US2004167180A1PendingUtilityA1

Methods for anti-tumor therapy

44
Assignee: COMPASS PHARMACEUTICALS LLCPriority: Aug 30, 2000Filed: Feb 23, 2004Published: Aug 26, 2004
Est. expiryAug 30, 2020(expired)· nominal 20-yr term from priority
Inventors:Irwin Braude
A61P 35/00A61K 31/63A61K 31/18
44
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Claims

Abstract

Disclosed and claimed is a method for treating tumors using sulfonylamino-substituted N-aryl- or heteroarylcarboxamide derivatives.

Claims

exact text as granted — not AI-modified
What is claimed is:  
     
         1 . A method for treating a tumor in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of a compound having the formula:  
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof wherein 
 A 1  is aryl or heteroaryl, each of which may be optionally substituted with one, two or three groups independently selected from halogen, aryl, —CF 3 , —NO 2 , —OH, —O—(C 1 -C 7 )-alkyl, —O—(C 2 -C 4 )-alkyl-O—(C 1 -C 7 )-alkyl, —O-aryl, (C 1 -C 2 )-alkylenedioxy, —NR 5 R 6 , —CN, —CO—NR 5 R 6 , —COOH, —CO—O—(C 1 -C 5 )-alkyl, heterocyclyl, —CHO, —CO—(C 1 -C 10 )-alkyl, —CO-aryl, —CO-heteroaryl, or 
 (C 1 -C 10 )-alkyl, (C 3 -C 10 )-cycloalkyl, (C 1 -C 10 )-alkenyl or (C 1 -C 10 )-alkynyl, each of which is optionally substituted with up to five groups independently selected from halogen, —OH, aryl, heteroaryl, —O—(C 1 -C 10 )-alkyl, —O—(C 1 -C 7 )-alkyl-R 7 , —O-aryl, —O-heteroaryl, —SH, —S—(C 1 -C 10 )-allyl, —S—(C 1 -C 7 )-alkyl-R 7 , —S-aryl, —S-heteroaryl, —P(O)(O—(C 1 -C 5 )-alkyl) 2 , —P(O)(OH) 2 , —CN, —NR 8 R 9 , —CO—NH 2 , —CO—NH—(C 1 -C 3 )-alkyl, —CO—N((C 1 -C 3 )-alkyl) 2 , —COOH, —CO—O—(C 1 -C 5 )-alkyl, heterocyclyl, and oxo;  
 
 A 2  represents a ringed structure consisting of aryl, heteroaryl, heterocyclyl or (C 3 -C 10 )-cycloalkyl;  
 R 2  is —NR 5 R 6 , or 
 aryl, heteroaryl, heterocyclyl, (C 1 -C 10 )-alkyl, (C 3 -C 10 )-cycloalkyl, (C 1 -C 10 )-alkenyl or (C 1 -C 10 )-alkynyl, each of which may be optionally substituted with one, two or three groups selected from halogen, —OH, aryl, heteroaryl, —O—(C 1 -C 10 )-alkyl, —O—(C 1 -C 7 )-alkyl-R 7 , —O-aryl, —O-heteroaryl, —SH, —S—(C 1 -C 10 )-alkyl, —S—(C 1 -C 7 )-alkyl-R 7 , —S-aryl, —S-heteroaryl, —P(O)(Q-(C 1 -C 5 )-alkyl) 2 , —P(O)(OH) 2 , —CN, —NR 8 R 9 , —CO—NH 2 , —CO—NH—(C 1 -C 3 )-alkyl, —CO—N((C 1 -C 3 )-alkyl) 2 , —COOH, —CO—O—(C 1 -C 5 )-alkyl, heterocyclyl, and oxo;  
 
 R 3  is one, two or three substituents independently selected from hydrogen, halogen, —CF 3 , —OH, —O—(C 1 -C 10 )-alkyl, —O—(C 1 -C 7 )-alkyl-R 7 , —O-aryl, —O-heteroaryl, —SH, —S—(C 1 -C 10 )-alkyl, —S—(C 1 -C 7 )-alkyl-R 7 , —S-aryl, —S-heteroaryl, (C 1 -C 3 )-alkylene dioxy, —CN, —NO 2 , —NR 8 R 9 , —CONR 5 R 6 , —COOH, —CO—O—(C 1 -C 5 )-alkyl, heterocyclyl, —S(O) n —(C 1 -C 7 )-alkyl, —S(O) n -aryl, —S(O) n -heteroaryl, —S(O) n —NR 5 R 6 , or 
 (C 1 -C 7 )-alkyl, (C 3 -C 7 )-cycloalkyl, (C 1 -C 7 )-alkenyl or (C 1 -C 7 )-alkynyl, each of which is optionally substituted with up to five groups independently selected from halogen, —OH, aryl, heteroaryl, —O—(C 1 -C 10 )-alkyl, —O—(C 1 -C 7 )-alkyl-R 7 , —O-aryl, —O-heteroaryl, —SH, —S—(C 1 -C 10 )-alkyl, —S—(C 1 -C 7 )-alkyl-R 7 , —S-aryl, —S-heteroaryl, —P(O)(O—(C 1 -C 5 )-alkyl) 2 , —P(O)(OH) 2 , —CN, —NR 8 R 9 , —CO—NH 2 , —CO—NH—(C 1 -C 3 )-alkyl, —CO—N((C 1 -C 3 )-alkyl) 2 , —COOH, —CO—O—(C 1 -C 5 )-alkyl, heterocyclyl, and oxo;  
 
 R 5  and R 6  independently are hydrogen, or 
 (C 1 -C 10 )-alkyl, (C 3 -C 10 )-cycloalkyl, (C 1 -C 10 )-alkenyl or (C 1 -C 10 )-alkynyl, each of which is optionally substituted with one, two or three groups selected from aryl, heteroaryl, heterocyclyl, —CO—(C 1 -C 10 )-alkyl, —CO-aryl, —CO-heteroaryl, —CO-heterocyclyl, —SO 2 —(C 1 -C 10 )-alkyl, —SO 2 -aryl —SO 2 -heteroaryl, or —SO 2 -heterocyclyl; or  
 
 R 5  and R 6  together with the nitrogen atom to which they are attached form a 5, 6, 7 or 8-membered carbocyclic ring up to two of which members are optionally hetero atoms selected from N, O, and S, the carbocyclic ring being optionally substituted with up to five groups selected from halogen, (C 1 -C 5 )-alkyl, (C 3 -C 6 )-cycloalkyl, (C 1 -C 5 )-alkenyl, (C 1 -C 5 )-alkynyl, (C 1 -C 3 )-hydroxyalkyl, (C 1 -C 3 )-alkyl-O—(C 1 -C 4 )-alkyl, aryl, heteroaryl, —CF 3 , —OH, —O—(C 1 -C 7 )-alkyl, —O-aryl, —O-heteroaryl, —O—(C 2 -C 4 )-alkyl-O—(C 1 -C 7 )-alkyl, (C 2 -C 3 )-alkylenedioxy, —NR 8 R 9 , —CN, —CO—NH 2 , —CO—NH—(C 1 -C 3 )-alkyl, —CO—N((C 1 -C 3 )-alkyl) 2 , —COOH, —CO—O—(C 1 -C 5 )-alkyl, —CHO, CO—(C 1 -C 5 )-alkyl, —S(O) n —(C 1 -C 4 )-alkyl, —S(O) n —NH 2 , —S(O) n —NH—(C 1 -C 3 )-alkyl, —S(O) n —N((C 1 -C 3 )-alkyl) 2 , oxo, —(CH 2 ) m —NH 2 , —(CH 2 ) m —NH—(C 1 -C 4 )-alkyl or 
 —(CH 2 ) m —N((C 1 -C 4 )-alkyl) 2 , wherein the two alkyl groups are optionally linked by a single bond and then, together with the nitrogen atom to which they are attached, form a 5, 6, 7 or 8-membered carbocyclic ring in which one member is optionally selected from O, S or NR 5 ;  
 
 R 7  is —OH, —O—(C 1 -C 7 )-alkyl, —NH 2 , —NH—(C 1 -C 4 )-alkyl, or 
 —N((C 1 -C 4 )-alkyl) 2 , wherein the two alkyl groups are optionally linked by a single bond and then, together with the nitrogen atom to which they are attached, form a 5, 6, 7 or 8-membered carbocyclic ring in which one member is optionally selected from O, S or NR 5 ;  
 
 R 8  is hydrogen, or 
 (C 1 -C 7 )-alkyl, (C 3 -C 7 )-cycloalkyl, (C 1 -C 7 )-alkenyl or (C 1 -C 7 )-alkynyl, each of which is optionally substituted with one, two or three groups selected from —OH, —O—(C 1 -C 5 )-alkyl, —NH 2 , —NH—(C 1 -C 4 )-alkyl and —N((C 1 -C 4 )-alkyl) 2 ;  
 
 R 9  is hydrogen, —CO—(C 1 -C 4 )-alkyl, or 
 (C 1 -C 7 )-allyl, (C 3 -C 7 )-cycloalkyl, (C 1 -C 7 )-alkenyl or (C 1 -C 7 )-alkynyl, each of which is optionally substituted with one, two or three groups selected from —OH, —O—(C 1 -C 5 )-alkyl, —NH 2 , —NH—(C 1 -C 4 )-alkyl and —N((C 1 -C 4 )-alkyl) 2 ;  
 
 n is 0, 1, or 2; and  
 m is 2, 3, or 4.  
 
     
     
         2 . A method for treating a tumor in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of a compound having the formula:  
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof wherein 
 A 1  is aryl or heteroaryl, each of which may be optionally substituted with one, two or three groups independently selected from halogen, aryl, —CF 3 , —NO 2 , —OH, —O—(C 1 -C 7 )-alkyl, —O—(C 2 -C 4 )-alkyl-O—(C 1 -C 7 )-alkyl, —O-aryl, (C 1 -C 2 )-alkylenedioxy, —NR 5 R 6 , —CN, —CO—NR 5 R 6 , —COOH, —CO—O—(C 1 -C 5 )-alkyl, heterocyclyl, —CHO, —CO—(C 1 -C 10 )-alkyl, —CO-aryl, —CO-heteroaryl, or 
 (C 1 -C 10 )-alkyl, (C 3 -C 10 )-cycloalkyl, (C 1 -C 10 )-alkenyl or (C 1 -C 10 )-alkynyl, each of which is optionally substituted with up to five groups independently selected from halogen, —OH, aryl, heteroaryl, —O—(C 1 -C 10 )-alkyl, —O—(C 1 -C 7 )-alkyl-R 7 , —O-aryl, —O-heteroaryl, —SH, —S—(C 1 -C 10 )-alkyl, —S—(C 1 -C 7 )-alkyl-R 7 , —S-aryl, —S-heteroaryl, —P(O)(O—(C 1 -C 5 )-alkyl) 2 , —P(O)(OH) 2 , —CN, —NR 8 R 9 , —CO—NH 2 , —CO—NH—(C 1 -C 3 )-alkyl, —CO—N((C 1 -C 3 )-alkyl) 2 , —COOH, —CO—O—(C 1 -C 5 )-alkyl, heterocyclyl, and oxo;  
 
 R 2  is —NR 5 R 6 , or 
 aryl, heteroaryl, heterocyclyl, (C 1 -C 10 )-alkyl, (C 3 -C 10 )-cycloalkyl, (C 1 -C 10 )-alkenyl or (C 1 -C 10 )-alkynyl, each of which may be optionally substituted with one, two or three groups selected from halogen, —OH, aryl, heteroaryl, —O—(C 1 -C 10 )-alkyl, —O—(C 1 -C 7 )-alkyl-R 7 , —O-aryl, —O-heteroaryl, —SH, —S—(C 1 -C 10 )-alkyl, —S—(C 1 -C 7 )-alkyl-R 7 , —S-aryl, —S-heteroaryl, —P(O)(O—(C 1 -C 5 )-alkyl) 2 , —P(O)(OH) 2 , —CN, —NR 8 R 9 , —CO—NH 2 , —CO—NH—(C 1 -C 3 )-alkyl, —CO—N((C 1 -C 3 )-alkyl) 2 , —COOH, —CO—O—(C 1 -C 5 )-alkyl, heterocyclyl, and oxo;  
 
 R 3  is one, two or three substituents independently selected from hydrogen, halogen, —CF 3 , —OH, —O—(C 1 -C 10 )-alkyl, —O—(C 1 -C 7 )-alkyl-R 7 , —O-aryl, —O-heteroaryl, —SH, —S—(C 1 -C 10 )-alkyl, —S—(C 1 -C 7 )-alkyl-R 7 , —S-aryl, —S-heteroaryl, (C 1 -C 3 )-alkylene dioxy, —CN, —NO 2 , —NR 8 R 9 , —CONR 5 R 6 , —COOH, —CO—O—(C 1 -C 5 )-alkyl, heterocyclyl, —S(O) n —(C 1 -C 7 )-alkyl, —S(O) n -aryl, —S(O) n -heteroaryl, —S(O) n —NR 5 R 6 , or 
 (C 1 -C 7 )-alkyl, (C 3 -C 7 )-cycloalkyl, (C 1 -C 7 )-alkenyl or (C 1 -C 7 )-alkynyl, each of which is optionally substituted with up to five groups independently selected from halogen, —OH, aryl, heteroaryl, —O—(C 1 -C 10 )-alkyl, —O—(C 1 -C 7 )-alkyl-R 7 , —O-aryl, —O-heteroaryl, —SH, —S—(C 1 -C 10 )-alkyl, —S—(C 1 -C 7 )-alkyl-R 7 , —S-aryl, —S-heteroaryl, —P(O)(O—(C 1 -C 5 )-alkyl) 2 , —P(O)(OH) 2 , —CN, —NR 8 R 9 , —CO—NH 2 , —CO—NH—(C 1 -C 3 )-alkyl, —CO—N((C 1 -C 3 )-alkyl) 2 , —COOH, —CO—O—(C 1 -C 5 )-alkyl, heterocyclyl, and oxo;  
 
 R 5  and R 6  independently are hydrogen, or 
 (C 1 -C 10 )-alkyl, (C 3 -C 10 )-cycloalkyl, (C 1 -C 10 )-alkenyl or (C 1 -C 10 )-alkynyl, each of which is optionally substituted with one, two or three groups selected from aryl, heteroaryl, heterocyclyl, —CO—(C 1 -C 10 )-alkyl, —CO-aryl, —CO-heteroaryl, —CO-heterocyclyl, —SO 2 —(C 1 -C 10 )-alkyl, —SO 2 -aryl —SO 2 -heteroaryl, or —SO 2 -heterocyclyl; or  
 
 R 5  and R 6  together with the nitrogen atom to which they are attached form a 5, 6, 7 or 8-membered carbocyclic ring up to two of which members are optionally hetero atoms selected from N, O, and S, the carbocyclic ring being optionally substituted with up to five groups selected from halogen, (C 1 -C 5 )-alkyl, (C 3 -C 6 )-cycloalkyl, (C 1 -C 5 )-alkenyl, (C 1 -C 5 )-alkynyl, (C 1 -C 3 )-hydroxyalkyl, (C 1 -C 3 )-alkyl-O—(C 1 -C 4 )-alkyl, aryl, heteroaryl, —CF 3 , —OH, —O—(C 1 -C 7 )-alkyl, —O-aryl, —O-heteroaryl, —O—-(C 2 -C 4 )-alkyl-O—(C 1 -C 7 )-alkyl, (C 2 -C 3 )-alkylenedioxy, —NR 8 R 9 , —CN, —CO—NH 2 , —CO—NH—(C 1 -C 3 )-alkyl, —CO—N((C 1 -C 3 )-alkyl) 2 , —COOH, —CO—O—(C 1 -C 5 )-alkyl, —CHO, CO—(C 1 -C 5 )-allyl, —S(O) n —(C 1 -C 4 )-alkyl, —S(O) n —NH 2 , —S(O) n —NH—(C 1 -C 3 )-alkyl, —S(O) n —N((C 1 -C 3 )-alkyl) 2 , oxo, —(CH 2 ) m —NH 2 , —(CH 2 ) m —NH—(C 1 -C 4 )-alkyl or 
 —(CH 2 ) m —N((C 1 -C 4 )-alkyl) 2 , wherein the two alkyl groups are optionally linked by a single bond and then, together with the nitrogen atom to which they are attached, form a 5, 6, 7 or 8-membered carbocyclic ring in which one member is optionally selected from O, S or NR 5 ;  
 
 R 7  is —OH, —O—(C 1 -C 7 )-alkyl, —NH 2 , —NH—(C 1 -C 4 )-alkyl, or 
 —N((C 1 -C 4 )-alkyl) 2 , wherein the two alkyl groups are optionally linked by a single bond and then, together with the nitrogen atom to which they are attached, form a 5, 6, 7 or 8-membered carbocyclic ring in which one member is optionally selected from O, S or NR 5 ;  
 
 R 8  is hydrogen, or 
 (C 1 -C 7 )-alkyl, (C 3 -C 7 )-cycloalkyl, (C 1 -C 7 )-alkenyl or (C 1 -C 7 )-alkynyl, each of which is optionally substituted with one, two or three groups selected from —OH, —O—(C 1 -C 5 )-alkyl, —NH 2 , —NH—(C 1 -C 4 )-alkyl and —N((C 1 -C 4 )-alkyl) 2 ;  
 
 R 9  is hydrogen, —CO—(C 1 -C 4 )-alkyl, or 
 (C 1 -C 7 )-alkyl, (C 3 -C 7 )-cycloalkyl, (C 1 -C 7 )-alkenyl or (C 1 -C 7 )-alkynyl, each of which is optionally substituted with one, two or three groups selected from —OH, —O—(C 1 -C 5 )-alkyl, —NH 2 , —NH—(C 1 -C 4 )-alkyl and —N((C 1 -C 4 )-alkyl) 2 ;  
 
 n is 0, 1, or 2; and  
 m is 2, 3, or 4.  
 
     
     
         3 . A method for treating a tumor in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of a compound having the formula:  
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof wherein 
 A 1  is aryl or heteroaryl, each of which may be optionally substituted with one, two or three groups independently selected from halogen, aryl, —CF 3 , —NO 2 , —OH, —O—(C 1 -C 7 )-alkyl, —O—(C 2 -C 4 )-alkyl-O—(C 1 -C 7 )-alkyl, —O-aryl, (C 1 -C 2 )-alkylenedioxy, —NR 5 R 6 , —CN, —CO—NR 5 R 6 , —COOH, —CO—O—(C 1 -C 5 )-alkyl, heterocyclyl, —CHO, —CO—(C 1 -C 10 )-alkyl, —CO-aryl, —CO-heteroaryl, or 
 (C 1 -C 10 )-alkyl, (C 3 -C 10 )-cycloalkyl, (C 1 -C 10 )-alkenyl or (C 1 -C 10 )-alkynyl, each of which is optionally substituted with up to five groups independently selected from halogen, —OH, aryl, heteroaryl, —O—(C 1 -C 10 )-alkyl, —O—(C 1 -C 7 )-alkyl-R 7 , —O-aryl, —O-heteroaryl, —SH, —S—(C 1 -C 10 )-alkyl, —S—(C 1 -C 7 )-alkyl-R 7 , —S-aryl, —S-heteroaryl, —P(O)(O—(C 1 -C 5 )-alkyl) 2 , —P(O)(OH) 2 , —CN, —NR 8 R 9 , —CO—NH 2 , —CO—NH—(C 1 -C 3 )-alkyl, —CO—N((C 1 -C 3 )-alkyl) 2 , —COOH, —CO—O—(C 1 -C 5 )-alkyl, heterocyclyl, and oxo;  
 
 R 3  is one, two or three substituents independently selected from hydrogen, halogen, —CF 3 , —OH, —O—(C 1 -C 10 )-alkyl, —O—(C 1 -C 7 )-alkyl-R 7 , —O-aryl, —O-heteroaryl, —SH, —S—(C 1 -C 10 )-alkyl, —S—(C 1 -C 7 )-alkyl-R 7 , —S-aryl, —S-heteroaryl, (C 1 -C 3 )-alkylene dioxy, —CN, —NO 2 , —NR 8 R 9 , —CONR 5 R 6 , —COOH, —CO—O—(C 1 -C 5 )-alkyl, heterocyclyl, —S(O) n —(C 1 -C 7 )-alkyl, —S(O) n -aryl, —S(O) n -heteroaryl, —S(O) n —NR 5 R 6 , or 
 (C 1 -C 7 )-alkyl, (C 3 -C 7 )-cycloalkyl, (C 1 -C 7 )-alkenyl or (C 1 -C 7 )-alkynyl, each of which is optionally substituted with up to five groups independently selected from halogen, —OH, aryl, heteroaryl, —O—(C 1 -C 10 )-alkyl, —O—(C 1 -C 7 )-alkyl-R 7 , —O-aryl, —O-heteroaryl, —SH, —S—(C 1 -C 10 )-alkyl, —S—(C 1 -C 7 )-alkyl-R 7 , —S-aryl, —S-heteroaryl, —P(O)(O—(C 1 -C 5 )-alkyl) 2 , —P(O)(OH) 2 , —CN, —NR 8 R 9 , —CO—NH 2 , —CO—NH—(C 1 -C 3 )-alkyl, —CO—N((C 1 -C 3 )-alkyl) 2 , —COOH, —CO—O—(C 1 -C 5 )-alkyl, heterocyclyl, and oxo;  
 
 R 5  and R 6  independently are hydrogen, or 
 (C 1 -C 10 )-alkyl, (C 3 -C 10 )-cycloalkyl, (C 1 -C 10 )-alkenyl or (C 1 -C 10 )-alkynyl, each of which is optionally substituted with one, two or three groups selected from aryl, heteroaryl, heterocyclyl, —CO—(C 1 -C 10 )-alkyl, —CO-aryl, —CO-heteroaryl, —CO-heterocyclyl, —SO 2 —(C 1 -C 10 )-alkyl, —SO 2 -aryl SO 2 -heteroaryl, or —SO 2 -heterocyclyl; or  
 
 R 5  and R 6  together with the nitrogen atom to which they are attached form a 5, 6, 7 or 8-membered carbocyclic ring up to two of which members are optionally hetero atoms selected from N, O, and S, the carbocyclic ring being optionally substituted with up to five groups selected from halogen, (C 1 -C 5 )-alkyl, (C 3 -C 6 )-cycloalkyl, (C 1 -C 5 )-alkenyl, (C 1 -C 5 )-alkynyl, (C 1 -C 3 )-hydroxyalkyl, (C 1 -C 3 )-alkyl-O—(C 1 -C 4 )-alkyl, aryl, heteroaryl, —CF 3 , —OH, —O—(C 1 -C 7 )-alkyl, —O-aryl, —O-heteroaryl, —O—(C 2 -C 4 )-alkyl-O—(C 1 -C 7 )-alkyl, (C 2 -C 3 )-alkylenedioxy, —NR 8 R 9 , —CN, —CO—NH 2 , —CO—NH—(C 1 -C 3 )-alkyl, —CO—N((C 1 -C 3 )-alkyl) 2 , —COOH, —CO—O—(C 1 -C 5 )-alkyl, —CHO, CO—(C 1 -C 5 )-alkyl, —S(O) n —(C 1 -C 4 )-alkyl, —S(O) n —NH 2 , —S(O) n —NH—(C 1 -C 3 )-alkyl, —S(O) n —N((C 1 -C 3 )-alkyl) 2 , oxo, —(CH 2 ) m —NH 2 , —(CH 2 ) m —NH—(C 1 -C 4 )-alkyl or 
 —(CH 2 ) m —N((C 1 -C 4 )-alkyl) 2 , wherein the two alkyl groups are optionally linked by a single bond and then, together with the nitrogen atom to which they are attached, form a 5, 6, 7 or 8-membered carbocyclic ring in which one member is optionally selected from O, S or NR 5 ;  
 
 R 7  is —OH, —O—(C 1 -C 7 )-alkyl, —NH 2 , —NH—(C 1 -C 4 )-alkyl, or 
 —N((C 1 -C 4 )-alkyl) 2 , wherein the two alkyl groups are optionally linked by a single bond and then, together with the nitrogen atom to which they are attached, form a 5, 6, 7 or 8-membered carbocyclic ring in which one member is optionally selected from O, S or NR 5 ;  
 
 R 8  is hydrogen, or 
 (C 1 -C 7 )-alkyl, (C 3 -C 7 )-cycloalkyl, (C 1 -C 7 )-alkenyl or (C 1 -C 7 )-alkynyl, each of which is optionally substituted with one, two or three groups selected from —OH, —O—(C 1 -C 5 )-alkyl, —NH 2 , —NH—(C 1 -C 4 )-alkyl and —N((C 1 -C 4 )-alkyl) 2 ;  
 
 R 9  is hydrogen, —CO—(C 1 -C 4 )-alkyl, or 
 (C 1 -C 7 )-alkyl, (C 3 -C 7 )-cycloalkyl, (C 1 -C 7 )-alkenyl or (C 1 -C 7 )-alkynyl, each of which is optionally substituted with one, two or three groups selected from —OH, —O—(C 1 -C 5 )-alkyl, —NH 2 , —NH—(C 1 -C 4 )-alkyl and —N((C 1 -C 4 )-alkyl) 2 ;  
 
 n is 0, 1, or 2; and  
 m is 2, 3, or 4.  
 
     
     
         4 . A method for treating a tumor in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of a compound having the formula:  
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof wherein 
 R 2  is —NR 5 R 6 , or 
 aryl, heteroaryl, heterocyclyl, (C 1 -C 10 )-alkyl, (C 3 -C 10 )-cycloalkyl, (C 1 -C 10 )-alkenyl or (C 1 -C 10 )-alkynyl, each of which may be optionally substituted with one, two or three groups selected from halogen, —OH, aryl, heteroaryl, —O—(C 1 -C 10 )-alkyl, —O—(C 1 -C 7 )-alkyl-R 7 , —O-aryl, —O-heteroaryl, —SH, —S—(C 1 -C 10 )-alkyl, —S—(C 1 -C 7 )-alkyl-R 7 , —S-aryl, —S-heteroaryl, —P(O)(O—(C 1 -C 5 )-alkyl) 2 , —P(O)(OH) 2 , —CN, —NR 8 R 9 , —CO—NH 2 , —CO—NH—(C 1 -C 3 )-alkyl, —CO—N((C 1 -C 3 )-alkyl) 2 , —COOH, —CO—O—(C 1 -C 5 )-alkyl, heterocyclyl, and oxo;  
 
 R 3  is one, two or three substituents independently selected from hydrogen, halogen, —CF 3 , —OH, —O—(C 1 -C 10 )-alkyl, —O—(C 1 -C 7 )-alkyl-R 7 , —O-aryl, —O-heteroaryl, —SH, —S—(C 1 -C 10 )-alkyl, —S—(C 1 -C 7 )-alkyl-R 7 , —S-aryl, —S-heteroaryl, (C 1 -C 3 )-alkylene dioxy, —CN, —NO 2 , —NR 8 R 9 , —CONR 5 R 6 , —COOH, —CO—O—(C 1 -C 5 )-alkyl, heterocyclyl, —S(O) n —(C 1 -C 7 )-alkyl, —S(O) n -aryl, —S(O) n -heteroaryl, —S(O) n —NR 5 R 6 , or 
 (C 1 -C 7 )-alkyl, (C 3 -C 7 )-cycloalkyl, (C 1 -C 7 )-alkenyl or (C 1 -C 7 )-alkynyl, each of which is optionally substituted with up to five groups independently selected from halogen, —OH, aryl, heteroaryl, —O—(C 1 -C 10 )-alkyl, —O—(C 1 -C 7 )-alkyl-R 7 , —O-aryl, —O-heteroaryl, —SH, —S—(C 1 -C 10 )-alkyl, —S—(C 1 -C 7 )-alkyl-R 7 , —S-aryl, —S-heteroaryl, —P(O)(O—(C 1 -C 5 )-alkyl) 2 , —P(O)(OH) 2 , —CN, —NR 8 NR 9 , —CO—NH 2 , —CO—NH—(C 1 -C 3 )-alkyl, —CO—N((C 1 -C 3 )-alkyl) 2 , —COOH, —CO—O—(C 1 -C 5 )-alkyl, heterocyclyl, and oxo;  
 
 R 5  and R 6  independently are hydrogen, or 
 (C 1 -C 10 )-alkyl, (C 3 -C 10 )-cycloalkyl, (C 1 -C 10 )-alkenyl or (C 1 -C 10 )-alkynyl, each of which is optionally substituted with one, two or three groups selected from aryl, heteroaryl, heterocyclyl, —CO—(C 1 -C 10 )-alkyl, —CO-aryl, —CO-heteroaryl, —CO-heterocyclyl, —SO 2 —(C 1 -C 10 )-alkyl, —SO 2 -aryl —SO 2 -heteroaryl, or —SO 2 -heterocyclyl; or  
 
 R 5  and R 6  together with the nitrogen atom to which they are attached form a 5, 6, 7 or 8-membered carbocyclic ring up to two of which members are optionally hetero atoms selected from N, O, and S, the carbocyclic ring being optionally substituted with up to five groups selected from halogen, (C 1 -C 5 )-alkyl, (C 3 -C 6 )-cycloalkyl, (C 1 -C 5 )-alkenyl, (C 1 -C 5 )-alkynyl, (C 1 -C 3 )-hydroxyalkyl, (C 1 -C 3 )-alkyl-O—(C 1 -C 4 )-alkyl, aryl, heteroaryl, —CF 3 , —OH, —O—(C 1 -C 7 )-alkyl, —O-aryl, —O-heteroaryl, —O—(C 2 -C 4 )-alkyl-O—(C 1 -C 7 )-alkyl, (C 2 -C 3 )-alkylenedioxy, —NR 8 R 9 , —CN, —CO—NH 2 , —CO—NH—(C 1 -C 3 )-alkyl, —CO—N((C 1 -C 3 )-alkyl) 2 , —COOH, —CO—O—(C 1 -C 5 )-alkyl, —CHO, CO—(C 1 -C 5 )-alkyl, —S(O) n —(C 1 -C 4 )-alkyl, —S(O) n —NH 2 , —S(O) n —NH—(C 1 -C 3 )-alkyl, —S(O) n —N((C 1 -C 3 )-alkyl) 2 , oxo, —(CH 2 ) m —NH 2 , —(CH 2 ) m —NH—(C 1 -C 4 )-alkyl or 
 —(CH 2 ) m —N((C 1 -C 4 )-alkyl) 2 , wherein the two alkyl groups are optionally linked by a single bond and then, together with the nitrogen atom to which they are attached, form a 5, 6, 7 or 8-membered carbocyclic ring in which one member is optionally selected from O, S or NR 5 ;  
 
 R 7  is —OH, —O—(C 1 -C 7 )-alkyl, —NH 2 , —NH—(C 1 -C 4 )-alkyl, or 
 —N((C 1 -C 4 )-alkyl) 2 , wherein the two alkyl groups are optionally linked by a single bond and then, together with the nitrogen atom to which they are attached, form a 5, 6, 7 or 8-membered carbocyclic ring in which one member is optionally selected from O, S or NR 5 ;  
 
 R 8  is hydrogen, or 
 (C 1 -C 7 )-alkyl, (C 3 -C 7 )-cycloalkyl, (C 1 -C 7 )-alkenyl or (C 1 -C 7 )-alkynyl, each of which is optionally substituted with one, two or three groups selected from —OH, —O—(C 1 -C 5 )-alkyl, —NH 2 , —NH—(C 1 -C 4 )-alkyl and —N((C 1 -C 4 )-alkyl) 2 ;  
 
 R 9  is hydrogen, —CO—(C 1 -C 4 )-alkyl, or 
 (C 1 -C 7 )-alkyl, (C 3 -C 7 )-cycloalkyl, (C 1 -C 7 )-alkenyl or (C 1 -C 7 )-alkynyl, each of which is optionally substituted with one, two or three groups selected from —OH, —O—(C 1 -C 5 )-alkyl, —NH 2 , —NH—(C 1 -C 4 )-alkyl and —N((C 1 -C 4 )-alkyl) 2 ;  
 
 n is 0, 1, or 2; and  
 m is 2, 3, or 4.  
 
     
     
         5 . A method for treating a tumor in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of a compound having the formula:  
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof wherein 
 A 1  is aryl or heteroaryl, each of which may be optionally substituted with one, two or three groups independently selected from halogen, aryl, —CF 3 , —NO 2 , —OH, —O—(C 1 -C 7 )-alkyl, —O—(C 2 -C 4 )-alkyl-O—(C 1 -C 7 )-alkyl, —O-aryl, (C 1 -C 2 )-alkylenedioxy, —NR 5 R 6 , —CN, —CO—NR 5 R 6 , —COOH, —CO—O—(C 1 -C 5 )-alkyl, heterocyclyl, —CHO, —CO—(C 1 -C 10 )-alkyl, —CO-aryl, —CO-heteroaryl, or 
 (C 1 -C 10 )-alkyl, (C 3 -C 10 )-cycloalkyl, (C 1 -C 10 )-alkenyl or (C 1 -C 10 )-alkynyl, each of which is optionally substituted with up to five groups independently selected from halogen, —OH, aryl, heteroaryl, —O—(C 1 -C 10 )-alkyl, —O—(C 1 -C 7 )-alkyl-R 7 , —O-aryl, —O-heteroaryl, —SH, —S—(C 1 -C 10 )-alkyl, —S—(C 1 -C 7 )-alkyl-R 7 , —S-aryl, —S-heteroaryl, —P(O)(O—(C 1 -C 5 )-alkyl) 2 , —P(O)(OH) 2 , —CN, —NR 8 R 9 , —CO—NH 2 , —CO—NH—(C 1 -C 3 )-alkyl, —CO—N((C 1 -C 3 )-alkyl) 2 , —COOH, —CO—O—(C 1 -C 5 )-alkyl, heterocyclyl, and oxo;  
 
 R 2  is —NR 5 R 6 , or 
 aryl, heteroaryl, heterocyclyl, (C 1 -C 10 )-alkyl, (C 3 -C 10 )-cycloalkyl, (C 1 -C 10 )-alkenyl or (C 1 -C 10 )-alkynyl, each of which may be optionally substituted with one, two or three groups selected from halogen, —OH, aryl, heteroaryl, —O—(C 1 -C 10 )-alkyl, —O—(C 1 -C 7 )-alkyl-R 7 , —O-aryl, —O-heteroaryl, —SH, —S—(C 1 -C 10 )-alkyl, —S—(C 1 -C 7 )-alkyl-R 7 , —S-aryl, —S-heteroaryl, —P(O)(O—(C 1 -C 5 )-alkyl) 2 , —P(O)(OH) 2 , —CN, —NR 8 R 9 , —CO—NH 2 , —CO—NH—(C 1 -C 3 )-alkyl, —CO—N((C 1 -C 3 )-alkyl) 2 , —COOH, —CO—O—(C 1 -C 5 )-alkyl, heterocyclyl, and oxo;  
 
 R 3  is one, two or three substituents independently selected from hydrogen, halogen, —CF 3 , —OH, —O—(C 1 -C 10 )-alkyl, —O—(C 1 -C 7 )-alkyl-R 7 , —O-aryl, —O-heteroaryl, —SH, —S—(C 1 -C 10 )-alkyl, —S—(C 1 -C 7 )-alkyl-R 7 , —S-aryl, —S-heteroaryl, (C 1 -C 3 )-alkylene dioxy, —CN, —NO 2 , —NR 8 R 9 , —CONR 5 R 6 , —COOH, —CO—O—(C 1 -C 5 )-alkyl, heterocyclyl, —S(O) n —(C 1 -C 7 )-alkyl, —S(O) n -aryl, —S(O) n -heteroaryl, —S(O) n —NR 5 R 6 , or 
 (C 1 -C 7 )-alkyl, (C 3 -C 7 )-cycloalkyl, (C 1 -C 7 )-alkenyl or (C 1 -C 7 )-alkynyl, each of which is optionally substituted with up to five groups independently selected from halogen, —OH, aryl, heteroaryl, —O—(C 1 -C 10 )-alkyl, —O—(C 1 -C 7 )-alkyl-R 7 , —O-aryl, —O-heteroaryl, —SH, —S—(C 1 -C 10 )-alkyl, —S—(C 1 -C 7 )-alkyl-R 7 , —S-aryl, —S-heteroaryl, —P(O)(O—(C 1 -C 5 )-alkyl) 2 , —P(O)(OH) 2 , —CN, —NR 8 R 9 , —CO—NH 2 , —CO—NH—(C 1 -C 3 )-alkyl, —CO—N((C 1 -C 3 )-alkyl) 2 , —COOH, —CO—O—(C 1 -C 5 )-alkyl, heterocyclyl, and oxo;  
 
 R 5  and R 6  independently are hydrogen, or 
 (C 1 -C 10 )-alkyl, (C 3 -C 10 )-cycloalkyl, (C 1 -C 10 )-alkenyl or (C 1 -C 10 )-alkynyl, each of which is optionally substituted with one, two or three groups selected from aryl, heteroaryl, heterocyclyl, —CO—(C 1 -C 10 )-alkyl, —CO-aryl, —CO-heteroaryl, —CO-heterocyclyl, —SO 2 —(C 1 -C 10 )-alkyl, —SO 2 -aryl —SO 2 -heteroaryl, or —SO 2 -heterocyclyl; or  
 
 R 5  and R 6  together with the nitrogen atom to which they are attached form a 5, 6, 7 or 8-membered carbocyclic ring up to two of which members are optionally hetero atoms selected from N, O, and S, the carbocyclic ring being optionally substituted with up to five groups selected from halogen, (C 1 -C 5 )-alkyl, (C 3 -C 6 )-cycloalkyl, (C 1 -C 5 )-alkenyl, (C 1 -C 5 )-alkynyl, (C 1 -C 3 )-hydroxyalkyl, (C 1 -C 3 )-alkyl-O—(C 1 -C 4 )-alkyl, aryl, heteroaryl, —CF 3 , —OH, —O—(C 1 -C 7 )-alkyl, —O-aryl, —O-heteroaryl, —O—(C 2 -C 4 )-alkyl-O—(C 1 -C 7 )-alkyl, (C 2 -C 3 )-alkylenedioxy, —NR 8 R 9 , —CN, —CO—NH 2 , —CO—NH—(C 1 -C 3 )-alkyl, —CO—N((C 1 -C 3 )-alkyl) 2 , —COOH, —CO—O—(C 1 -C 5 )-alkyl, —CHO, CO—(C 1 -C 5 )-alkyl, —S(O) n —(C 1 -C 4 )-alkyl, —S(O) n —NH 2 , —S(O) n —NH—(C 1 -C 3 )-alkyl, —S(O) n —N((C 1 -C 3 )-alkyl) 2 , oxo, —(CH 2 ) m —NH 2 , —(CH 2 ) m —NH—(C 1 -C 4 )-alkyl or 
 —(CH 2 ) m —N((C 1 -C 4 )-alkyl) 2 , wherein the two alkyl groups are optionally linked by a single bond and then, together with the nitrogen atom to which they are attached, form a 5, 6, 7 or 8-membered carbocyclic ring in which one member is optionally selected from O, S or NR 5 ;  
 
 R 7  is —OH, —O—(C 1 -C 7 )-alkyl, —NH 2 , —NH—(C 1 -C 4 )-alkyl, or —N((C 1 -C 4 )-alkyl) 2 , wherein the two alkyl groups are optionally linked by a single bond and then, together with the nitrogen atom to which they are attached, form a 5, 6, 7 or 8-membered carbocyclic ring in which one member is optionally selected from O, S or NR 5 ;  
 R 8  is hydrogen, or 
 (C 1 -C 7 )-alkyl, (C 3 -C 7 )-cycloalkyl, (C 1 -C 7 )-alkenyl or (C 1 -C 7 )-alkynyl, each of which is optionally substituted with one, two or three groups selected from —OH, —O—(C 1 -C 5 )-alkyl, —NH 2 , —NH—(C 1 -C 4 )-alkyl and —N((C 1 -C 4 )-alkyl) 2 ;  
 
 R 9  is hydrogen, —CO—(C 1 -C 4 )-alkyl, or 
 (C 1 -C 7 )-alkyl, (C 3 -C 7 )-cycloalkyl, (C 1 -C 7 )-alkenyl or (C 1 -C 7 )-alkynyl, each of which is optionally substituted with one, two or three groups selected from —OH, —O—(C 1 -C 5 )-alkyl, —NH 2 , —NH—(C 1 -C 4 )-alkyl and —N((C 1 -C 4 )-alkyl) 2 ;  
 
 n is 0, 1, or 2; and  
 m is 2, 3, or 4.  
 
     
     
         6 . A method for treating a tumor in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of a compound having the formula:  
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof wherein 
 A 1  is aryl or heteroaryl, each of which may be optionally substituted with one, two or three groups independently selected from halogen, aryl, —CF 3 , —NO 2 , —OH, —O—(C 1 -C 7 )-alkyl, —O—(C 2 -C 4 )-alkyl-O—(C 1 -C 7 )-alkyl, —O-aryl, (C 1 -C 2 )-alkylenedioxy, —NR 5 R 6 , —CN, —CO—NR 5 R 6 , —COOH, —CO—O—(C 1 -C 5 )-alkyl, heterocyclyl, —CHO, —CO—(C 1 -C 10 )-alkyl, —CO-aryl, —CO-heteroaryl, or 
 (C 1 -C 10 )-alkyl, (C 3 -C 10 )-cycloalkyl, (C 1 -C 10 )-alkenyl or (C 1 -C 10 )-alkynyl, each of which is optionally substituted with up to five groups independently selected from halogen, —OH, aryl, heteroaryl, —O—(C 1 -C 10 )-alkyl, —O—(C 1 -C 7 )-alkyl-R 7 , —O-aryl, —O-heteroaryl, —SH, —S—(C 1 -C 10 )-alkyl, —S—(C 1 -C 7 )—alkyl-R 7 , —S-aryl, —S-heteroaryl, —P(O)(O—(C 1 -C 5 )-alkyl) 2 , —P(O)(OH) 2 , —CN, —NR 8 R 9 , —CO—NH 2 , —CO—NH—(C 1 -C 3 )-alkyl, —CO—N((C 1 -C 3 )-alkyl) 2 , —COOH, —CO—O—(C 1 -C 5 )-alkyl, heterocyclyl, and oxo;  
 
 A 2  represents a ringed structure consisting of aryl, heterocyclyl, heteroaryl or (C 3 -C 10 )-cycloalkyl;  
 R 3  is one, two or three substituents independently selected from hydrogen, halogen, —CF 3 , —OH, —O—(C 1 -C 10 )-alkyl, —O—(C 1 -C 7 )-alkyl-R 7 , —O-aryl, —O-heteroaryl, —SH, —S—(C 1 -C 10 )-alkyl, —S—(C 1 -C 7 )-alkyl-R 7 , —S-aryl, —S-heteroaryl, (C 1 -C 3 )-alkylene dioxy, —CN, —NO 2 , —NR 8 R 9 , —CONR 5 R 6 , —COOH, —CO—O—(C 1 -C 5 )-alkyl, heterocyclyl, —S(O) n —(C 1 -C 7 )-alkyl, —S(O) n -aryl, —S(O) n -heteroaryl, —S(O) n —NR 5 R 6 , or 
 (C 1 -C 7 )-alkyl, (C 3 -C 7 )-cycloalkyl, (C 1 -C 7 )-alkenyl or (C 1 -C 7 )-alkynyl, each of which is optionally substituted with up to five groups independently selected from halogen, —OH, aryl, heteroaryl, —O—(C 1 -C 10 )-alkyl, —O—(C 1 -C 7 )-alkyl-R 7 , —O-aryl, —O-heteroaryl, —SH, —S—(C 1 -C 10 )-alkyl, —S—(C 1 -C 7 )-alkyl-R 7 , —S-aryl, —S-heteroaryl, —P(O)(O—(C 1 -C 5 )-alkyl) 2 , —P(O)(OH) 2 , —CN, —NR 8 R 9 , —CO—NH 2 , —CO—NH—(C 1 -C 3 )-alkyl, —CO—N((C 1 -C 3 )-alkyl) 2 , —COOH, —CO—O—(C 1 -C 5 )-alkyl, heterocyclyl, and oxo;  
 
 R 5  and R 6  independently are hydrogen, or 
 (C 1 -C 10 )-alkyl, (C 3 -C 10 )-cycloalkyl, (C 1 -C 10 )-alkenyl or (C 1 -C 10 )-alkynyl, each of which is optionally substituted with one, two or three groups selected from aryl, heteroaryl, heterocyclyl, —CO—(C 1 -C 10 )-alkyl, —CO-aryl, —CO-heteroaryl, —CO-heterocyclyl, —SO 2 —(C 1 -C 10 )-alkyl, —SO 2 -aryl —SO 2 -heteroaryl, or —SO 2 -heterocyclyl; or  
 
 R 5  and R 6  together with the nitrogen atom to which they are attached form a 5, 6, 7 or 8-membered carbocyclic ring up to two of which members are optionally hetero atoms selected from N, O, and S, the carbocyclic ring being optionally substituted with up to five groups selected from halogen, (C 1 -C 5 )-alkyl, (C 3 -C 6 )-cycloalkyl, (C 1 -C 5 )-alkenyl, (C 1 -C 5 )-alkynyl, (C 1 -C 3 )-hydroxyalkyl, (C 1 -C 3 )-alkyl-O—(C 1 -C 4 )-alkyl, aryl, heteroaryl, —CF 3 , —OH, —O—(C 1 -C 7 )-alkyl, —O-aryl, —O-heteroaryl, —O—(C 2 -C 4 )-alkyl-O—(C 1 -C 7 )-alkyl, (C 2 -C 3 )-alkylenedioxy, —NR 8 R 9 , —CN, —CO—NH 2 , —CO—NH—(C 1 -C 3 )-alkyl, —CO—N((C 1 -C 3 )-alkyl) 2 , —COOH, —CO—O—(C 1 -C 5 )-alkyl, —CHO, CO—(C 1 -C 5 )-alkyl, —S(O) n —(C 1 -C 4 )-alkyl, —S(O) n —NH 2 , —S(O) n —NH—(C 1 -C 3 )-alkyl, —S(O) n —N((C 1 -C 3 )-alkyl) 2 , oxo, —(CH 2 ) m —NH 2 , —(CH 2 ) m —NH—(C 1 -C 4 )-alkyl or 
 —(CH 2 ) m —N((C 1 -C 4 )-alkyl) 2 , wherein the two alkyl groups are optionally linked by a single bond and then, together with the nitrogen atom to which they are attached, form a 5, 6, 7 or 8-membered carbocyclic ring in which one member is optionally selected from O, S or NR 5 ;  
 
 R 7  is —OH, —O—(C 1 -C 7 )-alkyl, —NH 2 , —NH—(C 1 -C 4 )-alkyl, or 
 —N((C 1 -C 4 )-alkyl) 2 , wherein the two alkyl groups are optionally linked by a single bond and then, together with the nitrogen atom to which they are attached, form a 5, 6, 7 or 8-membered carbocyclic ring in which one member is optionally selected from O, S or NR 5 ;  
 
 R 8  is hydrogen, or 
 (C 1 -C 7 )-alkyl, (C 3 -C 7 )-cycloalkyl, (C 1 -C 7 )-alkenyl or (C 1 -C 7 )-alkynyl, each of which is optionally substituted with one, two or three groups selected from —OH, —O—(C 1 -C 5 )-alkyl, —NH 2 , —NH—(C 1 -C 4 )-alkyl and —N((C 1 -C 4 )-alkyl) 2 ;  
 
 R 9  is hydrogen, —CO—(C 1 -C 4 )-alkyl, or 
 (C 1 -C 7 )-alkyl, (C 3 -C 7 )-cycloalkyl, (C 1 -C 7 )-alkenyl or (C 1 -C 7 )-alkynyl, each of which is optionally substituted with one, two or three groups selected from —OH, —O—(C 1 -C 5 )-alkyl, —NH 2 , —NH—(C 1 -C 4 )-alkyl and —N((C 1 -C 4 )-alkyl) 2 ;  
 
 n is 0, 1, or 2; and  
 m is 2, 3, or 4.  
 
     
     
         7 . A method for treating a tumor in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of a compound having the formula:  
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof wherein 
 A 1  is aryl or heteroaryl, each of which may be optionally substituted with one, two or three groups independently selected from halogen, aryl, —CF 3 , —NO 2 , —OH, —O—(C 1 -C 7 )-alkyl, —O—(C 2 -C 4 )-alkyl-O—(C 1 -C 7 )-alkyl, —O-aryl, (C 1 -C 2 )-alkylenedioxy, —NR 5 R 6 , —CN, —CO—NR 5 R 6 , —COOH, —CO—O—(C 1 -C 5 )-alkyl, heterocyclyl, —CHO, —CO—(C 1 -C 10 )-alkyl, —CO-aryl, —CO-heteroaryl, or 
 (C 1 -C 10 )-alkyl, (C 3 -C 10 )-cycloalkyl, (C 1 -C 10 )-alkenyl or (C 1 -C 10 )-alkynyl, each of which is optionally substituted with up to five groups independently selected from halogen, —OH, aryl, heteroaryl, —O—(C 1 -C 10 )-alkyl, —O—(C 1 -C 7 )-alkyl-R 7 , —O-aryl, —O-heteroaryl, —SH, —S—(C 1 -C 10 )-alkyl, —S—(C 1 -C 7 )-alkyl-R 7 , —S-aryl, —S-heteroaryl, —P(O)(O—(C 1 -C 5 )-alkyl) 2 , —P(O)(OH) 2 , —CN, —NR 8 R 9 , —CO—NH 2 , —CO—NH—(C 1 -C 3 )-alkyl, —CO—N((C 1 -C 3 )-alkyl) 2 , —COOH, —CO—O—(C 1 -C 5 )-alkyl, heterocyclyl, and oxo;  
 
 A 2  represents a ringed structure consisting of aryl, heteroaryl, heterocyclyl or (C 3 -C 10 )-cycloalkyl;  
 R 2  is —NR 5 R 6 , or 
 aryl, heteroaryl, heterocyclyl, (C 1 -C 10 )-alkyl, (C 3 -C 10 )-cycloalkyl, (C 1 -C 10 )-alkenyl or (C 1 -C 10 )-alkynyl, each of which may be optionally substituted with one, two or three groups selected from halogen, —OH, aryl, heteroaryl, —O—(C 1 -C 10 )-alkyl, —O—(C 1 -C 7 )-alkyl-R 7 , —O-aryl, —O-heteroaryl, —SH, —S—(C 1 -C 10 )-alkyl, —S—(C 1 -C 7 )-alkyl-R 7 , —S-aryl, —S-heteroaryl, —P(O)(O—(C 1 -C 5 )-alkyl) 2 , —P(O)(OH) 2 , —CN, —NR 8 R 9 , —CO—NH 2 , —CO—NH—(C 1 -C 3 )-alkyl, —CO—N((C 1 -C 3 )-alkyl) 2 , —COOH, —CO—O—(C 1 -C 5 )-alkyl, heterocyclyl, and oxo;  
 
 R 3  is one, two or three substituents independently selected from hydrogen, halogen, —CF 3 , —OH, —O—(C 1 -C 10 )-alkyl, —O—(C 1 -C 7 )-alkyl-R 7 , —O-aryl, —O-heteroaryl, —SH, —S—(C 1 -C 10 )-alkyl, —S—(C 1 -C 7 )-alkyl-R 7 , —S-aryl, —S-heteroaryl, (C 1 -C 3 )-alkylene dioxy, —CN, —NO 2 , —NR 8 R 9 , —CONR 5 R 6 , —COOH, —CO—O—(C 1 -C 5 )-alkyl, heterocyclyl, —S(O) n —(C 1 -C 7 )-alkyl, —S(O) n -aryl, —S(O) n -heteroaryl, —S(O) n —NR 5 R 6 , or 
 (C 1 -C 7 )-alkyl, (C 3 -C 7 )-cycloalkyl, (C 1 -C 7 )-alkenyl or (C 1 -C 7 )-alkynyl, each of which is optionally substituted with up to five groups independently selected from halogen, —OH, aryl, heteroaryl, —O—(C 1 -C 10 )-alkyl, —O—(C 1 -C 7 )-alkyl-R 7 , —O-aryl, —O-heteroaryl, —SH, —S—(C 1 -C 10 )-alkyl, —S—(C 1 -C 7 )-alkyl-R 7 , —S-aryl, —S-heteroaryl, —P(O)(O—(C 1 -C 5 )-alkyl) 2 , —P(O)(OH) 2 , —CN, —NR 8 R 9 , —CO—NH 2 , —CO—NH—(C 1 -C 3 )-alkyl, —CO—N((C 1 -C 3 )-alkyl) 2 , —COOH, —CO—O—(C 1 -C 5 )-alkyl, heterocyclyl, and oxo;  
 
 R 5  and R 6  independently are hydrogen, or 
 (C 1 -C 10 )-alkyl, (C 3 -C 10 )-cycloalkyl, (C 1 -C 10 )-alkenyl or (C 1 -C 10 )-alkynyl, each of which is optionally substituted with one, two or three groups selected from aryl, heteroaryl, heterocyclyl, —CO—(C 1 -C 10 )-alkyl, —CO-aryl, —CO-heteroaryl, —CO-heterocyclyl, —SO 2 —(C 1 -C 10 )-alkyl, —SO 2 -aryl —SO 2 -heteroaryl, or —SO 2 -heterocyclyl; or  
 
 R 5  and R 6  together with the nitrogen atom to which they are attached form a 5, 6, 7 or 8-membered carbocyclic ring up to two of which members are optionally hetero atoms selected from N, O, and S, the carbocyclic ring being optionally substituted with up to five groups selected from halogen, (C 1 -C 5 )-alkyl, (C 3 -C 6 )-cycloalkyl, (C 1 -C 5 )-alkenyl, (C 1 -C 5 )-alkynyl, (C 1 -C 3 )-hydroxyalkyl, (C 1 -C 3 )-alkyl-O—(C 1 -C 4 )-alkyl, aryl, heteroaryl, —CF 3 , —OH, —O—(C 1 -C 7 )-alkyl, —O-aryl, —O-heteroaryl, —O—(C 2 -C 4 )-alkyl-O—(C 1 -C 7 )-alkyl, (C 2 -C 3 )-alkylenedioxy, —NR 8 R 9 , —CN, —CO—NH 2 , —CO—NH—(C 1 -C 3 )-alkyl, —CO—N((C 1 -C 3 )-alkyl) 2 , —COOH, —CO—O—(C 1 -C 5 )-alkyl, —CHO, CO—(C 1 -C 5 )-alkyl, —S(O) n —(C 1 -C 4 )-alkyl, —S(O) n —NH 2 , —S(O) n —NH—(C 1 -C 3 )-alkyl, —S(O) n —N((C 1 -C 3 )-alkyl) 2 , oxo, —(CH 2 ) m —NH 2 , —(CH 2 ) m —NH—(C 1 -C 4 )-alkyl or 
 —(CH 2 ) m —N((C 1 -C 4 )-alkyl) 2 , wherein the two alkyl groups are optionally linked by a single bond and then, together with the nitrogen atom to which they are attached, form a 5, 6, 7 or 8-membered carbocyclic ring in which one member is optionally selected from O, S or NR 5 ;  
 
 R 7  is —OH, —O—(C 1 -C 7 )-alkyl, —NH 2 , —NH—(C 1 -C 4 )-alkyl, or 
 —N((C 1 -C 4 )-alkyl) 2 , wherein the two alkyl groups are optionally linked by a single bond and then, together with the nitrogen atom to which they are attached, form a 5, 6, 7 or 8-membered carbocyclic ring in which one member is optionally selected from O, S or NR 5 ;  
 
 R 8  is hydrogen, or 
 (C 1 -C 7 )-alkyl, (C 3 -C 7 )-cycloalkyl, (C 1 -C 7 )-alkenyl or (C 1 -C 7 )-alkynyl, each of which is optionally substituted with one, two or three groups selected from —OH, —O—(C 1 -C 5 )-alkyl, —NH 2 , —NH—(C 1 -C 4 )-alkyl and —N((C 1 -C 4 )-alkyl) 2 ;  
 
 R 9  is hydrogen, —CO—(C 1 -C 4 )-alkyl, or 
 (C 1 -C 7 )-alkyl, (C 3 -C 7 )-cycloalkyl, (C 1 -C 7 )-alkenyl or (C 1 -C 7 )-alkynyl, each of which is optionally substituted with one, two or three groups selected from —OH, —O—(C 1 -C 5 )-alkyl, —NH 2 , —NH—(C 1 -C 4 )-alkyl and —N((C 1 -C 4 )-alkyl) 2 ;  
 
 n is 0, 1, or 2; and  
 m is 2, 3, or 4.  
 
     
     
         8 . The method according to  claim 1  wherein the compound is selected from 
 5-chloro-2-{[(4-chlorophenyl)sulfonyl]amino}-N-(4-chlorophenyl)benzamide;  
 5-bromo-2-{[(4-chlorophenyl)sulfonyl]amino}-N-(4-chlorophenyl)benzamide;  
 (5-bromo-2-{[(4-chloro-3-nitrophenyl)sulfonyl]amino}phenyl)-N-(4-chlorophenyl) carboxamide;  
 N-(3,4-dichlorophenyl)(5-chloro-2-{[(4-chlorophenyl)sulfonyl]amino}phenyl) carboxamide; and  
 N-(4-chlorophenyl)(3-{[(4-chlorophenyl)sulfonyl]amino}(2-naphthyl))carboxamide.  
 
     
     
         9 . The method of  claim 1  wherein the tumor is selected from sarcoma, carcinoma, and mesothelioma.  
     
     
         10 . The method of  claim 2  wherein the tumor is selected from sarcoma, carcinoma, and mesothelioma.  
     
     
         11 . The method of  claim 3  wherein the tumor is selected from sarcoma, carcinoma, and mesothelioma.  
     
     
         12 . The method of  claim 4  wherein the tumor is selected from sarcoma, carcinoma, and mesothelioma.  
     
     
         13 . The method of  claim 5  wherein the tumor is selected from sarcoma, carcinoma, and mesothelioma.  
     
     
         14 . The method of  claim 6  wherein the tumor is selected from sarcoma, carcinoma, and mesothelioma.  
     
     
         15 . The method of  claim 7  wherein the tumor is selected from sarcoma, carcinoma, and mesothelioma.  
     
     
         16 . The method of  claim 8  wherein the tumor is selected from sarcoma, carcinoma, and mesothelioma.

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