Cell proliferation inhibitors

Abstract

Compounds having formula (I) inhibit cellular proliferation. Processes for the preparation of the compounds, pharmaceutical compositions containing the compounds, and methods of treatment using the compounds are disclosed.

1 . A compound having formula (I)  
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salts or prodrugs thereof, wherein 
 L 1  is selected from the group consisting of 
 (1) —S(O) 2 O—,  
 (2) —OS(O) 2 —,  
 (3) —NR 7 SO 2 —, wherein R 7  is selected from the group consisting of 
 (a) hydrogen,  
 (b) hydroxy,  
 (c) amidinyl,  
 (d) a nitrogen-protecting group,  
 (e) alkanoyl,  
 (f) alkyl,  
 (g) alkenyl,  
 (h) alkynyl,  
 (i) cycloalkyl,  
 (j) cycloalkylalkyl,  
 (k) cycloalkenyl,  
 (l) cycloalkenylalkyl,  
 (m) aryloyl,  
 (n) alkoxy,  
 wherein (e)-(n) can be optionally substituted with one, two, or three substituents independently selected from the group consisting of 
 (i) hydroxyl,  
 (ii) halo,  
 (iii) cyano,  
 (iv) azido,  
 (v) carboxy,  
 (vi) amidinyl,  
 (vii) alkyl,  
 (viii) aryl,  
 (ix) oxo,  
 (x) heteroaryl,  
 (xi) heterocycloalkyl,  
 (xii) —NR c R d , wherein R c  and R d  are independently selected from the group consisting of 
 (1′) hydrogen,  
 (2′) alkyl,  
 (3′) aryl,  
 and  
 (4′) alkoxyalkyl,  
 
 
 and  
 (xiii) -(alkylene)—NR c R d ,  
 wherein for (x) and (xi), the heteroaryl and the heterocycloalkyl can be optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of 
 (1′) alkyl,  
 and  
 (2′) a nitrogen protecting group,  
 
 
 (o) heterocycloalkyloyl, wherein the heterocycloalkyloyl can be optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of 
 (i) alkyl,  
 and  
 (ii) a nitrogen protecting group,  
 
 and  
 (p) —(CH 2 ) x NR A R B , wherein x is 0-6, and R A  and R B  are independently selected from the group consisting of 
 (i) hydrogen,  
 (ii) alkyl,  
 (iii) alkenyl,  
 (iv) alkynyl,  
 (v) cycloalkyl,  
 (vi) cycloalkylalkyl,  
 (vii) cycloalkenyl,  
 and  
 (viii) cycloalkenylalkyl,  
 
 
 (4) —SO 2 NR 7 —, wherein R 7  is defined above,  
 (5) —S(O)CR 12 R 13 —, wherein R 12  and R 13  are independently selected from the group consisting of 
 (a) hydrogen,  
 (b) alkyl,  
 (c) alkenyl,  
 and  
 (d) alkynyl,  
 
 (6) —SO 2 CR 12 R 13 —,  
 (7) —SCR 12 R 13 —,  
 (8) —CR 12 R 13 S(O)—,  
 (9) —CR 12 R 13 SO 2 —,  
 and  
 (10) —CR 12 R 13 S—,  
 wherein (1)-(10) are shown with their left ends attached to R 1  and their right ends attached to the phenyl ring;  
 R 1  is aryl or heteroaryl, wherein the aryl or the heteroaryl can be optionally substituted with 1, 2, 3, 4,or 5 substituents independently selected from the group consisting of 
 (a) oxo,  
 (b) azido,  
 (c) carboxy,  
 (d) carboxaldehyde,  
 (e) cyano,  
 (f) halo,  
 (g) hydroxy,  
 (h) nitro,  
 (i) perfluoroalkyl,  
 (j) perfluoroalkoxy,  
 (k) alkyl,  
 (l) alkenyl,  
 (m) alkynyl,  
 (n) alkanoyloxy,  
 (o) alkoxycarbonyl,  
 (p) cycloalkyl,  
 (q) cycloalkylalkyl,  
 (r) cycloalkenyl,  
 (s) cycloalkenylalkyl,  
 (t) alkanoyl,  
 (u) alkoxy,  
 (v) cycloalkoxy,  
 (w) aryloxy,  
 (x) heteroaryloxy,  
 (y) thioalkoxy  
 (z) alkylsulfinyl,  
 (aa) alkylsulfonyl,  
 (bb) —NR 8 R 9 , wherein R 8  and R 9  are independently selected from the group consisting of 
 (i) hydrogen  
 (ii) alkyl,  
 (iii) arylalkyl,  
 and  
 (iv) alkanoyl, wherein the alkanoyl can be optionally substituted with 1 or 2 substituents independently selected from the group consisting of 
 (1′) halo  
 (2′) hydroxy,  
 and  
 (3′) —NR 10 R 11  wherein R 10  and R 11  are independently hydrogen or alkyl,  
 
 
 
 and  
 (cc) —SO 2 NR 8 R 9 , wherein R 8  and R 9  are defined above;  
 R 2  and R 6  are independently selected from the group consisting of 
 (1) hydrogen,  
 (2) alkyl,  
 (3) alkoxy,  
 (4) thioalkoxy;  
 and  
 (5) hydroxy,  
 
 and  
 R 3 , R 4 , and R 5  are independently selected from the group consisting of 
 (1) alkyl,  
 (2) alkoxy,  
 (3) thioalkoxy,  
 and  
 (4) hydroxy;  
 
 all of the foregoing with the proviso that combinations wherein L 1  is —NR 7 SO 2 — and R 1  is 
 (1) unsubstituted or substituted 1H-indoly-7-yl,  
 (2) phenyl which is 2-monosubstituted with —NR 8 R 9 ,  
 (3) pyrid-3-yl which is 2-monosubstituted with —NR 8 R 9 , or  
 (4) pyrimidin-5-yl which is 4-monosubstituted with —NR 8 R 9 ,  
 are excluded therefrom.  
 
 
     
     
         2 . A compound according to  claim 1 , wherein L 1  is —SO 2 NR 7 —, and R 7  is defined above.  
     
     
         3 . A compound according to  claim 2 , wherein R 2  and R 6  are hydrogen, and R 3 , R 4 , and R 5  are methoxy.  
     
     
         4 . A compound according to  claim 3 , wherein R 1  is optionally substituted aryl.  
     
     
         5 . A compound according to  claim 4  selected from the group consisting of 
 4-methoxy-N-(3,4,5-trimethoxyphenyl)benzenesulfonamide,    3,4-dimethoxy-N-(3,4,5-trimethoxyphenyl)benzenesulfonamide,    4-trifluoromethoxy-N-(3,4,5-trimethoxyphenyl)benzenesulfonamide,    4-trifluoromethyl-N-(3,4,5-trimethoxyphenyl)benzenesulfonamide,    4-nitro-N-(3,4,5-trimethoxyphenyl)benzenesulfonamide,    4-amino-N-(3,4,5-trimethoxyphenyl)benzenesulfonamide,    4-((2-chloroacetyl)amino)-N-(3,4,5-trimethoxyphenyl)benzenesulfonamide,    2-nitro-N-(3,4,5-trimethoxyphenyl)benzenesulfonamide,    4-methoxy-3-nitro-N-(3,4,5-trimethoxyphenyl)benzenesulfonamide,    3-amino-4-methoxy-N-(3,4,5-trimethoxyphenyl)benzenesulfonamide, and    3-amino-4-methoxy-N-methyl-N-(3,4,5-trimethoxyphenyl)benzenesulfonamide.    
     
     
         6 . A compound according to  claim 3 , wherein R 1  is optionally substituted heteroaryl.  
     
     
         7 . A compound according to  claim 6 , wherein R 1  is optionally substituted 2,3-dihydro-1H-indol-5-yl.  
     
     
         8 . A compound according to  claim 7  selected from the group consisting of 
 1-formyl-N-(3,4,5-trimethoxyphenyl)indoline-5-sulfonamide,    N-(3,4,5-trimethoxyphenyl)indoline-5-sulfonamide, and    1-methyl-N-(3,4,5-trimethoxyphenyl)indoline-5-sulfonamide.    
     
     
         9 . A compound according to  claim 6 , wherein R 1  is optionally substituted 1H-indol-3-yl.  
     
     
         10 . A compound according to  claim 9  selected from the group consisting of 
 5-nitro-N-(3,4,5-trimethoxyphenyl)-1H-indole-3-sulfonamide,    1-methyl-5-nitro-N-(3,4,5-trimethoxyphenyl)-1H-indole-3-sulfonamide,    5-amino-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-3-sulfonamide, and    5-amino-N-(3,4,5-trimethoxyphenyl)-1H-indole-3-sulfonamide.    
     
     
         11 . A compound according to  claim 6 , wherein R 1  is optionally substituted 1H-indol-5-yl.  
     
     
         12 . A compound according to  claim 11  selected from the group consisting of 
 N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    N,1-dimethyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    1-ethyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    N-(2-hydroxyethyl)-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    N-(2-fluoroethyl)-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    N-ethyl-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    N-((dimethylamino)acetyl)-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    1-methyl-N-(((2S)-1-methylpyrrolidinyl)carbonyl)-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    N-((2S)-2-(dimethylamino)-3-methylbutanoyl)-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    N-((2S)-2-amino-3-methylbutanoyl)-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    1-methyl-N-((2S)-2-methylamino)propanoyl)-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    N-(( 2 S)-2-amino-2-phenylethanoyl)-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    N-((2S)-2-amino-3-phenylpropanoyl)-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    1-methyl-N-((2S)-pyrrolidinylcarbonyl)-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    N-((2S)-2,6-diaminohexanoyl)-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    N-((2S)-2-amino-3-(1H-imidazol-5-yl)propanoyl)-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    (2S)-2-amino-4-oxo-4-(3,4,5-trimethoxy((1-methyl-1H-indol-5-yl)sulfonyl)anilino)butanoic acid,    (3S)-3-amino-4-oxo-4-(3,4,5-trimethoxy((1-methyl-1H-indol-5-yl)sulfonyl)anilino)butanoic acid,    (2S)-2-amino-5-oxo-5-(3,4,5-trimethoxy((1-methyl-1H-indol-5-yl)sulfonyl)anilino)pentanoic acid,    (4S)-4-amino-5-oxo-5-(3,4,5-trimethoxy((1-methyl-1H-indol-5-yl)sulfonyl)anilino)pentanoic acid,    N-((bis(2-methoxyethyl)amino)acetyl)-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    1-methyl-N-(4-morpholinylacetyl)-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    1-methyl-N-((4-methyl-1-piperazinyl)acetyl)-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    N-(4-(aminomethyl)benzoyl)-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    N-(2-aminoacetyl)-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    N-(( 2 S)-2-aminopropanoyl]-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    N-(3-aminopropanoyl)-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide, (2S)-2-amino-N-((1S)-1-methyl-2-oxo-2-(3,4,5-trimethoxy((1-methyl-1H-indol-5-yl)sulfonyl)anilino)ethyl)propanamide, and    N-((2S)-2-amino-3-hydroxypropanoyl)-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide.    
     
     
         13 . A compound according to  claim 1 , wherein L 1  is —NR 7 SO 2 —, and R 7  is defined above.  
     
     
         14 . A compound according to  claim 13 , wherein R 2  and R 6  are hydrogen, and R 3 , R 4 , and R 5  are methoxy.  
     
     
         15 . A compound according to  claim 14  selected from the group consisting of 
 3,4,5-trimethoxy-N-(4-methoxyphenyl)benzenesulfonamide,    N-(3-hydroxy-4-methoxyphenyl)-3,4,5-trimethoxybenzenesulfonamide,    N-(1-methyl-1H-indol-5-yl)-3,4,5-trimethoxybenzenesulfonamide,    N-(4-(dimethylamino)phenyl)-3,4,5-trimethoxybenzenesulfonamide,    N-(4-fluoro-3-methoxyphenyl)-3,4,5-trimethoxybenzenesulfonamide,    3,4,5-trimethoxy-N-(4-(trifluoromethoxy)phenyl)benzenesulfonamide,    3,4,5-trimethoxy-N-(2,3,4,5,6-pentafluorophenyl)benzenesulfonamide,    N-(3-amino-4-methoxyphenyl)-3,4,5-trimethoxybenzenesulfonamide,    3,4,5-trimethoxy-N-(1-methyl-1H-indol-4-yl)benzenesulfonamide,    3,4,5-trimethoxy-N-(1-methyl-1H-indol-6-yl)benzenesulfonamide,    N-(1H-indol-5-yl)-3,4,5-trimethoxybenzenesulfonamide,    N-(1,2-dimethyl-1H-indol-5-yl)-3,4,5-trimethoxybenzenesulfonamide,    N-(3-chloro-1H-indol-5-yl)-3,4,5-trimethoxybenzenesulfonamide,    N-(1H-indazol-5-yl)-3,4,5-trimethoxybenzenesulfonamide,    3,4,5-trimethoxy-N-(1-methyl-1H-benzimidazol-6-yl) benzenesulfonamide,    3,4,5-trimethoxy-N-(1-methyl-1H-benzimidazol-5-yl)benzenesulfonamide,    3,4,5-trimethoxy-N-methyl-N-(1-methyl-1H-indol-5-yl) benzenesulfonamide,    3,4,5-trimethoxy-N-(2-(dimethylamino)ethyl)-N-(1-methyl-1H-indol-5-yl)benzenesulfonamide,    tert-butyl 2-((1-methyl-1H-indol-5-yl)((3,4,5-trimethoxyphenyl)sulfonyl)amino)ethylcarbamate,    N-(2-hydroxyethyl)-3,4,5-trimethoxy-N-(1-methyl-1H-indol-5-yl)benzenesulfonamide,    N-(2,3-dihydro-1,4-benzodioxin-6-yl)-3,4,5-trimethoxybenzenesulfonamide,    N-(2-aminoethyl)-3,4,5-trimethoxy-N-(1-methyl-1H-indol-5-yl)benzenesulfonamide,    N-acetyl-3,4,5-trimethoxy-N-(1-methyl-1H-indol-5-yl)benzenesulfonamide,    3,4,5-trimethoxy-N-(6-quinolinyl)benzenesulfonamide,    N-(2-aminoacetyl)-3,4,5-trimethoxy-N-(1-methyl-1H-indol-5-yl)benzenesulfonamide,    N-((2S)-2-aminopropanoyl]-3,4,5-trimethoxy-N-(1-methyl-1H-indol-5-yl)benzenesulfonamide,    N-(3-aminopropanoyl)-3,4,5-trimethoxy-N-(1-methyl-1H-indol-5-yl)benzenesulfonamide,    (2S)-2-amino-N-((1S)-1-methyl-2-((1-methyl-1H-indol-5-yl)((3,4,5-trimethoxyphenyl)sulfonyl)amino)-2-oxoethyl)propanamide, and    N-((2S)-2-amino-3-hydroxypropanoyl)-3,4,5-trimethoxy-N-(1-methyl-1H-indol-5-yl)benzenesulfonamide.    
     
     
         16 . A compound according to  claim 1 , wherein L 1  is —OSO 2 —.  
     
     
         17 . A compound according to  claim 16 , wherein R 2  and R 6  are hydrogen, and R 3 , R 4 , and R 5  are methoxy.  
     
     
         18 . A compound according to  claim 17  selected from the group consisting of 
 1H-indol-5-yl 3,4,5-trimethoxybenzenesulfonate,    1H-indol-5-yl 3,4,5-trimethoxybenzenesulfonate,    4-methylphenyl 3,4,5-trimethoxybenzenesulfonate,    4-methoxyphenyl 3,4,5-trimethoxybenzenesulfonate,    4-nitrophenyl-3,4,5-trimethoxybenzenesulfonate,    4-aminophenyl-3,4,5-trimethoxybenzenesulfonate,    4-dimethylaminophenyl-3,4,5-trimethoxybenzenesulfonate,    and    1-methyl-2-oxo-1,2-dihydro-4-pyridinyl 3,4,5-trimethoxybenzenesulfonate.    
     
     
         19 . A compound according to  claim 1 , wherein L 1  is —SO 2 O—.  
     
     
         20 . A compound according to  claim 19 , wherein R 2  and R 6  are hydrogen, and R 3 , R 4 , and R 5  are methoxy.  
     
     
         21 . A compound according to  claim 20  selected from the group consisting of 
 (3,4,5-trimethoxyphenyl) 4-methoxybenzenesulfonate,    3,4,5-trimethoxyphenyl) 4-methylbenzenesulfonate,    3,4,5-trimethoxyphenyl) 3-amino-4-methoxybenzenesulfonate,    (3,4,5-trimethoxyphenyl)-4-(dimethylamino)benzenesulfonate,    3,4,5-trimethoxyphenyl 1-methyl-5-indolinesulfonate,    3,4,5-trimethoxyphenyl 6-methoxy-3-pyridinesulfonate,    3,4,5-trimethoxyphenyl 3-((3-aminopropanoyl)amino)-4-methoxybenzenesulfonate,    3,4,5-trimethoxyphenyl 3-(((2R)-2-aminopropanoyl)amino)-4-methoxybenzenesulfonate,    and    3,4,5-trimethoxyphenyl 3-(((2R)-2-amino-3-methylbutanoyl)amino)-4-methoxybenzenesulfonate.    
     
     
         22 . A compound according to  claim 1 , wherein L 1  is selected from the group consisting of —SO 2 CR 12 R 13 —, —SCR 12 R 13 —, —CR 12 R 13 S(O)—, —CR 12 R 13 SO 2 —, and —CR 12  R 13 S—.  
     
     
         23 . A compound according to  claim 22  selected from the group consisting of 
 1,2,3-trimethoxy-5-((4-methoxybenzyl)sulfanyl)benzene,    1,2,3-trimethoxy-5-((4-methoxybenzyl)sulfinyl)benzene,    1,2,3-trimethoxy-5-((4-methoxybenzyl)sulfonyl)benzene,    1,2,3-trimethoxy-5-((1-(4-methoxyphenyl)-1-methylethyl)sulfonyl)benzene,    2-methoxy-5-(((3,4,5-trimethoxyphenyl)sulfanyl)methyl)aniline,    2-methoxy-5-(((3,4,5-trimethoxyphenyl)sulfinyl)methyl)aniline,    2-methoxy-5-(((3,4,5-trimethoxyphenyl)sulfonyl)methyl)aniline,    2-methoxy-5-(1-methyl-1-((3,4,5-trimethoxyphenyl)sulfonyl)ethyl)aniline,    1,2,3-trimethoxy-5-(((4-methoxyphenyl)sulfanyl)methyl)benzene,    1,2,3-trimethoxy-5-(((4-methoxyphenyl)sulfonyl)methyl)benzene,    1,2,3-trimethoxy-5-(1-((4-methoxyphenyl)sulfonyl)-1-methylethyl)benzene,    2-methoxy-5-((3,4,5-trimethoxybenzyl)sulfonyl)aniline,    2-methoxy-5-((1-methyl-1-(3,4,5-trimethoxyphenyl)ethyl)sulfonyl)aniline, and    1,2,3-trimethoxy-5-((phenylsulfonyl)methyl)benzene.    
     
     
         24 . A method of inhibiting polymerization of tubulin in a mammal in recognized need of such treatment comprising administering an effective amount of a compound of  claim 1 .  
     
     
         25 . A method of treating cancer in a mammal in recognized need of such treatment comprising administering an effective amount of a compound of  claim 1 .  
     
     
         26 . A compound selected from the group consisting of 
 4-methoxy-N-(3,4,5-trimethoxyphenyl)benzenesulfonamide,    3,4-dimethoxy-N-(3,4,5-trimethoxyphenyl)benzenesulfonamide,    4-trifluoromethoxy-N-(3,4,5-trimethoxyphenyl)benzenesulfonamide,    4-trifluoromethyl-N-(3,4,5-trimethoxyphenyl)benzenesulfonamide,    4-nitro-N-(3,4,5-trimethoxyphenyl)benzenesulfonamide,    4-amino-N-(3,4,5-trimethoxyphenyl)benzenesulfonamide,    4-((2-chloroacetyl)amino)-N-(3,4,5-trimethoxyphenyl)benzenesulfonamide,    2-nitro-N-(3,4,5-trimethoxyphenyl)benzenesulfonamide,    4-methoxy-3-nitro-N-(3,4,5-trimethoxyphenyl)benzenesulfonamide,    3-amino-4-methoxy-N-(3,4,5-trimethoxyphenyl)benzenesulfonamide,    1-formyl-N-(3,4,5-trimethoxyphenyl)indoline-5-sulfonamide,    N-(3,4,5-trimethoxyphenyl)indoline-5-sulfonamide,    5-nitro-N-(3,4,5-trimethoxyphenyl)-1H-indole-3-sulfonamide,    1-methyl-N-(3,4,5-trimethoxyphenyl)indoline-5-sulfonamide,    1-methyl-5-nitro-N-(3,4,5-trimethoxyphenyl)-1H-indole-3-sulfonamide,    5-amino-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-3-sulfonamide,    5-amino-N-(3,4,5-trimethoxyphenyl)-1H-indole-3-sulfonamide,    N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    N,1-dimethyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    3,4,5-trimethoxy-N-(4-methoxyphenyl)benzenesulfonamide,    N-(3-hydroxy-4-methoxyphenyl)-3,4,5-trimethoxybenzenesulfonamide,    N-(1-methyl-1H-indol-5-yl)-3,4,5-trimethoxybenzenesulfonamide,    N-(4-(dimethylamino)phenyl)-3,4,5-trimethoxybenzenesulfonamide,    N-(4-fluoro-3-methoxyphenyl)-3,4,5-trimethoxybenzenesulfonamide,    3,4,5-trimethoxy-N-(4-(trifluoromethoxy)phenyl)benzenesulfonamide,    3,4,5-trimethoxy-N-(2,3,4,5,6-pentafluorophenyl)benzenesulfonamide,    N-(3-amino-4-methoxyphenyl)-3,4,5-trimethoxybenzenesulfonamide,    3,4,5-trimethoxy-N-(1-methyl-1H-indol-4-yl)benzenesulfonamide,    3,4,5-trimethoxy-N-(1-methyl-1H-indol-6-yl)benzenesulfonamide,    N-(1H-indol-5-yl)-3,4,5-trimethoxybenzenesulfonamide,    N-(1,2-dimethyl-1H-indol-5-yl)-3,4,5-trimethoxybenzenesulfonamide,    N-(3-chloro-1H-indol-5-yl)-3,4,5-trimethoxybenzenesulfonamide,    N-(1H-indazol-5-yl)-3,4,5-trimethoxybenzenesulfonamide,    3,4,5-trimethoxy-N-(1-methyl-1H-benzimidazol-6-yl) benzenesulfonamide,    3,4,5-trimethoxy-N-(1-methyl-1H-benzimidazol-5-yl)benzenesulfonamide,    3,4,5-trimethoxy-N-methyl-N-(1-methyl-1H-indol-5-yl) benzenesulfonamide,    3,4,5-trimethoxy-N-(2-(dimethylamino)ethyl)-N-(1-methyl-1H-indol-5-yl)benzenesulfonamide,    1H-indol-5-yl 3,4,5-trimethoxybenzenesulfonate,    (3,4,5-trimethoxyphenyl) 4-methoxybenzenesulfonate,    3,4,5-trimethoxyphenyl) 4-methylbenzenesulfonate,    1H-indol-5-yl 3,4,5-trimethoxybenzenesulfonate,    3,4,5-trimethoxyphenyl) 3-amino-4-methoxybenzenesulfonate,    (3,4,5-trimethoxyphenyl)-4-(dimethylamino)benzenesulfonate,    4-methylphenyl 3,4,5-trimethoxybenzenesulfonate,    3,4,5-trimethoxyphenyl 1-methyl-5-indolinesulfonate, and    4-methoxyphenyl 3,4,5-trimethoxybenzenesulfonate,    tert-butyl 2-((1-methyl-1H-indol-5-yl)((3,4,5-trimethoxyphenyl)sulfonyl)amino)ethylcarbamate,    N-(2-hydroxyethyl)-3,4,5-trimethoxy-N-(1-methyl-1H-indol-5-yl)benzenesulfonamide,    N-(2,3-dihydro-1,4-benzodioxin-6-yl)-3,4,5-trimethoxybenzenesulfonamide,    N-(2-aminoethyl)-3,4,5-trimethoxy-N-(1-methyl-1H-indol-5-yl)benzenesulfonamide,    3-amino-4-methoxy-N-methyl-N-(3,4,5-trimethoxyphenyl)benzenesulfonamide,    1-ethyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    N-acetyl-3,4,5-trimethoxy-N-(1-methyl-1H-indol-5-yl)benzenesulfonamide,    3,4,5-trimethoxy-N-(6-quinolinyl)benzenesulfonamide,    N-(2-hydroxyethyl)-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    N-(2-fluoroethyl)-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    N-ethyl-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    4-nitrophenyl-3,4,5-trimethoxybenzenesulfonate,    4-aminophenyl-3,4,5-trimethoxybenzenesulfonate,    4-dimethylaminophenyl-3,4,5-trimethoxybenzenesulfonate,    3,4,5-trimethoxyphenyl 6-methoxy-3-pyridinesulfonate,    1-methyl-2-oxo-1,2-dihydro-4-pyridinyl 3,4,5-trimethoxybenzenesulfonate,    3,4,5-trimethoxyphenyl 3-((3-aminopropanoyl)amino)-4-methoxybenzenesulfonate,    3,4,5-trimethoxyphenyl 3-(((2R)-2-aminopropanoyl)amino)-4-methoxybenzenesulfonate,    3,4,5-trimethoxyphenyl 3-(((2R)-2-amino-3-methylbutanoyl)amino)-4-methoxybenzenesulfonate,    N-((dimethylamino)acetyl)-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    1-methyl-N-(((2S)-1-methylpyrrolidinyl)carbonyl)-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    N-((2S)-2-(dimethylamino)-3-methylbutanoyl)-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    N-((2S)-2-amino-3-methylbutanoyl)-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide, 1-methyl-N-((2S)-2-methylamino)propanoyl)-N-(3,4,5-trimethoxyphenyl)1H-indole-5-sulfonamide,    N-((2S)-2-amino-2-phenylethanoyl)-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    N-((2S)-2-amino-3-phenylpropanoyl)-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    1-methyl-N-((2S)-pyrrolidinylcarbonyl)-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    N-((2S)-2,6-diaminohexanoyl)-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    N-((2S)-2-amino-3-(1H-imidazol-5-yl)propanoyl)-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    (2S)-2-amino-4-oxo-4-(3,4,5-trimethoxy((1-methyl-1H-indol-5-yl)sulfonyl)anilino)butanoic acid,    (3S)-3-amino-4-oxo-4-(3,4,5-trimethoxy((1-methyl-1H-indol-5-yl)sulfonyl)anilino)butanoic acid,    (2S)-2-amino-5-oxo-5-(3,4,5-trimethoxy((1-methyl-1H-indol-5-yl)sulfonyl)anilino)pentanoic acid,    (4S)-4-amino-5-oxo-5-(3,4,5-trimethoxy((1-methyl-1H-indol-5-yl)sulfonyl)anilino)pentanoic acid,    N-((bis(2-methoxyethyl)amino)acetyl)-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    1-methyl-N-(4-morpholinylacetyl)-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    1-methyl-N-((4-methyl-1-piperazinyl)acetyl)-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    N-(4-(aminomethyl)benzoyl)-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    1,2,3-trimethoxy-5-((4-methoxybenzyl)sulfanyl)benzene,    1,2,3-trimethoxy-5-((4-methoxybenzyl)sulfinyl)benzene,    1,2,3-trimethoxy-5-((4-methoxybenzyl)sulfonyl)benzene,    1,2,3-trimethoxy-5-((1-(4-methoxyphenyl)-1-methylethyl)sulfonyl)benzene,    2-methoxy-5-(((3,4,5-trimethoxyphenyl)sulfanyl)methyl)aniline,    2-methoxy-5-(((3,4,5-trimethoxyphenyl)sulfinyl)methyl)aniline,    2-methoxy-5-(((3,4,5-trimethoxyphenyl)sulfonyl)methyl)aniline,    2-methoxy-5-(1-methyl-1-((3,4,5-trimethoxyphenyl)sulfonyl)ethyl)aniline,    1,2,3-trimethoxy-5-(((4-methoxyphenyl)sulfanyl)methyl)benzene,    1,2,3-trimethoxy-5-(((4-methoxyphenyl)sulfonyl)methyl)benzene,    1,2,3-trimethoxy-5-(1-((4-methoxyphenyl)sulfonyl)-1-methylethyl)benzene,    2-methoxy-5-((3,4,5-trimethoxybenzyl)sulfonyl)aniline,    2-methoxy-5-((1-methyl-1-(3,4,5-trimethoxyphenyl)ethyl)sulfonyl)aniline,    1,2,3-trimethoxy-5-((phenylsulfonyl)methyl)benzene,    N-(2-aminoacetyl)-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    N-(2-aminoacetyl)-3,4,5-trimethoxy-N-(1-methyl-1H-indol-5-yl)benzenesulfonamide,    N-((2S)-2-aminopropanoyl]-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    N-((2S)-2-aminopropanoyl]-3,4,5-trimethoxy-N-(1-methyl-1H-indol-5-yl)benzenesulfonamide,    N-(3-aminopropanoyl)-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    N-(3-aminopropanoyl)-3,4,5-trimethoxy-N-(1-methyl-1H-indol-5-yl)benzenesulfonamide,    (2S)-2-amino-N-((1S)-1-methyl-2-oxo-2-(3,4,5-trimethoxy((1-methyl-1H-indol-5-yl)sulfonyl)anilino)ethyl)propanamide,    (2S)-2-amino-N-((1S)-1-methyl-2-((1-methyl-1H-indol-5-yl)((3,4,5-trimethoxyphenyl)sulfonyl)amino)-2-oxoethyl)propanamide,    N-((2S)-2-amino-3-hydroxypropanoyl)-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide, and    N-((2S)-2-amino-3-hydroxypropanoyl)-3,4,5-trimethoxy-N-(1-methyl-1H-indol-5-yl)benzenesulfonamide.    
     
     
         27 . A compound selected from the group consisting of 
 4-methoxy-N-(3,4,5-trimethoxyphenyl)benzenesulfonamide,    3,4-dimethoxy-N-(3,4,5-trimethoxyphenyl)benzenesulfonamide,    4-trifluoromethoxy-N-(3,4,5-trimethoxyphenyl)benzenesulfonamide,    4-trifluoromethyl-N-(3,4,5-trimethoxyphenyl)benzenesulfonamide,    4-nitro-N-(3,4,5-trimethoxyphenyl)benzenesulfonamide,    4-amino-N-(3,4,5-trimethoxyphenyl)benzenesulfonamide,    4-((2-chloroacetyl)amino)-N-(3,4,5-trimethoxyphenyl)benzenesulfonamide,    2-nitro-N-(3,4,5-trimethoxyphenyl)benzenesulfonamide,    4-methoxy-3-nitro-N-(3,4,5-trimethoxyphenyl)benzenesulfonamide,    3-amino-4-methoxy-N-(3,4,5-trimethoxyphenyl)benzenesulfonamide,    1-formyl-N-(3,4,5-trimethoxyphenyl)indoline-5-sulfonamide,    N-(3,4,5-trimethoxyphenyl)indoline-5-sulfonamide,    5-nitro-N-(3,4,5-trimethoxyphenyl)-1H-indole-3-sulfonamide,    1-methyl-N-(3,4,5-trimethoxyphenyl)indoline-5-sulfonamide,    1-methyl-5-nitro-N-(3,4,5-trimethoxyphenyl)-1H-indole-3-sulfonamide,    5-amino-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-3-sulfonamide,    5-amino-N-(3,4,5-trimethoxyphenyl)-1H-indole-3-sulfonamide,    N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    N,1-dimethyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    3,4,5-trimethoxy-N-(4-methoxyphenyl)benzenesulfonamide,    N-(3-hydroxy-4-methoxyphenyl)-3,4,5-trimethoxybenzenesulfonamide,    N-(1-methyl-1H-indol-5-yl)-3,4,5-trimethoxybenzenesulfonamide,    N-(4-(dimethylamino)phenyl)-3,4,5-trimethoxybenzenesulfonamide,    N-(4-fluoro-3-methoxyphenyl)-3,4,5-trimethoxybenzenesulfonamide,    3,4,5-trimethoxy-N-(4-(trifluoromethoxy)phenyl)benzenesulfonamide,    3,4,5-trimethoxy-N-(2,3,4,5,6-pentafluorophenyl)benzenesulfonamide,    N-(3-amino-4-methoxyphenyl)-3,4,5-trimethoxybenzenesulfonamide,    3,4,5-trimethoxy-N-(1-methyl-1H-indol-4-yl)benzenesulfonamide,    3,4,5-trimethoxy-N-(1-methyl-1H-indol-6-yl)benzenesulfonamide,    N-(1H-indol-5-yl)-3,4,5-trimethoxybenzenesulfonamide,    N-(1,2-dimethyl-1H-indol-5-yl)-3,4,5-trimethoxybenzenesulfonamide,    N-(3-chloro-1H-indol-5-yl)-3,4,5-trimethoxybenzenesulfonamide,    N-(1H-indazol-5-yl)-3,4,5-trimethoxybenzenesulfonamide,    3,4,5-trimethoxy-N-(1-methyl-1H-benzimidazol-6-yl) benzenesulfonamide,    3,4,5-trimethoxy-N-(1-methyl-1H-benzimidazol-5-yl)benzenesulfonamide,    3,4,5-trimethoxy-N-methyl-N-(1-methyl-1H-indol-5-yl) benzenesulfonamide,    3,4,5-trimethoxy-N-(2-(dimethylamino)ethyl)-N-(1-methyl-1H-indol-5-yl)benzenesulfonamide,    1H-indol-5-yl 3,4,5-trimethoxybenzenesulfonate,    (3,4,5-trimethoxyphenyl) 4-methoxybenzenesulfonate,    3,4,5-trimethoxyphenyl) 4-methylbenzenesulfonate,    1H-indol-5-yl 3,4,5-trimethoxybenzenesulfonate,    3,4,5-trimethoxyphenyl) 3-amino-4-methoxybenzenesulfonate,    (3,4,5-trimethoxyphenyl)-4-(dimethylamino)benzenesulfonate,    4-methylphenyl 3,4,5-trimethoxybenzenesulfonate,    3,4,5-trimethoxyphenyl 1-methyl-5-indolinesulfonate, and    4-methoxyphenyl 3,4,5-trimethoxybenzenesulfonate,    tert-butyl 2-((1-methyl-1H-indol-5-yl)((3,4,5-trimethoxyphenyl)sulfonyl)amino)ethylcarbamate,    N-(2-hydroxyethyl)-3,4,5-trimethoxy-N-(1-methyl-1H-indol-5-yl)benzenesulfonamide,    N-(2,3-dihydro-1,4-benzodioxin-6-yl)-3,4,5-trimethoxybenzenesulfonamide,    N-(2-aminoethyl)-3,4,5-trimethoxy-N-(1-methyl-1H-indol-5-yl)benzenesulfonamide,    3-amino-4-methoxy-N-methyl-N-(3,4,5-trimethoxyphenyl)benzenesulfonamide,    1-ethyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    N-acetyl-3,4,5-trimethoxy-N-(1-methyl-1H-indol-5-yl)benzenesulfonamide,    3,4,5-trimethoxy-N-(6-quinolinyl)benzenesulfonamide,    N-(2-hydroxyethyl)-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    N-(2-fluoroethyl)-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    N-ethyl-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    4-nitrophenyl-3,4,5-trimethoxybenzenesulfonate,    4-aminophenyl-3,4,5-trimethoxybenzenesulfonate,    4-dimethylaminophenyl-3,4,5-trimethoxybenzenesulfonate,    3,4,5-trimethoxyphenyl 6-methoxy-3-pyridinesulfonate,    1-methyl-2-oxo-1,2-dihydro-4-pyridinyl 3,4,5-trimethoxybenzenesulfonate.    3,4,5-trimethoxyphenyl 3-((3-aminopropanoyl)amino)-4-methoxybenzenesulfonate,    3,4,5-trimethoxyphenyl 3-(((2R)-2-aminopropanoyl)amino)-4-methoxybenzenesulfonate,    3,4,5-trimethoxyphenyl 3-(((2R)-2-amino-3-methylbutanoyl)amino)-4-methoxybenzenesulfonate,    N-((dimethylamino)acetyl)-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    1-methyl-N-(((2S)-1-methylpyrrolidinyl)carbonyl)-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    N-((2S)-2-(dimethylamino)-3-methylbutanoyl)-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    N-((2S)-2-amino-3-methylbutanoyl)-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    1-methyl-N-((2S)-2-methylamino)propanoyl)-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    N-((2S)-2-amino-2-phenylethanoyl)-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    N-((2S)-2-amino-3-phenylpropanoyl)-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    1-methyl-N-((2S)-pyrrolidinylcarbonyl)-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    N-((2S)-2,6-diaminohexanoyl)-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    N-((2S)-2-amino-3-(1H-imidazol-5-yl)propanoyl)-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    (2S)-2-amino-4-oxo-4-(3,4,5-trimethoxy((1-methyl-1H-indol-5-yl)sulfonyl)anilino)butanoic acid,    (3S)-3-amino-4-oxo-4-(3,4,5-trimethoxy((1-methyl-1H-indol-5-yl)sulfonyl)anilino)butanoic acid,    (2S)-2-amino-5-oxo-5-(3,4,5-trimethoxy((1-methyl-1H-indol-5-yl)sulfonyl)anilino)pentanoic acid,    (4S)-4-amino-5-oxo-5-(3,4,5-trimethoxy((1-methyl-1H-indol-5-yl)sulfonyl)anilino)pentanoic acid,    N-((bis(2-methoxyethyl)amino)acetyl)-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    1-methyl-N-(4-morpholinylacetyl)-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    1-methyl-N-((4-methyl-1-piperazinyl)acetyl)-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    N-(4-(aminomethyl)benzoyl)-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide,    1,2,3-trimethoxy-5-((4-methoxybenzyl)sulfanyl)benzene,    1,2,3-trimethoxy-5-((4-methoxybenzyl)sulfinyl)benzene,    1,2,3-trimethoxy-5-((4-methoxybenzyl)sulfonyl)benzene,    1,2,3-trimethoxy-5-((1-(4-methoxyphenyl)-1-methylethyl)sulfonyl)benzene,    2-methoxy-5-(((3,4,5-trimethoxyphenyl)sulfanyl)methyl)aniline,    2-methoxy-5-(((3,4,5-trimethoxyphenyl)sulfinyl)methyl)aniline,    2-methoxy-5-(((3,4,5-trimethoxyphenyl)sulfonyl)methyl)aniline,    2-methoxy-5-(1-methyl-1-((3,4,5-trimethoxyphenyl)sulfonyl)ethyl)aniline,    1,2,3-trimethoxy-5-(((4-methoxyphenyl)sulfanyl)methyl)benzene,    1,2,3-trimethoxy-5-(((4-methoxyphenyl)sulfonyl)methyl)benzene,    1,2,3-trimethoxy-5-(1-((4-methoxyphenyl)sulfonyl)-1-methylethyl)benzene,    2-methoxy-5-((3,4,5-trimethoxybenzyl)sulfonyl)aniline,    2-methoxy-5-((1-methyl-1-(3,4,5-trimethoxyphenyl)ethyl)sulfonyl)aniline, and    1,2,3-trimethoxy-5-((phenylsulfonyl)methyl)benzene.    
     
     
         28 . A compound which is 
 N-((dimethylamino)acetyl)-1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide.