US2005250768A1PendingUtilityA1
Cell adhesion-inhibiting antiinflammatory and immune-suppressive compounds

Assignee: ABBOTT LABPriority: Dec 29, 1998Filed: Aug 20, 2004Published: Nov 10, 2005
Est. expiryDec 29, 2018(expired)· nominal 20-yr term from priority
Inventors:James T. Link Gang Liu Zhonghua Pei Tom Geldern Martin Winn Zhili Xin Steven A. Boyd Gui-Dong Zhu Jennifer Freeman Indrani W. Gunawardana Michael A. Staeger Hwan-Soo Jae John Lynch Sheldon Wang
C07C 323/62A61K 31/495A61K 31/454C07D 211/60C07D 205/04C07D 241/04C07D 213/40C07D 249/08C07D 233/56A61K 31/496C07D 211/46C07D 295/185C07D 207/27C07D 213/81C07D 209/08A61K 31/537C07D 231/12A61K 31/54C07D 295/26C07D 217/06C07C 2601/02C07D 401/04C07D 211/20C07D 207/14C07D 207/09
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Claims
Abstract

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 methods of inhibiting inflammation or suppressing immune response in a mammal.
Claims

exact text as granted — not AI-modified
1 . A pharmaceutical composition comprising a compound of formula I  
     
       
         
         
             
             
         
       
     
     or a pharmaceutically-acceptable salt or prodrug thereof,  
     wherein R 1 , R 2 , R 3 , R 4 , and R 5  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 1  or R 3  is a “cis-cinnamide” or a “trans-cinnamide”, defined as  
                     
 wherein R 8  and R 9  are independently selected from 
 a. hydrogen, and  
 b. alkyl,  
 c. carboxy alkyl,  
 d. alkylaminocarbonyl alkyl, and  
 e. dialkylaminocarbonyl alkyl,  
 
 and R 10  and R 11  are independently selected from  
 a. hydrogen,  
 b. alkyl,  
 c. cycloalkyl,  
 d. alkoxycarbonylalkyl,  
 e. hydroxyalkyl,  
 f. substituted aryl,  
 g. heterocyclyl,  
 h. heterocyclylalkyl,  
 i. heterocyclylamino,  
 j. substituted heterocyclyl, and  
 k. substituted heterocyclylalkyl,  
 or where NR 10 R 11  is heterocyclyl or substituted heterocyclyl, where substituents are independently selected from 
 1) alkyl,  
 2) alkoxy,  
 3) alkoxyalkyl,  
 4) cycloalkyl,  
 5) aryl,  
 6) heterocyclyl,  
 7) heterocyclylcarbonyl,  
 8) heterocyclylalkylaminocarbonyl,  
 9) hydroxy,  
 10) hydroxyalkyl,  
 11) hydroxyalkoxyalkyl,  
 12) carboxy,  
 13) carboxyalkyl,  
 14) carboxycarbonyl,  
 15) carboxaldehyde,  
 16) alkoxycarbonyl,  
 17) arylalkoxycarbonyl,  
 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) alkylsulfonyl,  
 34) alkylsulfonylaminocarbonyl,  
 35) arylsulfonylaminocarbonyl, and  
 36) heterocyclylsulfonylaminocarbonyl,  
 and wherein Ar is a substituted aryl or substituted heteroaryl group, where substitutions are independently selected from  
 
 a. hydrogen,  
 b. halogen,  
 c. alkyl,  
 d. aryl,  
 e. haloalkyl,  
 f. hydroxy,  
 g. alkoxy,  
 h. alkoxyalkyl,  
 i. alkoxycarbonyl,  
 j. alkoxyalkoxy,  
 k. hydroxyalkyl,  
 l. aminoalkyl,  
 m. aminocarbonyl,  
 n. alkyl(alkoxycarbonylalkyl)aminoalkyl,  
 o. heterocyclyl,  
 p. substituted heterocyclyl,  
 q. heterocyclylalkyl,  
 r. substituted heterocyclylalkyl,  
 s. carboxaldehyde,  
 t. carboxaldehyde hydrazone,  
 u. carboxamide,  
 v. alkoxycarbonylalkyl,  
 w. carboxy,  
 x. carboxyalkyl,  
 y. carboxyalkoxy,  
 z. carboxythioalkoxy,  
 aa. carboxycycloalkoxy,  
 bb. thioalkyl,  
 cc. hydroxycarbonylalkyl (carboxyalkyl),  
 dd. hydroxyalkylaminocarbonyl,  
 ee. cyano,  
 ff. amino,  
 gg. heterocyclylalkylamino,  
 hh. carboxyalkylamino,  
 ii. heterocyclylalkylaminocarbonyl, and  
 jj. “trans-cinnamide,” 
 wherein the heterocyclyl is chosen from 4-, 5-, 6- and 7-membered rings containing 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur; the 4- and 5-membered rings have zero to two double bonds and the 6- and 7-membered rings have zero to three double bonds, the heterocyclyl being optionally substituted with alkyl, halogen, hydroxy or alkoxy substituents,  
 further wherein the heterocyclyl optionally comprises a group chosen from: 
 (i) bicyclic, tricyclic and tetracyclic groups in which any of the above heterocyclic rings is fused to one or two rings independently selected from an aryl ring, a cyclohexane ring, a cyclohexene ring, a cyclopentane ring, a cyclopentene ring, and another monocyclic heterocyclic ring;  
 (ii) bridged bicyclic groups where a monocyclic heterocyclic group is bridged by an alkylene group optionally selected from  
                     
 
 (iii) compounds of the formula  
                     
 where X* and Z* are independently selected from —CH 2 —, —CH 2 NH—, —CH 2 O—, —NH— and —O—, with the proviso that at least one of X* and Z* is not —CH 2 —, and Y* is selected from —C(O)— and —(C(R″) 2 ) v —, where R″ is hydrogen or alkyl of one to four carbons, and v is 1-3,  
 and a pharmaceutically acceptable carrier.  
 
   
   
       2 . A pharmaceutical composition according to  claim 1  wherein R 1  is a “cis-cinnamide” or a “trans-cinnamide”, and R 3  is hydrogen.  
   
   
       3 . A pharmaceutical composition according to  claim 1  wherein R 3  is a “cis-cinnamide” or a “trans-cinnamide”, and R 1  is hydrogen.  
   
   
       4 . A pharmaceutical composition according to  claim 1  wherein R 3  is a “cis-cinnamide” or a “trans-cinnamide”, and R 1 , R 8 , and R 9  are hydrogen.  
   
   
       5 . A pharmaceutical composition according to  claim 4  wherein R 3  is a “cis-cinnamide”.  
   
   
       6 . A pharmaceutical composition according to  claim 4  wherein R 3  is a “trans-cinnamide”.  
   
   
       7 . A pharmaceutical composition according to  claim 1  wherein R 3  is a “cis-cinnamide” or a “trans-cinnamide”, R 1 , R 2 , and R 4  are each independently hydrogen or alkyl; and R 5  is selected from halogen, haloalkyl, and nitro.  
   
   
       8 . A pharmaceutical composition according to  claim 4  wherein Ar is substituted aryl or substituted heteroaryl.  
   
   
       9 . A pharmaceutical composition according to  claim 4  wherein R 10  and R 11  are each independently selected from hydrogen, alkyl, cycloalkyl, alkoxycarbonylalkyl, hydroxyalkyl, and heterocyclylalkyl.  
   
   
       10 . A pharmaceutical composition according to  claim 4  wherein NR 10 R 11  is heterocyclyl or substituted heterocyclyl.  
   
   
       11 . A pharmaceutical composition according to  claim 8  wherein Ar is 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 pharmaceutical composition according to  claim 1  comprising a compound selected from the group consisting of: 
 (2,4-Dichlorophenyl)[2-(E-((6-hydroxyhexylamino)carbonyl)ethenyl)phenyl]sulfide;    (2,4-Dichlorophenyl)[2-(E-((3-(1-imidazolyl)propylamino)carbonyl)ethenyl)phenyl]sulfide;    (2,4-Dichlorophenyl)[2-chloro-4-(E-((2 hydroxyethylamino)carbonyl)ethenyl)phenyl]sulfide;    (2,4-Dichlorophenyl)[2-chloro-4-(E-((6 hydroxyhexylamino)carbonyl)ethenyl)phenyl]sulfide;    (2,4-Dichlorophenyl)[2-chloro-4-(E-((bis-(2-hydroxyethyl)amino)carbonyl)ethenyl)phenyl]sulfide;    (2,4-Dichlorophenyl)[2-chloro-4-(E-((3-(1-pyrrolidin-2-only)propylamino)carbonyl)ethenyl)phenyl]sulfide;    (2,4-Dichlorophenyl)[2-chloro-4-(E-((1-morpholinyl)carbonyl)ethenyl)phenyl]sulfide;    (2,4-Dichlorophenyl)[2-chloro-4-(E-((4-methylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2,4-Dichlorophenyl)[2-chloro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2,4-Dichlorophenyl)[2-chloro-4-(E-((4-(2-pyridyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-(Hydroxymethyl)phenyl)[2-chloro-4-(E-((1-morpholinyl)carbonyl)ethenyl)phenyl]sulfide;    (2-Bromophenyl)[2-chloro-4-(E-((1-morpholinyl)carbonyl)ethenyl)phenyl]sulfide;    (2,4-Dichlorophenyl)[2-chloro-4-(E-((4-(2-hydroxyethyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2,4-Dichlorophenyl)[2-chloro-4-(E-((4-(2-hydroxyethoxyethyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Bromophenyl)[2-chloro-4-(E-((3-(hydroxymethyl)piperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Bromophenyl)[2-chloro-4-(E-((2-(hydroxymethyl)piperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Bromophenyl)[2-chloro-4-(E-((3-acetamidopyrrolidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Bromophenyl)[2-chloro-4-(E-((4-hydroxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Bromophenyl)[2-chloro-4-(E-((piperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2,4-Dichlorophenyl)[2-chloro-4-(E-((3-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2,4-Dichlorophenyl)[2-chloro-4-(E-((4-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Bromophenyl)[2-chloro-4-(E-((4-acetylhomopiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Bromophenyl)[2-chloro-4-(E-((thiomorpholin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Bromophenyl)[2-chloro-4-(E-((4-(1-benzimidazol-2-only)piperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Bromophenyl)[2-chloro-4-(E-((2-etrahydroisoquinolinyl)carbonyl)ethenyl)phenyl]sulfide;    (2-Methylphenyl)[2-trifluoromethyl-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Methylphenyl)[2-trifluoromethyl-4-(E-((1-morpholinyl)carbonyl)ethenyl)phenyl]sulfide;    (2-Methylphenyl)[2-trifluoromethyl-4-(E-((2-(1-morpholinyl)ethylamino)carbonyl)ethenyl)phenyl]sulfide;    (2-Methylphenyl)[2-trifluoromethyl-4-(E-((4-phenylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; 
 (2-Methylphenyl)[2-trifluoromethyl-4-(E-((3-(1-pyrrolidin-2-onyl)propylamino)carbonyl)ethenyl)phenyl]sulfide;  
   (2-Methylphenyl)[2-trifluoromethyl-4-(E-((cyclopropylamino)carbonyl)ethenyl)phenyl]sulfide;    (2,4-Dichlorophenyl)[2-nitro-4-(E-((4-acetylpiperazin-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-Dichlorophenyl)[2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (4-Bromophenyl)[2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (4-Methylphenyl)[2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2,4-Dichlorophenyl)[2-nitro-4-(E-((4-(tert-butoxycarbonyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2,4-Dichlorophenyl)[2-nitro-4-(E-((4-(2-furoylcarbonyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2,4-Dichlorophenyl)[2-nitro-4-(E-((4-(methanesulfonyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2,4-Dichlorophenyl)[2-nitro-4-(E-((4-(diethylaminocarbonylmethyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2,4-Dichlorophenyl)[2-nitro-4-(E-((4-(diethylaminocarbonyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2,4-Dichlorophenyl)[2-nitro-4-(E-((4-(tert-butoxycarbonylmethyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2,4-Dichlorophenyl)[2-nitro-4-(E-((4-(carboxycarbonyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2,4-Dichlorophenyl)[2-nitro-4-(E-((4-(carboxymethyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Methylphenyl)[2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Chlorophenyl)[2-nitro-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)[2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Ethylphenyl)[2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-iso-Propylphenyl)[2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-tert-Butylphenyl)[2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Chlorophenyl)[2-chloro-4-(E-((4-acetylpiperazin-1-yl)carbonyl))2-propenyl)phenyl]sulfide;    (2-(1-Morpholinylmethyl)phenyl)[2-chloro-4-(E-((1-morpholinyl)carbonyl)ethenyl)phenyl]sulfide;    (2-(4-(1,3-Benzodioxolyl-5-methyl)piperazin-1-ylmethyl)phenyl)[2-chloro-4-(E-((1-morpholinyl)carbonyl)ethenyl)phenyl]sulfide;    (2-(4-(iso-Propylaminocarbonylmethyl)piperazin-1-ylmethyl)phenyl)[2-chloro-4-(E-((1-morpholinyl)carbonyl)ethenyl)phenyl]sulfide;    (2-((N-Ethoxycarbonylmethyl-N-methyl)aminomethyl)phenyl)[2-chloro-4-(E-((1-morpholinyl)carbonyl)ethenyl)phenyl]sulfide;    (2-Formylphenyl)[2-chloro-4-(E-((1-morpholinyl)carbonyl)ethenyl)phenyl]sulfide;    (2-(4-Formylpiperazin-1-ylmethyl)phenyl)[2-chloro-4-(E-((1-morpholinyl)carbonyl)ethenyl)phenyl]sulfide;    (2-(E-((1-Morpholinyl)carbonyl)ethenyl)phenyl)[2-chloro-4-(E-((1-morpholinyl)carbonyl)ethenyl)phenyl]sulfide;    (2-Formylphenyl)[2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Formylphenyl)[2-chloro-4-(E-((1-morpholinyl)carbonyl)ethenyl)phenyl]sulfide, N,N-dimethyl hydrazone;    (2-((3-(1-Morpholinyl)propyl)-1-amino)phenyl)[2-chloro-4-(E-((1-morpholinyl)carbonyl)ethenyl)phenyl]sulfide;    (2,4-Dichlorophenyl)[2-bromo-4-(E-((3-(1-pyrrolidin-2-only)propylamino)carbonyl)ethenyl)phenyl]sulfide;    (2,4-Dichlorophenyl)[2-formyl-4-(E-((1-morpholinyl)carbonyl)ethenyl)phenyl]sulfide;    (2-Chloro-6-formylphenyl)[2-chloro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Cyanophenyl)[2-chloro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-cyano-4-(E-((morpholin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Bromophenyl)[2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-(Pyrrolidin-1-yl)phenyl)[2-chloro-4-(E-((morpholin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Methoxyphenyl)-[2-chloro-4(E-[(morpholin-1-yl)carbonyl]ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-carbomethoxypiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Methylphenyl)[2-nitro-4-(E-((3-carboxamido-4-carbobenzoxypiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((2-carbomethoxy-4-tert-butoxycarbonylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((2-carboxy-4-tert-butoxycarbonylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-trifluoromethyl-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-trifluoromethyl-4-(E-((morpholin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-trifluoromethyl-4-(E-((3-(pyrrolidin-2-on-1-yl)prop-1-ylamino)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-trifluoromethyl-4-(E-((cyclobutylamino)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-trifluoromethyl-4-(E-((cyclopentylamino)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-trifluoromethyl-4-(E-((5-hydroxypent-1-ylamino)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-carbomethoxy-4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Biphenyl)[2-chloro-4-(E-((morpholin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (3,4-Dimethylphenyl)[2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Bromophenyl)[2-trifluoromethyl-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (5-Indolyl)[2-chloro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (5-Benzodioxolyl)[2-chloro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((2-carbomethoxypiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2,3-Dimethoxyphenyl)-[2-chloro-4(E-[(morpholin-1-yl)carbonyl]ethenyl)phenyl]sulfide;    (2-Fluorophenyl)[2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Bromophenyl)[2-trifluoromethyl-4-(E-((4-(tert-butoxycarbonyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-(Pyrrolidin-1-yl)phenyl)[2-trifluoromethyl-4-(E-((4-(tert-butoxycarbonyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (3-Carboxamidophenyl)[2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (3-(Hydroxymethyl)phenyl)[2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    Phenyl[2-trifluoromethyl-4-(E-((4-(tert-butoxycarbonyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-trifluoromethyl-4-(E-((2-carbomethoxy-4-(tert-butoxycarbonyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-(pyridine-4-methylaminocarbonyl)-4-tert-butoxycarbonylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Ethoxyphenyl)-[2-chloro-4(E-[(morpholin-1-yl)carbonyl]ethenyl)phenyl]sulfide;    (2-Methoxyphenyl)[2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-(Azetidin-1-yl)phenyl)[2-trifluoromethyl-4-(E-((4-(tert-butoxycarbonyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-(Piperidin-1-yl)phenyl)[2-trifluoromethyl-4-(E-((4-(tert-butoxycarbonyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (3-Chloro-2-formylphenyl)[2-chloro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Trifluoromethylphenyl)[2-trifluoromethyl-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (3-Bromophenyl)[2-trifluoromethyl-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (3,5-Dimethylphenyl)[2-trifluoromethyl-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-dimethylaminocarbonyl-4-(pyridine-4-carbonyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-dimethylaminocarbonyl-4-carbomethoxypiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-dimethylaminocarbonyl-4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-(1-morpholinocarbonyl)-4-tert-butoxycarbonylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-(pyridine-4-methylaminocarbonyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-(((3-dimethylaminocarbonyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-(benzylaminocarbonyl)-4-tert-butoxycarbonylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-(dimethylaminocarbonyl)-4-tert-butoxycarbonylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Bromophenyl)[2-chloro-4-(E-((3-(5S-hydroxymethyl-pyrrolidin-2-on-1-yl)prop-1-ylamino)carbonyl)ethenyl)phenyl]sulfide;    (2-Bromophenyl)[2-chloro-4-(E-((3-(pyrrolidin-2-on-1-yl)prop-1-ylamino)carbonyl)ethenyl)phenyl]sulfide;    (2-Bromophenyl)[2-chloro-4-(E-(N-methyl-N-(3-(pyrrolidin-2-on-1-yl)prop-1-yl)amino)carbonyl)ethenyl)phenyl]sulfide;    (2-[2-Methoxy]ethoxyphenyl)-[2-chloro-4(E-[(morpholin-1-yl)carbonyl]ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-(morpholinocarbonyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((4-tert-butoxycarbonylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((4-methoxycarbonylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-(4-(pyridine-4-carbonyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-(pyridine-3-methylaminocarbonyl)-4-tert-butoxycarbonylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-(pyridine-2-methylaminocarbonyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-(pyridine-3-methylaminocarbonyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (4-Hydroxyphenyl)[2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (3,5-Dichlorophenyl)[2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Bromophenyl)[2-chloro-4-(E-((3-(5S-acetoxymethyl-pyrrolidin-2-on-1-yl)prop-1-ylamino)carbonyl)ethenyl)phenyl]sulfide;    (2-Bromophenyl)[2-chloro-4-(E-((3-(5S-methoxymethyl-pyrrolidin-2-on-1-yl)prop-1-ylamino)carbonyl)ethenyl)phenyl]sulfide;    (2-Bromophenyl)[2-chloro-4-(E-((3-(4R-hydroxymethyl-pyrrolidin-2-on-1-yl)prop-1-ylamino)carbonyl)ethenyl)phenyl]sulfide;    Phenyl[2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Dimethylaminophenyl)[2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (3-((2-Hydroxyethyl)aminocarbonyl)phenyl)[2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (3-((3-(1-Imidazolyl)propyl)aminocarbonyl)phenyl)[2-nitro-4-(E-((4-acetylpiperazin 1-yl)carbonyl)ethenyl)phenyl]sulfide;    (3-((2-(1-Morpholinyl)ethyl)aminocarbonyl)phenyl)[2-nitro-4-(E-((4-acetylpiperazin 1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-hydroxymethyl-4-tert-butoxycarbonylpiperazin 1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((4-formylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((2-hydroxymethyl-4-tert-butoxycarbonylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Ethoxyphenyl)-[2-chloro-4(E-[(3-ethoxycarbonylpiperidin-1-yl)carbonyl]ethenyl)phenyl]sulfide;    (3-Aminophenyl)[2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (4-Aminophenyl)[2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2,4-Dimethylphenyl)[2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2,5-Dimethylphenyl)[2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (4-Methoxyphenyl)[2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (3-Chlorophenyl)[2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Chloro, 4,5-diaminophenyl)[2-chloro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (3,4-Diaminophenyl)[2-chloro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]   (6-Chlorobenzimidazol-2-on-5-yl)[2-chloro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (1-Methylindol-7-yl)[2-chloro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Hydroxy, 4-aminophenyl)[2-chloro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((4-methylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((4-(pyridine-2-carbonyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((4-(pyridine-3-carbonyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((2-carbomethoxy-4-methoxycarbonylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((2-carboxy-4-methoxycarbonylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-carbomethoxy-4-methylpiperazin-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-[(3-carboxypiperidin-1-yl)carbonyl]ethenyl)phenyl]sulfide;    (2-Ethoxyphenyl)-[2-chloro-4(E-[(2-ethoxycarbonylpiperidin-1-yl)carbonyl]ethenyl)phenyl]sulfide;    (2-Ethoxyphenyl)[2-trifluoromethyl-4-(E-((1-(tert-butoxycarbonyl)-4-hydroxypyrrolidin-3-ylamino)carbonyl)ethenyl)phenyl]sulfide;    (2-Ethoxyphenyl)-[2-chloro-4(E-[(2-carboxypiperidin-1-yl)carbonyl]ethenyl)phenyl]sulfide;    (2-Ethoxyphenyl)[2-trifluoromethyl-4-(E-(((pyrrol-3-in-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Ethoxyphenyl)[2-trifluoromethyl-4-(E-((3-(pyrrolidin-2-on-1-yl)prop-1-ylamino)carbonyl)ethenyl)phenyl]sulfide;    (2-Ethoxyphenyl)[2-trifluoromethyl-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Ethoxyphenyl)[2-trifluoromethyl-4-(E-((4-(ethoxycarbonyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Ethoxyphenyl)[2-trifluoromethyl-4-(E-((4-(2-furylcarbonyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Ethoxyphenyl)-[2-chloro-4(E-[(3-ethoxycarbonylpiperidin-1-yl)carbonyl]ethenyl)phenyl]sulfide;    (2-Ethoxyphenyl)-[2-chloro-4(E-[(4-carboxypiperidin-1-yl)carbonyl]ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-chloro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((4-ethoxycarbonylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((4-isopropoxycarbonylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((4-isobutoxycarbonylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((4-((1-propen-2-oxy)carbonyl)piperazin 1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((4-propionylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((4-carboxamidopiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((4-methylaminocarbonylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((4-(pyrimidin-2-yl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((4-hydroxyacetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((4-(pyrazine-2-carbonyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-trifluoromethyl-4-(E-(((2-carboxypyrrol-3-in-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-hydroxymethyl-4-methylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-trifluoromethyl-4-(E-(((2-carboxypyrrol-3-in-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-trifluoromethyl-4-(E-(((2-hydroxymethylpyrrolidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-methylaminocarbonyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-(((3-cyclopropylaminocarbonyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-carboxamidopiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-carbomethoxy-4-oxopiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3,5-dimethylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (1-Ethylindol-7-yl)[2-chloro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (3-[2-Methoxy]ethoxyphenyl)-[2-chloro-4(E-[(morpholin-1-yl)carbonyl]ethenyl)phenyl]sulfide;    (2-Bromophenyl)[2-chloro-4-(E-((4,4′-S-dioxythiomorpholin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Bromophenyl)[2-chloro-4-(E-(N-carbomethoxymethyl-N-(3-(pyrrolidin-2-on-1-yl)prop-1-yl)amino)carbonyl)ethenyl)phenyl]sulfide;    (2-Bromophenyl)[2-chloro-4-(E-((4-S-oxythiomorpholin-1-yl)-2-pyrrolidinone)carbonyl)ethenyl)phenyl]sulfide;    (2-Methoxy-5-chlorophenyl)[2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-acetoxymethyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3,5-dimethyl-4acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (1-Methylindol-5-yl)[2-chloro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-nitro-4-(E-((3-(pyrrolidin-2-on-1-yl)prop-1-ylamino)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-nitro-4-(E-((3-carboethoxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-nitro-4-(E-((4-carboethoxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Ethoxyphenyl)[2-trifluoromethyl-4-(Z-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Ethoxyphenyl)[2-trifluoromethyl-4-(E-((6-methylpyrid-2-ylamino)carbonyl)ethenyl)phenyl]sulfide;    (2-Methyl-3-chlorophenyl)[2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-nitro-4-(E-((3-carboxamidopiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-nitro-4-(E-((2-carboethoxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-nitro-4-(E-((4-carboxamidopiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-nitro-4-(E-((4-tert-butoxycarbonylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((syn-3,5-dimethylmorpholin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((anti-3,5-dimethylmorpholin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-carboethoxypiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-isopropoxycarbonylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-(dimethylaminocarbonyl)-4-methylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-carbomethoxy-4-hydroxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-hydroxymethyl-4-hydroxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Ethoxyphenyl)[2-trifluoromethyl-4-(E-((2-carbomethoxy-4-(methoxycarbonyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Ethoxyphenyl)[2-trifluoromethyl-4-(E-((2-carbomethoxy-4-methyl piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Ethoxyphenyl)[2-trifluoromethyl-4-(E-((2-carboxy-4-(methoxycarbonyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Indol-6-yl)[2-chloro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (1-Ethyl, 3-(dimethylaminomethyl)indol-7-yl)[2-chloro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (5-Ethoxybenzodioxan-6-yl)[2-chloro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Ethyl-4-bromophenyl)[2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-nitro-4-(E-((2-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-nitro-4-(E-((4-carboxymethylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (3-Morpholinophenyl)[2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (5-Ethoxybenzodioxan-8-yl)[2-chloro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (5-Chloro-8-ethoxyquinolin-7-yl)[2-chloro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-carboethoxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-(((3-ethanesulfonylaminocarbonyl)piperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-(((3-(4-methylpiperazine)sulfonylaminocarbonyl)piperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-(((3-p-toluenesulfonylaminocarbonyl)piperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-methyl-4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Hydroxyphenyl)-[2-chloro-4(E-[(morpholin-1-yl)carbonyl]ethenyl)phenyl]sulfide    (1-(Carboxymethyl)indol-5-yl)[2-chloro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-trifluoromethyl-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-(1-pyrrolidin-2-onyl)prop-1-ylamino)carbonyl)ethenyl)phenyl]sulfide;    (3-(2-Morpholinoethylamino)phenyl)[2-trifluoromethyl-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Pyrrolidin-1-ylphenyl)[2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (3-Bromophenyl)[2-nitro-4-(E-((3-carboethoxypyrrolidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (3-Bromophenyl)[2-nitro-4-(E-((4-carboethoxypyrrolidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-(Hydroxymethyl)-benzodioxan-6-yl)[2-chloro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-trifluoromethyl-4-(E-((3-(pyrrolidin-2-on-1-yl)prop-1-ylamino)carbonyl)ethenyl)phenyl]sulfide;    (3-(Dimethylaminomethyl)indol-5-yl)[2-chloro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((2-carboethoxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((2-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((4-carboethoxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((4-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-(((4-p-toluenesulfonylaminocarbonyl)piperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-carboxy-4-hydroxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-trifluoromethyl-4-(E-((3-carboethoxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-trifluoromethyl-4-(E-((2-carboethoxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-nitro-4-(E-((4-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-trifluoromethyl-4-(E-((3-carboxypyrrolidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-trifluoromethyl-4-(E-((4-carboethoxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-trifluoromethyl-4-(E-((2-carbomethoxy-4-tert-butoxycarbonylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-trifluoromethyl-4-(E-((2-carbomethoxy-4-methoxycarbonylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-trifluoromethyl-4-(E-((2-carbomethoxypiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Methyl-3-(carboethoxymethyl)indol-5-yl)[2-trifluoromethyl-4-(E-((morpholin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (1-(2-Methoxyethyl)indol-5-yl)[2-chloro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-acetoxymethyl-4-hydroxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-(dimethylaminocarbonyl)-4-hydroxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-cyanomorpholin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-carboethoxymorpholin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-(tetrazol-5-yl)morpholin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-trifluoromethyl-4-(E-((4-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-trifluoromethyl-4-(E-((2-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-trifluoromethyl-4-(E-((4-carbomethoxypiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-trifluoromethyl-4-(E-((3-aza-6,9-diooxaspiro[5.4]decan-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-trifluoro-4-(E-((4-(benzimidazolon-1-yl)piperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-trifluoromethyl-4-(E-((4-(methylaminocarbonyl)piperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-trifluoromethyl-4-(E-((3-carbomethoxy-4-methoxycarbonylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-carboxymorpholin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-trifluoromethyl-4-(E-((2-carboxy-4-methoxycarbonylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-trifluoromethyl-4-(E-((morpholin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-trifluoromethyl-4-(E-((4-(pyrrolidin-1-yl)piperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-aza-6,9-diooxaspiro[5.4]decan-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((2-(dimethylaminomethyl)piperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((piperidin-1-ylamino)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-trifluoromethyl-4-(E-((3-carboxy-4-methoxycarbonylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-(Dimethylaminocarbonyl)-benzodioxan-6-yl)[2-chloro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-(2-(methoxymethyl)tetrazol-5-yl)piperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide    (2-Isopropylphenyl)[2-nitro-4-(E-((3-(1-(methoxymethyl)tetrazol-5-yl)piperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (1-Methylindol-5-yl)[2-chloro-4-(E-((3-(1-pyrrolidin-2-onyl)propylamino)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-(tetrazol-5-yl)piperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (1-Methylindol-5-yl)[2-chloro-4-(E-((3-carboethoxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide    (1-Methylindol-5-yl)[2-chloro-4-(E-((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-(E-((3-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((2-(1-methylpyrrolidin-2-yl)ethylamino)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((4-(pyrrolidin-1-yl)piperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((4-sulfopiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-hydroxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-trifluoromethyl-4-(E-((3-((ethanesulfonylamino)carbonyl)piperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-trifluoromethyl-4-(E-((3-((p-toluenesulfonylamino)carbonyl)piperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-trifluoromethyl-4-(E-((4-((ethanesulfonylamino)carbonyl)piperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-trifluoromethyl-4-(E-((2(tetrazol-5-yl)morpholin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((2-butyl, 5-(tetrazol-5-yl)morpholin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-(and 3-)(Hydroxymethyl)-benzodioxan-6-yl)[2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-(and 3-)(Hydroxymethyl)-benzodioxan-6-yl)[2-nitro-4-(E-((3-(pyrrolidin-2-on-1-yl)prop-1-ylamino)carbonyl)ethenyl)phenyl]sulfide;    (2-(and 3-)(Hydroxymethyl)-benzodioxan-6-yl)[2-trifluoromethyl-4-(E-((3-(pyrrolidin-2-on-1-yl)prop-1-ylamino)carbonyl)ethenyl)phenyl]sulfide;    (3-Hydroxymethyl)-benzodioxan-6-yl)[2-nitro-4-(E-((3-(pyrrolidin-2-on-1-yl)prop-1-ylamino)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-chloro-4-(E-((3-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]   (2-(and 3-)(Aminomethyl)-benzodioxan-6-yl)[2-trifluoromethyl-4-(E-((3-(pyrrolidin-2-on-1-yl)prop-1-ylamino)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-(methylaminocarbonyl)morpholin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-(hydroxymethyl)morpholin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-(acetoxymethyl)morpholin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-(aminomethyl)morpholin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-(acetamidomethyl)morpholin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-chloro-4-(E-((3-(pyrrolidin-2-on-1-yl)prop-1-ylamino)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-chloro-4-(E-((3-carboethoxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-chloro-4-(E-((2-carboethoxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide    (2-Methoxyphenyl)-[2,3-dichloro-4(E-[(morpholin-1-yl)carbonyl]ethenyl)phenyl]sulfide;    (2-Methoxyphenyl)-[2,3-dimethyl-4(E-[(morpholin-1-yl)carbonyl]ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((indol-5-ylamino)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-chloro-4-(E-((3-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-chloro-4-(E-((3-(tetrazol-5-yl)piperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-chloro-4-(E-((4-(tert-butoxycarbonyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-chloro-4-(E-((2-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-chloro-4-(E-((3-(tetrazol-5-yl)morpholin-1-yl)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-carboxypiperidin-1-yl)carbonyl]ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-chloro-4-(E-((4-(tetrazol-5-yl)piperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Methoxyphenyl)-[3-chloro-4(E-[(morpholin-1-yl)carbonyl]ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((4-oxopiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-trifluoromethyl-4-(E-((3-R-carboethoxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-trifluoromethyl-4-(E-((3-R-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2,3-dichloro-4-(E-((3-(pyrrolidin-2-on-1-yl)prop-1-ylamino)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2,3-dichloro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (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-dichloro-4-(E-((3-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2,3-dichloro-4-(E-((4-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2,3-dichloro-4-(E-((3-(1-pyrrolidin-2-onyl)propylamino)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2,3-dichloro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2,3-dichloro-4-(E-((3-carboethoxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2,3-dichloro-4-(E-((4-carboethoxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2,3-dichloro-4-(E-((3-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2,3-dichloro-4-(E-((4-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (1-Methylindol-5-yl)[2,3-dichloro-4-(E-((3-carboethoxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (1-Methylindol-5-yl)[2,3-dichloro-4-(E-((3-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (1-Methylindol-5-yl)[2,3-dichloro-4-(E-((4-carboethoxypiperidin-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-dichloro-4(E-[(morpholin-1-yl)carbonyl]ethenyl)phenyl]sulfide;    (2-Ethoxyphenyl)-[2,3-dichloro-4(E-[(3-carboxypiperidin-1-yl)carbonyl]ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-carboethoxypyrrolidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-carboxypyrrolidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2,3-difluoro-4-(E-((3-carboethoxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2,3-difluoro-4-(E-((3-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2,3-difluoro-4-(E-((4-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-trifluoromethyl-4-(E-((3-ethoxycarbonylpyrrolidin-1-yl)carbonyl)ethenyl)phenyl]sulfide    (Benzodioxan-6-yl)[2-trifluoromethyl-4-(E-((3-carboxypyrrolidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Methoxyphenyl)[2-chloro-3-trifluoromethyl-4-(E-((4-carboethoxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Methoxyphenyl)[2-chloro-3-trifluoromethyl-4-(E-((4-carboethoxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Methoxyphenyl)[2-chloro-3-trifluoromethyl-4-(E-((morpholin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[4-(E-((4-carboxypiperidin-1-yl)carbonyl)ethenyl)naphthyl]sulfide;    (2-Methoxyphenyl)[2,3-dichloro-4-(E-((4-(spiro-hydantoin-5-yl)-piperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide; 
 (2-Methoxyphenyl)[2,3-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-Isopropylphenyl)[2,3-dichloro-4-(E-((4-(2-(2-hydroxyethoxy)ethyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6yl)[2,3-bis(trifluoromethyl)-4-(E-((4-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Methoxyphenyl)[2,3-dichloro-4-(E-((4-(carboxymethylamino)carbonyl-piperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Methoxyphenyl)[2,3-bis(trifluoromethyl)-4-(E-((4-carboxymethylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Methoxyphenyl)[2,3-bis(trifluoromethyl)-4-(E-((4-N-(2-hydroxyethyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (1-Methylindol-5-yl)[2,3-dichloro-4-(E-((4-(carbo-2,3-dihydroxypropylamino)piperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (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;    (1-Methylindol-5-yl)[2,3-dichloro-4-(E-((4-(carboxymethylamino)carbonyl-piperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (1-Methylindol-5-yl)[2,3-dichloro-4-(E-((4-sulfopiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (1-Methylindol-5-yl)[2,3-dichloro-4-(E-(4-methylhomopiperazin-1-ylcarbonyl)ethenyl)phenyl]sulfide;    (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)[2,3-dichloro-4-(E-(4-(carbo-3-sulfopropylamino)piperadin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Methoxyphenyl)[2,3-dichloro-4-(E-(4-acetylamino-4-carboxypiperidin-1-ylcarbonyl)ethenyl)phenyl]sulfide;    (2-Methoxyphenyl)[2,3-bis(trifluoromethyl)-4-(E-((4-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Methoxyphenyl)5-[8-(E-((4-(aminocarbonyl)piperidin-1-yl)carbonyl)ethenyl)quinolinyl]sulfide;    (2-Methoxyphenyl)[2-trifluoromethyl-4-(E-((4-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (1-Methylindol-5-yl)[2,3-dichloro-4-(E/Z-((1S,4S)-2,5-diazabycyclo(2,2,1)heptan-2-ylcarbonyl)ethenyl)-2,3-dichlorophenyl]sulfide;    (1-Methylindol-5-yl)[2,3-dichloro-4-(E-(4-hydroxy-3-carboxypiperadin-1-ylcarbonyl)ethenyl)phenyl]sulfide;    (1-Methylindol-5-yl)[2,3-dichloro-4-(E-(S-oxothiomorpholin-1-ylcarbonyl)ethenyl)phenyl]sulfide;    (2-Methoxyphenyl)[2,3-dichloro-4-(E-((4-sulfophenylamino)carbonyl)ethenyl)phenyl]sulfide;    (2-Methoxyphenyl)[2,3-dichloro-4-(E-((4-carboxyphenylamino)carbonyl)ethenyl)phenyl]sulfide;    [3-(4-Morpholino)phenyl][2,3-dichloro-4-(E-[(4-carboxypiperidin-1-yl)carbonyl]ethenyl)phenyl]sulfide;    [3-(4-Morpholino)phenyl][2,3-dichloro-4-(E-((4-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Methoxyphenyl)[2,3-bis(trifluoromethyl)-4-(E-((4-phenylcarboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Methoxyphenyl)[2,3-dichloro-4-(E-(((4-hydroxylaminocarbonyl)piperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Methoxyphenyl)[2,3-dichloro-4-(E-((N-carboxymethyl-N-phenylamino)carbonyl)ethenyl)phenyl]sulfide;    (2-Methoxyphenyl)[3-chloro-6-hydroxy-4-(E-((3-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Methoxyphenyl)[2,3-dichloro-4-(E-(4-((1-(2-phenyl-1-carboxyethyl)amino)carbonyl)piperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Methoxyphenyl)[2,3-dichloro-4-(E-(4-((1-(2-hydroxy-1-carboxyethyl)amino)carbonyl)piperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (3-(1-(3-Carboxypiperidinyl)phenyl)[2,3-dichloro-4-(E-((1,2,5,6-tetrahydropyridin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (3-(4-Pyrrolidin-1-yl)piperidin-1-yl)phenyl)[2,3-dichloro-4-(E-(((3-(2-pyrrolidinon-1-yl)propylamino)carbonyl)ethenyl)phenyl]sulfide;    [3-(4-(Spiro-2,2-dioxolanyl)piperidin-1-yl)phenyl][2,3-dichloro-4-(E-((4-morpholinyl)carbonyl)ethenyl)phenyl]sulfide;    [3-(3-Carboxylpiperidin-1-yl)phenyl][2,3-dichloro-4-(E-[(4-carboxypiperidin-1-yl)carbonyl]ethenyl)phenyl]sulfide;    (2-(2-Carboxy)ethenyl)phenyl)[2,3-dichloro-4-(E-((4-morpholinyl)carbonyl)ethenyl)phenyl]sulfide;    [3-(4-Carboxylpiperidin-1-yl)phenyl][2,3-dichloro-4-(E-[(1,2,3,6-tetrahydropyridine)-1-yl)carbonyl]ethenyl)phenyl]sulfide;    [3-(4-Carboxylpiperidinyl)phenyl][2,3-dichloro-4-(E-[(4-morpholinyl)carbonyl]ethenyl)phenyl]sulfide;    [2-(4-Acetylpiperazin-1-yl)phenyl][2,3-dichloro-4-(E-[(4-carboxypiperidin-1-yl)carbonyl]ethenyl)phenyl]sulfide;    3-(3-Carboxypiperidin-1-yl)phenyl][2,3-dichloro-4-(E-[(4-morpholinyl)carbonyl]ethenyl)phenyl]sulfide;    [3-(4-Carboxypiperidin-1-yl)phenyl][2,3-dichloro-4-(E-[(4-(dimethylaminosulfamoyl)piperazin-1-yl)carbonyl]ethenyl)phenyl]sulfide;    (2-Methoxyphenyl)[2,3-bis(trifluoromethyl)-4-(E-((3-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Methoxyphenyl)[2,3-bis(trifluoromethyl)-4-(E-((2-carboxypyrrolidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    [3-(4-Carboxypiperidin-1-yl)phenyl][2,3-dichloro-4-(E-((4-((trifluoromethylsulfonyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Methoxyphenyl)[2,3-dichloro-4-(E-(piperidin-1-ylcarbonyl)ethenyl)phenyl]sulfide;    (2-Hydroxyphenyl)[2,3-dichloro-4-(E-((4-morpholino)carbonyl)ethenyl)phenyl]sulfide;    (2-Methoxyphenyl)[2,3-dichloro-4-(E-((((4-carboxyphenyl)methyl)amino)carbonyl)ethenyl)phenyl]sulfide;    (2-Methoxyphenyl)[2,3-dichloro-4-(E-(((4-pyrrolidin-1-yl)piperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Hydroxyphenyl)[2,3-dichloro-4-(E-((4-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    [3-(4-Carboxypiperidin-1-yl)phenyl][2,3-dichloro-4-(E-((4-((methylsulfonyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Aminophenyl)[2,3-dichloro-4-(E-((4-morpholinyl)carbonyl)ethenyl)phenyl]sulfide;    (3-(4-carboxypiperidin-1-yl)phenyl)[2,3-dichloro-4-(E-((S-oxothiomorpholin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    [3-(4-Carboxypiperidin-1-yl)phenyl][2,3-dichloro-4-(E-((4-hydroxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Glycoxyphenyl)[2,3-dichloro-4-(E-((4-morpholino)carbonyl)ethenyl)phenyl]sulfide;    (2-(4-Butyroxy)phenyl)[2,3-dichloro-4-(E-((4-morpholino)carbonyl)ethenyl)phenyl]sulfide;    [3-(4-Carboxypiperidin-1-yl)phenyl][2,3-dichloro-4-(E-((4-hydroxyethylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    [3-(4-Carboxypiperidin-1-yl)phenyl][2,3-dichloro-4-(E-((4-furoylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    [3-(4-Carboxypiperidin-1-yl)phenyl][2,3-dichloro-4-(E-((pyrrolidin 1-yl)carbonyl)ethenyl)phenyl]sulfide;    [3-(4-Carboxypiperidin-1-yl)phenyl][2,3-dichloro-4-(E-((diethylaminocarbonyl)ethenyl)phenyl]sulfide;    [3-(4-Carboxypiperidin-1-yl)phenyl][2,3-dichloro-4-(E-((4-ethylpiperazin-yl)carbonyl)ethenyl)phenyl]sulfide;    [3-(4-Carboxypiperidin-1-yl)phenyl][2,3-dichloro-4-(E-((4-(aminocarbonyl)piperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    [3-(4-Carboxypiperidin-1-yl)phenyl][2,3-dichloro-4-(E-((4-(2-(ethoxyethyl)piperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    [3-((4-Carboxymethyl)piperazin-1-yl)phenyl][(2,3-dichloro-4-(E-(4-morpholinyl)carbonyl)ethenyl)phenyl]sulfide;    [3-(4-Carboxypiperidin-1-yl)phenyl][2,3-bis(trifluoromethyl)-4-(E-((4-morpholino)carbonyl)ethenyl)phenyl]sulfide;    (3-Hydroxyphenyl) [2,3-dichloro-4-(E-((4-morpholino)carbonyl)ethenyl)phenyl]sulfide;    [3-(4-Butyroxy)phenyl][2,3-dichloro-4-(E-((4-morpholino)carbonyl)ethenyl)phenyl]sulfide;    (2-Hydroxyphenyl)[2,3-bis(trifluoromethyl)-4-(E-((4-morpholino)carbonyl)ethenyl)phenyl]sulfide;    (3-Hydroxyphenyl)[2,3-bis(trifluoromethyl)-4-(E-((4-morpholino)carbonyl)ethenyl)phenyl]sulfide;    [3-(4-Carboxypiperidin-1-yl)phenyl][2,3-ditrifluoromethyl-4-(E-((4-hydroxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    [3-(4-Carboxypiperidin-1-yl)phenyl][2,3-ditrifluoromethyl-4-(E-((1,2,5,6-tetrahydropyridin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    [2-((4-Carboxy)butyloxy)phenyl][2,3-dichloro-4-(E-((4-morpholino)carbonyl)ethenyl)phenyl]sulfide;    (2-Glycoxyphenyl)[2,3-bis(trifluoromethyl)-4-(E-((4-morpholino)carbonyl)ethenyl)phenyl]sulfide;    (2-(4-Butyroxy)phenyl)[2,3-bis(trifluoromethyl)-4-(E-((4-morpholino)carbonyl)ethenyl)phenyl]sulfide;    [3-(4-Carboxypiperidin-1-yl)phenyl][2,3-ditrifluoromethyl-4-(E-((bis-(2-ethoxyethyl)amino)carbonyl)ethenyl)phenyl]sulfide;    [3-(4-Carboxypiperidin-1-yl)phenyl][2,3-bis-(trifluoromethyl)-4-(E-((bis-(2-hydroxypropyl)amino)carbonyl)ethenyl)phenyl]sulfide;    [3-(4-Carboxypiperidin-1-yl)phenyl][2,3-bis-(trifluoromethyl)-4-(E-((piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (3-(4-Butyroxy)phenyl)[2,3-bis(trifluoromethyl)-4-(E-((4-morpholino)carbonyl)ethenyl)phenyl]sulfide;    [2-(3-Carboxypiperidin-1-yl)phenyl][2,3-dichloro-4-(E-((3-(2-pyrrolidinon-1-yl)propylaminocarbonyl)ethenyl)phenyl]sulfide;    [2-(3-Carboxypiperidin-1-yl)phenyl][2,3-bis(trifluoromethyl)-4-(E-((3-(2-pyrrolidinon 1-yl)propylaminocarbonyl)ethenyl)phenyl]sulfide;    [2-(3-Carboxypiperidin-1-yl)phenyl][2,3-dichloro-4-(E-((4-(2-hydroxyethyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    [2-(3-Carboxypiperidin-1-yl)phenyl][2,3-bis(trifluoromethyl)-4-(E-((1,2,5,6-tetrahydropyridin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    [2-(3-Carboxypiperidin-1-yl)phenyl][2,3-bis(trifluoromethyl)-4-(E-((4-(2-hydroxyethyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    [2-(3-Carboxypiperidin-1-yl)phenyl][2,3-bis(trifluoromethyl)-4-(E-((4-(2-(hydroxyethoxy)ethyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; and    (3-(3-Propioxy)phenyl)[2,3-dichloro-4-(E-((4-morpholino)carbonyl)ethenyl)phenyl]sulfide.    
   
   
       13 . A pharmaceutical composition according to  claim 1  comprising a compound selected from the group consisting of: 
 (2-Formylphenyl)[2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Ethoxyphenyl)-[2-chloro-4(E-[(morpholin-1-yl)carbonyl]ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-dimethylaminocarbonyl-4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((4-methoxycarbonylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Ethoxyphenyl)[2-trifluoromethyl-4-(E-((2-carboxy-4-(methoxycarbonyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Ethyl-4-bromophenyl)[2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (3-Morpholinophenyl)[2-nitro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-carboethoxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2-nitro-4-(E-((3-(1-pyrrolidin-2-onyl)prop-1-ylamino)carbonyl)ethenyl)phenyl]sulfide;    (2-(Hydroxymethyl)-benzodioxan-6-yl)[2-chloro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-trifluoromethyl-4-(E-((3-carboxypyrrolidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-trifluoromethyl-4-(E-((4-carboethoxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-trifluoromethyl-4-(E-((2-carbomethoxy-4-methoxycarbonylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-trifluoromethyl-4-(E-((2-carbomethoxypiperazin-1-yl)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-carboxypiperidin-1-yl)carbonyl]ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2-trifluoromethyl-4-(E-((3-R-carboethoxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2,3-dichloro-4-(E-((3-(pyrrolidin-2-on-1-yl)prop-1-ylamino)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2,3-dichloro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (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-dichloro-4-(E-((3-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (Benzodioxan-6-yl)[2,3-dichloro-4-(E-((4-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2,3-dichloro-4-(E-((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2,3-dichloro-4-(E-((3-carboethoxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2,3-dichloro-4-(E-((3-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Isopropylphenyl)[2,3-dichloro-4-(E-((4-carboxypiperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Methoxyphenyl)[2,3-dichloro-4-(E-((4-(carboxymethylamino)carbonyl-piperidin-1-yl)carbonyl)ethenyl)phenyl]sulfide;    (2-Methoxyphenyl)[2,3-bis(trifluoromethyl)-4-(E-((4-carboxymethylpiperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide; and    (2-Methoxyphenyl)[2,3-bis(trifluoromethyl)-4-(E-((4-N-(2-hydroxyethyl)piperazin-1-yl)carbonyl)ethenyl)phenyl]sulfide.    
   
   
       14 . A pharmaceutical composition according to  claim 1  wherein Ar is selected from the group consisting of methoxyphenyl and isopropylphenyl.  
   
   
       15 . A pharmaceutical composition according to  claim 1  wherein Ar is benzodioxan or substituted benzodioxan.  
   
   
       16 . A pharmaceutical composition according to  claim 1  wherein R 3  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-4-one, and quinoline.  
   
   
       17 . A pharmaceutical composition according to  claim 1  wherein R 10  and R 11  are independently selected from hydrogen, alkyl, cycloalkyl, alkoxycarbonylalkyl, hydroxyalkyl, and heterocyclylalkyl.  
   
   
       18 . A pharmaceutical composition according to  claim 1  wherein NR 10 R 11  is heterocyclyl or substituted heterocyclyl.  
   
   
       19 . (canceled)  
   
   
       20 . A method of inhibiting inflammation comprising the administration of a pharmaceutical composition of  claim 1  to a mammal in need of treatment.  
   
   
       21 . A method of inhibiting inflammation comprising the administration of a pharmaceutical composition of  claim 12  to a mammal in need of treatment.  
   
   
       22 . A method of suppressing immune response comprising the administration of a pharmaceutical composition of  claim 1  to a mammal in need of treatment.  
   
   
       23 . A method of suppressing immune response comprising the administration of a pharmaceutical composition of  claim 12  to a mammal in need of treatment.  
   
   
       24 . A compound of formula II  
     
       
         
         
             
             
         
       
     
     wherein R 1  and R 2  are independently selected from the group consisting of 
 i. hydrogen,  
 j. halogen,  
 k. alkyl,  
 l. haloalkyl,  
 m. alkoxy,  
 n. cyano,  
 o. nitro, and  
 p. carboxaldehyde.  
 
   
   
       25 . A process for preparing a compound of formula II  
     
       
         
         
             
             
         
       
     
     which comprises: 
 a) reacting a compound of formula II′ 
                     
 with lithium hydroxide, and  
 b) cleaving the resulting methyl ether.  
 
   
   
       26 . The pharmaceutical composition of  claim 1  with the proviso that when three of R 1 , R 2 , R 4 , and R 5  are hydrogen, then the remaining R 1 , R 2 , R 4 , or R 5  is not carboxyl, 5-tetrazolyl, hydroxymethyl or carboxyl derivatized in the form of a pharmaceutically acceptable ester.  
   
   
       27 . A compound of formula I  
     
       
         
         
             
             
         
       
     
     or a pharmaceutically-acceptable salt or prodrug thereof,  
     wherein R 1 , R 2 , R 3 , R 4 , and R 5  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 1  or R 3  is a “cis-cinnamide” or a “trans-cinnamide,” defined as  
                     
 wherein R 8  and R 9  are independently selected from 
 f. hydrogen, and  
 g. alkyl,  
 h. carboxy alkyl,  
 i. alkylaminocarbonyl alkyl, and  
 j. dialkylaminocarbonyl alkyl,  
 
 and R 10  and R 11  are independently selected from  
 l. hydrogen,  
 m. alkyl,  
 n. cycloalkyl,  
 o. alkoxycarbonylalkyl,  
 p. hydroxyalkyl,  
 q. substituted aryl,  
 r. heterocyclyl,  
 s. heterocyclylalkyl,  
 t. heterocyclylamino,  
 u. substituted heterocyclyl, and  
 v. substituted heterocyclylalkyl,  
 or where NR 10 R 11  is heterocyclyl or substituted heterocyclyl, where substituents are independently selected from 
 1) alkyl,  
 2) alkoxy,  
 3) alkoxyalkyl,  
 4) cycloalkyl,  
 5) aryl,  
 6) heterocyclyl,  
 7) heterocyclylcarbonyl,  
 8) heterocyclylalkylaminocarbonyl,  
 9) hydroxy,  
 10) hydroxyalkyl,  
 11) hydroxyalkoxyalkyl,  
 12) carboxy,  
 13) carboxyalkyl,  
 14) carboxycarbonyl,  
 15) carboxaldehyde,  
 16) alkoxycarbonyl,  
 17) arylalkoxycarbonyl,  
 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) alkylsulfonyl,  
 34) alkylsulfonylaminocarbonyl,  
 35) arylsulfonylaminocarbonyl, and  
 36) heterocyclylsulfonylaminocarbonyl,  
 and wherein Ar is a substituted aryl group, where substitutions are independently selected from heterocyclyl and substituted heterocyclyl.  
 
 
   
   
       28 . A compound according to  claim 27 , wherein R 1  and R 2  are each trifluoromethyl.  
   
   
       29 . A compound according to  claim 27 , wherein R 3  is a “cis-cinnamide” or a “trans-cinnamide,” and R 1  is hydrogen.  
   
   
       30 . A compound according to  claim 29 , wherein R 3  is a “trans-cinnamide.” 
   
   
       31 . A compound according to  claim 27 , wherein Ar is a phenyl group substituted with a substituted heterocyclyl.  
   
   
       32 . A compound according to  claim 31 , wherein the substituted heterocyclyl is a substituted piperazinyl.  
   
   
       33 . A compound according to  claim 32 , wherein the substituted piperazinyl is substituted with an alkanoyl.
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