Substituted Hydrophobic Benzene Sulfonamide Thiazole Compounds for Use in Treating Cancer

Abstract

The present invention relates to compound of general formula (I) R 1 is selected from H, aryl and alkyl, R 2 is selected from H, alkyl, aryl and CO—R 6 ; R 3 is selected from H, halogen, alkyl, alkenyl, alkynyl, aryl, NHR 7 , NR 7 R 8 , OR 7 and SR 7 ; R 4 is selected from (C 6 -C 12 ) alkyl, (C 2 -C 12 ) alkenyl, (C 2 -C 12 ) alkynyl and (C 6 -C 10 ) aryl, R 5 represents H, R 6 , aryl, OH, OR 6 , O-aryl, SH, SR 6 , S-aryl, CN, NO 2 , CF 3 , COOR 6 , SO 2 NR 6 R 7 , CONR 6 R 7 , NH 2 , NHR 6 , NH-aryl, NR 6 R 7 , NHCOR 6 or aminoacyl; R 6 is alkyl optionally substituted with halogen, OH, SH, NH 2 , O-alkyl, S-alkyl, NH-alkyl or NH-di(alkyl); R 7 and R 8 identical or different are H or alkyl optionally substituted with halogen, OH, SH, NH 2 , O-alkyl, S-alkyl, NH-alkyl or NH-di (alkyl), their pharmaceutically acceptable salts and/or isomers, tautomers, solvates or isotopic variations thereof. The compounds are useful for the treatment of cancers.

1 - 12 . (canceled) 
     
     
         13 . A method of treating pancreas, prostate, breast and colon cancers in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a compound of general formula (I) 
       
         
           
           
               
               
           
         
       
       wherein
 R 1  is selected from H, aryl and alkyl; 
 R 2  is selected from H, alkyl, aryl and CO—R 6 ; 
 R 3  is selected from H, halogen, alkyl, alkenyl, alkynyl, aryl, NHR 7 , NR 7 R 8 , OR 7  and SR 7 ; 
 R 4  is selected from (C 6 -C 12 ) alkyl, (C 2 -C 12 ) alkenyl, (C 2 -C 12 ) alkynyl and (C 6 -C 10 ) aryl, wherein aryl is unsubstituted or substituted by 1 to 5 alkyl groups, wherein the alkyl, alkenyl and alkynyl groups are linear, branched or cyclic and wherein the alkynyl group is optionally substituted with one to three OH groups; 
 R 5  is selected from H, R 6 , aryl, OH, OR 6 , O-aryl, SH, SR 6 , S-aryl, CN, NO 2 , CF 3 , COOR 6 , SO 2 NR 7 R 8 , CONR 7 R 8 , NH 2 , NHR 6 , NH-aryl, NR 7 R 8 , NHCOR 6  and aminoacyl; 
 R 6  is alkyl optionally substituted with halogen, OH, SH, NH 2 , O-alkyl, S-alkyl, NH-alkyl or NH-di(alkyl); 
 R 7  and R 8  identical or different are H or alkyl optionally substituted with halogen, OH, SH, NH 2 , O-alkyl, S-alkyl, NH-alkyl or NH-di (alkyl); 
 
       or pharmaceutically acceptable salts, isomers, tautomers, solvates or isotopic variations thereof; 
     
     
         14 . The method according to  claim 13 , wherein the cancer is pancreas cancer. 
     
     
         15 . The method according to  claim 13 , wherein the cancer is prostate cancer. 
     
     
         16 . The method according to  claim 13 , wherein the cancer is breast cancer. 
     
     
         17 . The method according to  claim 13 , wherein the cancer is colon cancer. 
     
     
         18 . The method according to  claim 13 , wherein R 1  is H. 
     
     
         19 . The method according to  claim 13 , wherein R 2  is selected from H, methyl or COCH 3 . 
     
     
         20 . The method according to  claim 13 , wherein R 3  is H. 
     
     
         21 . The method according to  claim 13 , wherein R 4  is
 (C 6 -C 12 ) alkyl, or   (C 6 -C 10 ) aryl, or   CH═CHR 9 , wherein R 9  is (C 1 -C 12 ) alkyl, or   C≡CR 10 , wherein R 10  is selected from H, C 1 -C 8  alkyl, hydroxy (C 1 -C 8 ) alkyl, cyclo (C 3 -C 8 ) alkyl and hydroxyl-cyclo (C 3 -C 8  alkyl).   
     
     
         22 . The method according to  claim 19 , wherein (C 6 -C 12 ) alkyl is hexyl, heptyl or octyl. 
     
     
         23 . The method according to  claim 19 , wherein (C 6 -C 10 ) aryl is phenyl, cyclopentyl, or cyclohexyl. 
     
     
         24 . The method according to  claim 19 , wherein R 9  is an hexyl. 
     
     
         25 . The method according to  claim 13 , wherein R 4  is in the meta or para position with respect to the sulfonyl group. 
     
     
         26 . The method according to  claim 13  wherein the compound is selected from:
 N-(4-(3-(4-(oct-1-ynyl)phenylsulfonamido)phenyl)thiazol-2-yl)acetamide, 
 N-(4-(3-(3-(oct-1-ynyl)phenylsulfonamido)phenyl)thiazol-2-yl)acetamide, 
 N-(4-(3-(3-(3-hydroxyprop-1-ynyl)phenylsulfonamido)phenyl)thiazol-2-yl)acetamide, 
 N-(4-(3-(3-((trimethylsilyl)ethynyl)phenylsulfonamido)phenyl)thiazol-2-yl)acetamide, 
 N-(4-(3-(3-ethynylphenylsulfonamido)phenyl)thiazol-2-yl)acetamide, 
 N-(3-(2-aminothiazol-4-yl)phenyl)-4-(oct-1-ynyl)benzenesulfonamide, 
 N-(3-(2-(methylamino)thiazol-4-yl)phenyl)-4-(oct-1-ynyl)benzenesulfonamide, 
 4-(oct-1-ynyl)-N-(3-(2-(phenylamino)thiazol-4-yl)phenyl)benzenesulfonamide, 
 N-(4-(3-((4-(cyclohexylethynyl)phenyl)sulfonamido)phenyl)thiazol-2-yl)acetamide, 
 N-(4-(3-([1,1′-biphenyl]-4-sulfonamido)phenyl)thiazol-2-yl)acetamide, 
 N-(4-(3-((2,3-dihydro-1H-indene)-5-sulfonamido)phenyl)thiazol-2-yl)acetamide, 
 N-(4-(3-((4′-methyl-[1,1′-biphenyl])-4-sulfonamido)phenyl)thiazol-2-yl)acetamide, 
 N-(4-(3-((4-octylphenyl)sulfonamido)phenyl)thiazol-2-yl)acetamide, 
 N-(4-(3-((4-hexylphenyl)sulfonamido)phenyl)thiazol-2-yl)acetamide, 
 N-(4-(3-((4-(3-hydroxyprop-1-yn-1-yl)phenyl)sulfonamido)phenyl)thiazol-2-yl)acetamide, 
 (Z)—N-(4-(3-((4-(oct-1-en-1-yl)phenyl)sulfonamido)phenyl)thiazol-2-yl)acetamide, and 
 N-(4-(3-((4-ethynylphenyl)sulfonamido)phenyl)thiazol-2-yl)acetamide. 
 
     
     
         27 . The method according to  claim 13 , wherein the patient is an animal or a human.