl)[2-trifluoromethyl-4-(E-((4-carboethoxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (Benzodroxan-6-yl)f2-trifluorome(hyf-4-(£'-((2-caff3omefhoxy-4-/ef/-butoxycart)ony(pipe razin-1 -yljcarbonyf) e(henyl)phenyl]sulfide; (Benzodioxan-6-yt)[2-frifluoroniethyl-4-(£-({2-cartK>methoxy^-niethoxycarbonylpiperaziri-1-yl)carbonyl) ethenyl)phenyllsulfide; (Benzodioxan-6-yl)[2-trifluoromethyl-4-{£-((2-carbomethoxypiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-Methyl-3-{carboethoxymethyl)indol-5-yl)[2-trinuorom^^ sulfide; (1-(2-Me!hoxyethyl)indol-5-yl)[2-chloro-4-(£-{(4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyllsulfide; (2-lsopropylphenyl)l2-nitro^-(£-{(3-acetoxymethyl-4-hydroxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-lsopropylphenyl)[2-nitro-4-(£-((3-(dimethylaminocarbonyl)-4-hydroxypiperidin-1-yl)carbonyl)ethenyl)phe- nyljsulfide; (2-lsopropylphenyl)[2-nitro-4-(£-((3-cyanomorpholin-1-yl)carbonyl)elhenyl)phenyl]sulfide; (2-)sopropylphenyl)[2-nttro-4-{E-((3-carboethoxymorpholin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-lsopropylphenyl)(2-nitra-4-(£-((3-(tetrazol-5-yl)morpholin-1-y!)carbonyl)ethenyl)phenyl]sulfide; (Ben2odioxan-6-yl)[2-trif(i]oromethyl-4-(e-((4-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (Benzodioxan-6-yl)l2-lrifluorDmethyMK^-((2-cart)oxypiperklin-1-yl)cart>onyt)ethenyl)phenyllsulfide; (Benzodioxan-6-yl)[2-trinuoromethyM-(£-((4-carbome1hoxypiperazin-1-yl)carbonyl)ethenyl)phenylJsulfide; (Benzodioxan-6-yl)[2-lrifluoromethyl-4-(£-((3-aza-6,9-diooxaspiro[5,4]decan-1-yl)carbonyl)ethenyl)pheny!l sulfide; {Benzodioxan-6-yl)I2-trifluora-^-{E-((4-{bonzimidazolon-1-yl)ptperidin-1-yl)carbonyl)ethenyl)pheny(lsulfide; (Benzodioxan-6-yl)[2-trifluoromethyl-4-(E-((4-(methylaminocarbonyl)piperidin-1-yl)carbonyl)elhenyl)phenyll sulfide; {Benzodioxan-6-yl)[2-trifluoromethyM-(E-({3-carbomethoxy-4-methoxycarbonylpiperazin-1-yl)carbonyl) ethenyl)phenyl]sulfide; (2-lsopropylphenyl)[2-nitro-4-(F-((3-carboxymorpholin-1-yl)carbonyl)ethenyl)phenyllsulfide; (Benzodioxan-6-yl)[2-trifluoromeIhyl-4-(E-{(2-carboxy-4-methoxycarbonylpiperazin-1-yl)carbonyl)ethenyf) phenyl]sulfide; (Benzodioxan-6-yl)(2-trifluoromethyl-4-(£-((morpholin-1-yl)cartx)nyl}ethenyl)phenyl]sulfide; (Benzodioxan-6-yl)[2-trif1uoromethyl-4-(E-((4-(pyiTolidin-1-yl)piperidin-1-yl)carbonyl)Btheny!)phenyl]sulfide; (2-lsopropylphenyl)(2-nitro-4-(£-((3-aza-6,9-diooxaspiro[5.4]decan-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-lsopropylphenyl)[2-nitro-4-(£-({2-(dimelhylaminome;hyi)piperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-lsopropylphenyl)[2-nitra-4-(E-((piperidin-1-ylamino)carbonyl)elhenyl)plienyl]sulfide; (Benzodioxan-6-yt)[2-trifluoromethyl-4-(E-((3 phenyl]sulfide; {2-(Dimethylaminocarbonyl)-benzodioxan-6-yl)[2-chloro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phe- nyljsulfide;; (2-lsopropylphenyl )[2-nitro-4-(E-{(3-(2-(methoxymethyl )tetrazol-5-yl )piperidi n-1 -yl Jcarbony I )ethenyl)phenyl] sulfide {2-lsopropylphenyl)[2-nitro-4-(£-{(3-(1-(methoxymethyl)tetrazol-5-yl)piperidin-1-yl)carbonyl)ethenyl)phenyl] sulfide; (1-Methyllndol-5-yl)[2 (2-lsopropylphenyl)[2-nitro-4-{E-((3-(tetrazol-5-yl)piperidin-1-yl)carbonyt)eihenyl)phenyl}sulfide; (1-Methylindol-5-yl)[2-chloro^-(£-((3-carboethoxypiperidin-1-yl)carbony1)ethBnyl)phenyl]sulfide {1-Methylindol-5-yl)|2-chloro-4-(£-((3-carboxypiperidin-1-yl>carbonyl)ethenyl)phenyl]sulfide; (1-Methylindol-5-yl)[2-chloro-4-(E-((4-carboethoxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (1-Methylindol-5-yl)[2-chloro-4-(£-((3-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-lsopropylphenyl)[2-nitro^-(E-({2-(1-methylpyrrolidin-2-yl)ethylarnino)carlionyl)ethenyl)phenyl]sulfide; (2-lsopropylphenyl)[2-nitro-4-(E-((4-(pyrrolidin-1-yl)piperidin-1-yl)carbonyl)ethenyl)phenyl]sulfkle; (2-lsopropylphenyl )[2-nitro-4-(£-((4-sulfopiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-lsopropylphenyl )|2-nitro-4-(£-({3-hydroxypiperidtn-1-yl)carbonyl)ethenyl)phenyl]sulfide; (Benzodioxan-6-yl)[2-trifluoromethyl-4-(E-((3-((ethanesulfonylamino)carbonyl)piperidin-1-yl)carbonyl)ethe- nyl)phenyl)suiride; (Benzod»xan-6-yl)[2-trifluoromethyl-4-(E-((3-((p-toluenesulfonylamino)carbonyl)piperidin-1-yi)carbonyl) ethenyl)ptienyl] sulfide; (Benzodioxan-B-yl)I2-trifluoromethyl-4-(£-((4-((ethanesulfonylamino)carbonyl)piperidin-1-yl)carbonyl)ethe- nyt)pheny I [sulfide; (Benzodtoxan-6-y1)[2-trifluoromethyl-4-(E-((2(tetrazol-5^ (2-lsopropylphenyl )[2-nitro-4-(E-((2-buty1, 5-(tetrazol-5-yl)morpholin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2- sulfide; (2-{and3-)(Hydroxymethyl)-benzodioxan-6-y])[2-nitro-4-(E-((3-(pyrrolidin-2-on-1-yl)prop-1-ylarnino)carbonyi) ethenyOphenylJsulfide; (2-{and 3-)(Hydroxymethyl)-benzodioxan-6-yl)[2-trifluoramethyl-4-(E-((3-(pyrrolidin-2-on-1-yl)prop-1-ylarni- no)carbonyl)ethenyl)phenyl]sulfide; {3-Hydroxymethyl)-benzodioxan-6-yl)[2-nitro-4-(E-((3-(pyrrolidin-2-on-1-yl)prop-1-ylamino)carbonyl)ethenyl) phenyljsulfide; (Benzodioxan-6-yl)I2-chloro-4-(E-((3-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl] (2-(and 3-) (2-lsopropylphenyl)[2-nitro^-(£-((3-(methylaminocail3onyl)morpholin-1-yl)carbonyl)ethenyl)phenyl]sulfide: (2-lsopropylphenyl)[2-nitro^-(E-((3-(hydroxymethyl)morpholin-1-yl)carbonyl)6thenyl)phenyl]sulfide; (2-lsopropylphenyl)[2-nitro-4-(£-((3-{aceloxymethyl)morpholin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-lsopropylphenyl)[2-nitro-4-(E-((3-(aminomeihyl)morpholin-1-yl)carbonyl}ethenyl)phenyl]sulfide; (BenzcxJioxan-6-yl)[2-chloro-4-(E-((3-(pyrrolidin-2-on-1-yl}prop-1-ylamino)carbonyl)ethenyl)phenyl]sijlfida; (2-MethoxyphenylH2,3-dichtoro-4(E-[(morpholin-1-yl)cartx)nyt]ethenyl)phenyl]sulfide; (2-Methoxyphenyl )-[2,3-dimethy!-4(E-[(morpholin-1 -yl )carbony I] ethenyl )phenyl]sul fide; (2-lsopropylphenyl)[2-nitro-4-(E-{{indol-5-ylamino)carbonyl)8thenyl)phenyl)sulfide: (Benzodioxan-6-yl)[2-chloro-4-(E-({3-carboxypiperidin-1-yl)carbonyl}ethenyl)phenyl]sulflde; (Benzodioxan-6-yl)[2-chloro-4-(E-({3-{tetrazol-5-yl)piperidin-1-yl)carbonyl)ethenyl)phenyllsulfide; (Benzodioxan-6-yl)|2-chloro-4-(E-({4-(/ert-butoxycarbonyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (Benzodioxan-6-yl)[2-chloro-4-(E-((2-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulflde; (Benzodioxan-6-yl)[2-chloro-4-(E-((3-(tetrazol-5-yl)morpholin-1-y!)carbonyl)ethenyl)phenyl]sulfide; (Benzodioxan-6-yl)[2-chloro-4-(E-((4-(methylaminocarbonyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-Methoxyphenyl )-[2,3-dichloro-4{E-[(4-carboxypipsridin-1-yl)carbonyl]ethenyl)pbenyl)sulfide; (2-Methoxyphenyl H3-chloro-4(E-[(morpholin-1-yl)carbonyl]ethenyl)phenyl]sulfide; (2-lsopropylpheny I )(2-n itro-4-(E-((4-oxopiperid in-1 -yl )carbony I )ethenyl )phenyl]sulf ide; (Benzodioxan-6-yl)[2-trifluoromethyl-4-(E-{(3-R-carboelhoxypiperidin-1-yl)carbonyl)ethenyl)phenyl] sulfide; (Benzodioxan-6-yl)[2-trif)uoromethyl-4-{E-{(3-ff-cart)oxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (Benzodioxan-6-yl)[2,3-dichloro-4-(E-((3-(pyrrolidin-2-on-1-yl)prop-1-ylamino)carbonyt)ethenyl)phenyll sulfide; (Benzodioxan-6-yl)[2,3-dichlora-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyllsulfide; (Benzodioxan-6-yl)[2,3-dichloro-4-(E-((3-carboethoxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (Benzodioxan-6-yl)[2,3-dichloro-4-(E-((4-carboethoxypiperidin-1-yl)carbonyl}ethenyl)phenyl]sulfide; (Benzodioxan-6-yl )[2,3-d ichloro-4-(E-((3-carboxypiperidin-1 -y I )carbonyl)etheny I )phenyl Jsulftde; (Benzod ioxan-6-y I )(2, 3-dichloro-4-(E-((4-carboxypiperid in-1 -y I )carbonyl)etheny l )phenyl)sulf ide; (2-lsopropylphenyl)[2,3-dichloro-4-(E-((3-(1-pyrrolidin-2-onyl)propylamino) carbonyl)ethenyl)phenyl|sulfide; (2-lsopropylphenyl)[2,3-dichloro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-lsopropylphenyl)[2,3-dichloro-4-(E-((3-carboelhDxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-lsopropylphenyl)[2,3-dichloro-4-(E-((4-carboethoxypiperidin-1-yl)carbonyl)6thenyl)phenyl]sulfid©; (2-lsopropylphenyl)[2,3-dichloro-4-(E-((3-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-lsopropytphenylX2,3^ichloro^^E-((4^arboxypiperidin'1-yl)carbony (1-Methylindol-5-yl)[2,3-dichloro-4-(E-((3-carboelhoxypipeiidin-1-yl)carbonyl)ethenyl)phenyllsulfide; (1-Methylindol-5-yl)[2,3-dichloro-4-(E-((3-carboxyptperidin-1-yl)carbonyl)ethenyl)phenyllsulfide; (1-Methylindol-5-yl)(2,3-dichloro-4-(E-((4-carboelhoxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (1-Methylindol-5-yl)[2,3-dichloro-4-(E-((4-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-Ethoxyphenyl)-[2.3-dichloro-4(E-[(4-carboxypiperidin-1-yl)carbonyl]ethenyl)phenyl]sulfide; (2-Ethoxyphenyl )-[2,3-d ichloro-4{E-[(morpholin-1 -y I )carbonyl]ethenyl )phenyl]sulf ide; (2-Ethoxyphenyl)-[2,3-dichloro-4{E-[(3-carboxypipendin-1-yl)carbonyl]ethenyl)phenyl]sulfide; (2-lsopropylphenyl)[2-nitro-4-(E-((3-carboethoxypyrrolidin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-lsopropylphenyl)[2-nitro-4-(E-((3-carboxypyrro1idin-1-yl)carbonyl)ethenyl)phenyllsuiride; (2-lsopropylphenyl)(2.3-difluoro-4-(E-({3-carboethoxypiperidin-1-yl)carbonyl)ethenyl)phenyl)sulfide; (2-lsopropytphenyl)[2,3-difluoro-4-(E-{(3-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-lsopropyfphenyl)[2.3-difluoro^-(E-((4-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (Benzodioxan-6-yl)[2-trifIuoromelhyl-4-(E-((3-ethoxycarbonylpyn-olidin-'f-y()carbonyfJetheny()phenylIsuffide (8enzodioxan-6-yl)[2-trifluoromethyM-(E-((3-carboxypyrrolidin-1-yl)cart>onyl)ethenyl)phenyl]sulfide; (2-Methoxyphenyl )[2-chloro-3 -trifluoromethyl-4-(£-({4-carboethoxypiperidin-1-yl)cartonyl)ethenyl)phenyl] sulfide: (2-Methoxy phenyl )I2-chloro-3-trifluoromethyl-4-(£-((4-carboethoxypiperidin-1-yl)carbonyl)ethenyl)phenyl) sulfide; (2-Methoxypheny()[2-chloro-3-trifluoromethyl-4-(£-{(rnorpholin-1-yl)carbonyl)ethenyl)phenyllsulfide; (Benzodioxan-6-yl) [4-(£-((4-carboxypiperidin-1-yl)carbonyl)ethenyt)naphthyl] sulfide; (2-Methoxypheny)) [2,3-dicWoro-4-(f'-({4-{spiro-hydan(oin-5-yl)-piperidifi-1-yl)c8rbonyt)ethenyl)pheny(] sulfide: (2-Methoxypheny!) I2,3-dichloro-4-(E-(4-(2-(2-hydroxyethoxy)ethyl)piperazin-1-yl)carbonyl}ethenyl)phenyl| sulfide: (2-Methoxyphenyl)[2,3-dichloro-4-(E-((4-ethylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-lsopropylphenyl)[2,3-dichloro-4-(E-((4-(2-(2-hydroxyethoxy)ethyl)piperaztn-1-yl)carbonyl)ethenyl)phenyl] sulfide: (Benzodioxan-6yl)[2,3-bis(trifluoromathyl)-4-(£-{(4-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyljsulfide; (2-Methoxyphenyl) [2,3-dichloro-4-(E'-((4-(carboxymethylamino)cart)onyl-pip9ndin-1-yl)carbonyl)ethenyl) phenyl]sulfide; (2-Methoxyphenyl) [2.3-bis(trifluoromethylM-(£-((4^arboxymethylpiperazin-1-yl) carbonyl)ethenyl)phenyl] sulfide; (2-Methoxyphenyl)[2.3-bis(trifluoromethyl)-4-(E-((4-N-(2-hydroxyethyl)piperazin-1-yl)carbonyl)ethenyl>phe- nyljsulfide; (1-Methylindol-5-yl)[2,3-dichloro-4-(E-((4-(carbo-2,3-dihydroxypropylamino)piperidin-1-yl)carbonyl)ethenyl) phenyljsulfide; (2-Methoxyphenyl) [2,3-dichloro-4-(E-(4-(2,3-dihydroxypropionyl)piperazin-1-yl)carbonyl)ethenyl)phenyl] sulfide; (2-Methoxyphenyl) [2,3-dichloro-4-(E-(4-(2,3-dihydroxy-3-carboxypropionyl)piperazin-1-yl)carbonyl)ethenyl) phenyl]sulfide; (t-Methylindol-5-ylH2,3-dichloro-4-(E-((4-(carboxymethylamino)cartx)nylpiperidin-1-yl)carbonyl)ethenyl)phe- nyljsulfide: (1-Methylindol-5-yl)[2,3-dichloro-4-(E-(4-tetrohydrofuroylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-Methoxyphenyl) [2,3-dichloro-4-(E-((4-amino-4-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-Methoxyphenyl )[2,3-dichloro-4-((4-furoylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (1-Methylindol-5-yl)I2,3-dichloro-4-(E-{4-(carbo-3-sulfopropylamino)piperadin-1-yl)carbonyl)ethenyllphenyl] sulfide; {2-Methoxyphenyl)[2,3-dichloro-4-(E-(4-acetylamino-4-carboxypiperidin-1-ylcarbonyl)ethenyl)phenyllsulfide; (2-Mettioxyphenyl}[2,3-bis(trifluoromethy(H-(E-((4-carboxypipendln-1-yl)carbonyf)ethenyt)phenyfJs^ (2-Methoxyphenyl) 5-[8-(E-((4-(aminocarbonyl)piperidin-1-yl)carbonyl)ethenyl)quinolinyl3sulfide: (2-Methoxyphenyl) [2-trifluoromethyl-4-(E-((4-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide: (1-Methylindol-5-yl)I2,3-dichloro-4-(E/2-((1S,4S)-2,5-diazabycyclo(2,2,1)heptan-2-ylcarbonyl)ethenyl)- 2,3-dichlorophenyl]sulffde; (1-Methylindol-5-yl)I2,3-dichloro-4-(E-(4-hydroxy-3-carboxypiperadin-1-ylcarbonyl)ethenyl)phenyl]sulfide;; (1-Methylindol-5-y!)(2,3-dichloro-4-(E-(S-oxothiomorpholin-1-ylcarbonyl)ethenyl)phenyllsulfide: (2-Methoxyphenyl) [2,3-dichloro-4-(£-((4-sulfophenylamino)cart)onyl)ethenyl)phenyl]sulfide; (2-Methoxyphenyl) I2,3-dichtoro-4-(E-((4-carboxyphenylamino)carbonyl)ethenyl)phenyl]sulfide; and [3-{4-Morpholino)phenyl][2,3-dichloro-4-(E-((4-carboxypiperidin-1-yl)carbonyl]ethenyl)phenyl]sulfide. 13. A cinnamide compound according to Claim 1 selected from: (2-Formylphenyl)[2-nitro-4-{E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-€thoxyphenyi)-[2-chloro-4(£-[(morpholin-1-yt)carbonyl]ethenyl)prienyl]sulfide; (2-lsopropylphenyl)[2-nitro-4-(E-((3-dimethylaminocarbonyl-4-acety!pinerazin-1-yl)cart)onyl)etrienyl)phenyl] sulfide; (2-lsopropylphenyl)12-nitro^-(E-((4-methoxycarrx)nylpiperazin-l-yl}carbonyl)ethenyl)phenyllsulfide; (2-Ethoxyheny!)f2-trifluoromethyl-4-(E-({2-carboxy-^ nyl]sulfide; {2-E1hyl-4-bromophenyl)[2-nitro-4-(£-{(4-acetylpiperazin-1-yl)carbonyl)ertienyl)phenylJsulfide; {3-Morpholinophenyl)[2-nitro-4-(E-{(4-acetylpinerazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; {2-lsopropylphenyl)[2-nitro-4-(E-((3-carboetrioxypiperidin-1-yl)carbonyl)ethenyl)prienyllsulfide; (2-lsopropylphenyl)(2-nitro^E^(3^1^yrrolidir^2-onyl)pro (2-{Hydroxymethyl)-benzodioxan-6-yl)(2-chloro-4-(E-({4-acetylpiperazin-1-yl)carbonyl)ettienyl)phenyt] sulfide; {Benzodioxan-6-yl)[2-trifluoromethyl-4-(E-{(3-carboxypyrrolidin-1-yl)carbonyl)eitienyl)prienyllsulfide; (Benzodioxan-6-yl)(2-trifluoromethyi-4-(S((4-carboethoxypiperidin-l-yl)carbonyl)ethenyl)phenyl]sulfide; {Benzodioxan-6-yl)[2-trifluorarnethyl4-(£-((2-carbomethoxy-4-melrioxycarbonylpiperazin-1-yl)carbonyl)ethe- nyl)phenyl]sulfide; (Berttodioxan^-yl)[2-trifluorornethyl-4-(E-((2-carbomethoxypiperazin-1-yl)carbonyl)ethenyl)phenyl)sulfide; (Benzodioxan-6-yl)[2-chloro^-(E-((4-(methylaminocarbonyl)p^ (2-Me!hoxy phenyl )-[2,3-dichloro-4(E-[{4-carboxy piperidin-1 -yl )carbonyl]ethenyl Jpheny IJsulf ide; (Benzodioxan^-yl)[2-trifluoromethyM-(E-{(3-R-carboethoxypiperidin-1-yl)cart)onyl)ethenyl)phenyl]sul(ide; (Benzodtoxan-G~yl)l2,3 sulfide; (Benzodioxan-6-yl)[2,3-dichlo^o-4-(E^(4-acetylpipe^azin-1-yl)ca^bo^y^)ethenyl)phenyl]sulflde; (Benzodioxan-6-yl)[2,3-dichloro-4-(E-((3-carboethoxypioeridin-1-yl) carbonyl )etheny I Jpheny l]sulfide; (BenzcKjioxan-6-yl)(23-dichloro^-(E-((4-cartoethoxypiperidin-l-yl)carbonyl)ethenyl)phenyl]sulfide; (BBnzodioxan-6-yl)I2,3-dichloro-4-(E-((3-carboxypiperidin-1-yl)carbonyl)elhenyl)phenyllsulfide; (Benzodioxan-6-yl}[2,3-dichloro-4-(E-((4-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-lsopropylphenyl)[2,3Hdichloro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyllsulfide; (2-lsopropylphenyl)[2,3Hdichlora-4-(E^(3-carboethoxypiperidin-1-yl)carbonyl)ethenyl)phenyl]suiride; (2-lsopropylphenyl)[2,3-dichloro-4-(E-((3-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide; (2-lsopropylphenyl)l2.3-dichloro-4-{E-({4-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyllsulfide; (2-Methoxyphenyl) (2,3^ichtoro^^E-((4-(cafboxymethylamino)carbonyl-piper(din-1-yl)carbonyt)e(heriyl) phenyljsulfide; (2-Methoxyphenyl)[2,3-bis(trifluoromethyl)-4-(E-((4-carboxymethylpipera2in-1-yl) carbonyl)ethenyl)phenylJ sulfide; and {2-Methoxyphenyl)(2.3-bis(trifluoromemyl)-4-(E-((4"N-(2-hydroxyethyl)piperazin-1-yl)cartH3nyl)ethenyl)phe- nyl]sulfide. 14. A cinnamide compound according to Claim f wherein Arts selected from the group consisting of methoxypheny! andisopropylphenyl. 15. A cinnamide compound according to Claim 1 wherein Ar is benzodioxan or substituted benzodioxan. 16. A cinnamide compound according to Claim 1 wherein R3 is a "trans-cinnamide"; and Ar is selected from 1,3-benzimidazol-2-one, 1,4-benzodioxane, 1,3-benzodioxole, 1-benzopyr-2-en-4-one, indole, isatin, phenyl, 1,3-quinazolin- 17. A cinnamide compound according to Claim 1 whereinR^andR^areindependentlyselectedfromhydrogen. alkyl, cycloalkyl, alkoxycarbonylalkyl. hydroxyalkyl, and heterocyclylalkyl. 1. A cinnamide compound according to Claim 1 wherein NR10Rn is heterocyclyl or substituted heterocyclyl. 3. A pharmaceutical composition comprising a compound of Claim 1 in a pharmaceutical!y-acceptable carrier. 0, A process for preparing a cinnamide compound of claim 1, which process comprises activating the acid group in a compound of the formula

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