Methods for anti-tumor therapy

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:

• 16
• or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof wherein
• A1 is aryl or heteroaryl, each of which may be optionally substituted with one, two or three groups independently selected from halogen, aryl, —CF3, —NO2, —OH, —O—(C1-C7)-alkyl, —O—(C2-C4)-alkyl-O—(C1-C7)-alkyl, —O-aryl, (C1-C2)-alkylenedioxy, —NR5R6, —CN, —CO—NR5R6, —COOH, —CO—O—(C1-C5)-alkyl, heterocyclyl, —CHO, —CO—(C1-C10)-alkyl, —CO-aryl, —CO-heteroaryl, or
• (C1-C10)-alkyl, (C3-C10)-cycloalkyl, (C1-C10)-alkenyl or (C1-C10)-alkynyl, each of which is optionally substituted with up to five groups independently selected from halogen, —OH, aryl, heteroaryl, —O—(C1-C10)-alkyl, —O—(C1-C7)-alkyl-R7, —O-aryl, —O-heteroaryl, —SH, —S—(C1-C10)-alkyl, —S—(C1-C7)-alkyl-R7, —S-aryl, —S-heteroaryl, —P(O)(O—(C1-C5)-alkyl)2, —P(O)(OH)2, —CN, —NR8R9, —CO—NH2, —CO—NH—(C1-C3)-alkyl, —CO—N((C1-C3)-alkyl)2, —COOH, —CO—O—(C1-C5)-alkyl, heterocyclyl, and oxo;
• R2 is —NR5R6, or
• aryl, heteroaryl, heterocyclyl, (C1-C10)-alkyl, (C3-C10)-cycloalkyl, (C1-C10)-alkenyl or (C1-C10)-alkynyl, each of which may be optionally substituted with one, two or three groups selected from halogen, —OH, aryl, heteroaryl, —O—(C1-C10)-alkyl, —O—(C1-C7)-alkyl-R7, —O-aryl, —O-heteroaryl, —SH, —S—(C1-C10)-alkyl, —S—(C1-C7)-alkyl-R7, —S-aryl, —S-heteroaryl, —P(O)(O—(C1-C5)-alkyl)2, —P(O)(OH)2, —CN, —NR8R9, —CO—NH2, —CO—NH—(C1-C3)-alkyl, —CO—N((C1-C3)-alkyl)2, —COOH, —CO—O—(C1-C5)-alkyl, heterocyclyl, and oxo;
• R3 is one, two or three substituents independently selected from hydrogen, halogen, —CF3, —OH, —O—(C1-C10)-alkyl, —O—(C1-C7)-alkyl-R7, —O-aryl, —O-heteroaryl, —SH, —S—(C1-C10)-alkyl, —S—(C1-C7)-alkyl-R7, —S-aryl, —S-heteroaryl, (C1-C3)-alkylene dioxy, —CN, —NO2, —NR8R9, —CONR5R6, —COOH, —CO—O—(C1-C5)-alkyl, heterocyclyl, —S(O)n—(C1-C7)-alkyl, —S(O)n-aryl, —S(O)n-heteroaryl, —S(O)n—NR5R6, or
• (C1-C7)-alkyl, (C3-C7)-cycloalkyl, (C1-C7)-alkenyl or (C1-C7)-alkynyl, each of which is optionally substituted with up to five groups independently selected from halogen, —OH, aryl, heteroaryl, —O—(C1-C10)-alkyl, —O—(C1-C7)-alkyl-R7, —O-aryl, —O-heteroaryl, —SH, —S—(C1-C10)-alkyl, —S—(C1-C7)-alkyl-R7, —S-aryl, —S-heteroaryl, —P(O)(O—(C1-C5)-alkyl)2, —P(O)(OH)2, —CN, —NR8R9, —CO—NH2, —CO—NH—(C1-C3)-alkyl, —CO—N((C1-C3)-alkyl)2, —COOH, —CO—O—(C1-C5)-alkyl, heterocyclyl, and oxo;
• R5 and R6 independently are hydrogen, or
• (C1-C10)-alkyl, (C3-C10)-cycloalkyl, (C1-C10)-alkenyl or (C1-C10)-alkynyl, each of which is optionally substituted with one, two or three groups selected from aryl, heteroaryl, heterocyclyl, —CO—(C1-C10)-alkyl, —CO-aryl, —CO-heteroaryl, —CO-heterocyclyl, —SO2—(C1-C10)-alkyl, —SO2-aryl —SO2-heteroaryl, or —SO2-heterocyclyl;
• or
• R5 and R6 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, (C1-C5)-alkyl, (C3-C6)-cycloalkyl, (C1-C5)-alkenyl, (C1-C5)-alkynyl, (C1-C3)-hydroxyalkyl, (C1-C3)-alkyl-O—(C1-C4)-alkyl, aryl, heteroaryl, —CF3, —OH, —O—(C1-C7)-alkyl, —O-aryl, —O-heteroaryl, —O—-(C2-C4)-alkyl-O—(C1-C7)-alkyl, (C2-C3)-alkylenedioxy, —NR8R9, —CN, —CO—NH2, —CO—NH—(C1-C3)-alkyl, —CO—N((C1-C3)-alkyl)2, —COOH, —CO—O—(C1-C5)-alkyl, —CHO, CO—(C1-C5)-allyl, —S(O)n—(C1-C4)-alkyl, —S(O)n—NH2, —S(O)n—NH—(C1-C3)-alkyl, —S(O)n—N((C1-C3)-alkyl)2, oxo, —(CH2)m—NH2, —(CH2)m—NH—(C1-C4)-alkyl or
• —(CH2)m—N((C1-C4)-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 NR5;
• R7 is —OH, —O—(C1-C7)-alkyl, —NH2, —NH—(C1-C4)-alkyl, or
• —N((C1-C4)-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 NR5;
• R8 is hydrogen, or
• (C1-C7)-alkyl, (C3-C7)-cycloalkyl, (C1-C7)-alkenyl or (C1-C7)-alkynyl, each of which is optionally substituted with one, two or three groups selected from —OH, —O—(C1-C5)-alkyl, —NH2, —NH—(C1-C4)-alkyl and —N((C1-C4)-alkyl)2;
• R9 is hydrogen, —CO—(C1-C4)-alkyl, or
• (C1-C7)-alkyl, (C3-C7)-cycloalkyl, (C1-C7)-alkenyl or (C1-C7)-alkynyl, each of which is optionally substituted with one, two or three groups selected from —OH, —O—(C1-C5)-alkyl, —NH2, —NH—(C1-C4)-alkyl and —N((C1-C4)-alkyl)2;
• n is 0, 1, or 2;
• and
• m is 2, 3, or 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:

• 17
• or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof wherein
• A1 is aryl or heteroaryl, each of which may be optionally substituted with one, two or three groups independently selected from halogen, aryl, —CF3, —NO2, —OH, —O—(C1-C7)-alkyl, —O—(C2-C4)-alkyl-O—(C1-C7)-alkyl, —O-aryl, (C1-C2)-alkylenedioxy, —NR5R6, —CN, —CO—NR5R6, —COOH, —CO—O—(C1-C5)-alkyl, heterocyclyl, —CHO, —CO—(C1-C10)-alkyl, —CO-aryl, —CO-heteroaryl, or
• (C1-C10)-alkyl, (C3-C10)-cycloalkyl, (C1-C10)-alkenyl or (C1-C10)-alkynyl, each of which is optionally substituted with up to five groups independently selected from halogen, —OH, aryl, heteroaryl, —O—(C1-C10)-alkyl, —O—(C1-C7)-alkyl-R7, —O-aryl, —O-heteroaryl, —SH, —S—(C1-C10)-alkyl, —S—(C1-C7)-alkyl-R7, —S-aryl, —S-heteroaryl, —P(O)(O—(C1-C5)-alkyl)2, —P(O)(OH)2, —CN, —NR8R9, —CO—NH2, —CO—NH—(C1-C3)-alkyl, —CO—N((C1-C3)-alkyl)2, —COOH, —CO—O—(C1-C5)-alkyl, heterocyclyl, and oxo;
• R3 is one, two or three substituents independently selected from hydrogen, halogen, —CF3, —OH, —O—(C1-C10)-alkyl, —O—(C1-C7)-alkyl-R7, —O-aryl, —O-heteroaryl, —SH, —S—(C1-C10)-alkyl, —S—(C1-C7)-alkyl-R7, —S-aryl, —S-heteroaryl, (C1-C3)-alkylene dioxy, —CN, —NO2, —NR8R9, —CONR5R6, —COOH, —CO—O—(C1-C5)-alkyl, heterocyclyl, —S(O)n—(C1-C7)-alkyl, —S(O)n-aryl, —S(O)n-heteroaryl, —S(O)n—NR5R6, or
• (C1-C7)-alkyl, (C3-C7)-cycloalkyl, (C1-C7)-alkenyl or (C1-C7)-alkynyl, each of which is optionally substituted with up to five groups independently selected from halogen, —OH, aryl, heteroaryl, —O—(C1-C10)-alkyl, —O—(C1-C7)-alkyl-R7, —O-aryl, —O-heteroaryl, —SH, —S—(C1-C10)-alkyl, —S—(C1-C7)-alkyl-R7, —S-aryl, —S-heteroaryl, —P(O)(O—(C1-C5)-alkyl)2, —P(O)(OH)2, —CN, —NR8R9, —CO—NH2, —CO—NH—(C1-C3)-alkyl, —CO—N((C1-C3)-alkyl)2, —COOH, —CO—O—(C1-C5)-alkyl, heterocyclyl, and oxo;
• R5 and R6 independently are hydrogen, or
• (C1-C10)-alkyl, (C3-C10)-cycloalkyl, (C1-C10)-alkenyl or (C1-C10)-alkynyl, each of which is optionally substituted with one, two or three groups selected from aryl, heteroaryl, heterocyclyl, —CO—(C1-C10)-alkyl, —CO-aryl, —CO-heteroaryl, —CO-heterocyclyl, —SO2—(C1-C10)-alkyl, —SO2-aryl SO2-heteroaryl, or —SO2-heterocyclyl;
• or
• R5 and R6 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, (C1-C5)-alkyl, (C3-C6)-cycloalkyl, (C1-C5)-alkenyl, (C1-C5)-alkynyl, (C1-C3)-hydroxyalkyl, (C1-C3)-alkyl-O—(C1-C4)-alkyl, aryl, heteroaryl, —CF3, —OH, —O—(C1-C7)-alkyl, —O-aryl, —O-heteroaryl, —O—(C2-C4)-alkyl-O—(C1-C7)-alkyl, (C2-C3)-alkylenedioxy, —NR8R9, —CN, —CO—NH2, —CO—NH—(C1-C3)-alkyl, —CO—N((C1-C3)-alkyl)2, —COOH, —CO—O—(C1-C5)-alkyl, —CHO, CO—(C1-C5)-alkyl, —S(O)n—(C1-C4)-alkyl, —S(O)n—NH2, —S(O)n—NH—(C1-C3)-alkyl, —S(O)n—N((C1-C3)-alkyl)2, oxo, —(CH2)m—NH2, —(CH2)m—NH—(C1-C4)-alkyl or
• —(CH2)m—N((C1-C4)-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 NR5;
• R7 is —OH, —O—(C1-C7)-alkyl, —NH2, —NH—(C1-C4)-alkyl, or
• —N((C1-C4)-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 NR5;
• R8 is hydrogen, or
• (C1-C7)-alkyl, (C3-C7)-cycloalkyl, (C1-C7)-alkenyl or (C1-C7)-alkynyl, each of which is optionally substituted with one, two or three groups selected from —OH, —O—(C1-C5)-alkyl, —NH2, —NH—(C1-C4)-alkyl and —N((C1-C4)-alkyl)2;
• R9 is hydrogen, —CO—(C1-C4)-alkyl, or
• (C1-C7)-alkyl, (C3-C7)-cycloalkyl, (C1-C7)-alkenyl or (C1-C7)-alkynyl, each of which is optionally substituted with one, two or three groups selected from —OH, —O—(C1-C5)-alkyl, —NH2, —NH—(C1-C4)-alkyl and —N((C1-C4)-alkyl)2;
• n is 0, 1, or 2;
• and
• m is 2, 3, or 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:

• 18
• or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof wherein
• R2 is —NR5R6, or
• aryl, heteroaryl, heterocyclyl, (C1-C10)-alkyl, (C3-C10)-cycloalkyl, (C1-C10)-alkenyl or (C1-C10)-alkynyl, each of which may be optionally substituted with one, two or three groups selected from halogen, —OH, aryl, heteroaryl, —O—(C1-C10)-alkyl, —O—(C1-C7)-alkyl-R7, —O-aryl, —O-heteroaryl, —SH, —S—(C1-C10)-alkyl, —S—(C1-C7)-alkyl-R7, —S-aryl, —S-heteroaryl, —P(O)(O—(C1-C5)-alkyl)2, —P(O)(OH)2, —CN, —NR8R9, —CO—NH2, —CO—NH—(C1-C3)-alkyl, —CO—N((C1-C3)-alkyl)2, —COOH, —CO—O—(C1-C5)-alkyl, heterocyclyl, and oxo;
• R3 is one, two or three substituents independently selected from hydrogen, halogen, —CF3, —OH, —O—(C1-C10)-alkyl, —O—(C1-C7)-alkyl-R7, —O-aryl, —O-heteroaryl, —SH, —S—(C1-C10)-alkyl, —S—(C1-C7)-alkyl-R7, —S-aryl, —S-heteroaryl, (C1-C3)-alkylene dioxy, —CN, —NO2, —NR8R9, —CONR5R6, —COOH, —CO—O—(C1-C5)-alkyl, heterocyclyl, —S(O)n—(C1-C7)-alkyl, —S(O)n-aryl, —S(O)n-heteroaryl, —S(O)n—NR5R6, or
• (C1-C7)-alkyl, (C3-C7)-cycloalkyl, (C1-C7)-alkenyl or (C1-C7)-alkynyl, each of which is optionally substituted with up to five groups independently selected from halogen, —OH, aryl, heteroaryl, —O—(C1-C10)-alkyl, —O—(C1-C7)-alkyl-R7, —O-aryl, —O-heteroaryl, —SH, —S—(C1-C10)-alkyl, —S—(C1-C7)-alkyl-R7, —S-aryl, —S-heteroaryl, —P(O)(O—(C1-C5)-alkyl)2, —P(O)(OH)2, —CN, —NR8NR9, —CO—NH2, —CO—NH—(C1-C3)-alkyl, —CO—N((C1-C3)-alkyl)2, —COOH, —CO—O—(C1-C5)-alkyl, heterocyclyl, and oxo;
• R5 and R6 independently are hydrogen, or
• (C1-C10)-alkyl, (C3-C10)-cycloalkyl, (C1-C10)-alkenyl or (C1-C10)-alkynyl, each of which is optionally substituted with one, two or three groups selected from aryl, heteroaryl, heterocyclyl, —CO—(C1-C10)-alkyl, —CO-aryl, —CO-heteroaryl, —CO-heterocyclyl, —SO2—(C1-C10)-alkyl, —SO2-aryl —SO2-heteroaryl, or —SO2-heterocyclyl;
• or
• R5 and R6 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, (C1-C5)-alkyl, (C3-C6)-cycloalkyl, (C1-C5)-alkenyl, (C1-C5)-alkynyl, (C1-C3)-hydroxyalkyl, (C1-C3)-alkyl-O—(C1-C4)-alkyl, aryl, heteroaryl, —CF3, —OH, —O—(C1-C7)-alkyl, —O-aryl, —O-heteroaryl, —O—(C2-C4)-alkyl-O—(C1-C7)-alkyl, (C2-C3)-alkylenedioxy, —NR8R9, —CN, —CO—NH2, —CO—NH—(C1-C3)-alkyl, —CO—N((C1-C3)-alkyl)2, —COOH, —CO—O—(C1-C5)-alkyl, —CHO, CO—(C1-C5)-alkyl, —S(O)n—(C1-C4)-alkyl, —S(O)n—NH2, —S(O)n—NH—(C1-C3)-alkyl, —S(O)n—N((C1-C3)-alkyl)2, oxo, —(CH2)m—NH2, —(CH2)m—NH—(C1-C4)-alkyl or
• —(CH2)m—N((C1-C4)-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 NR5;
• R7 is —OH, —O—(C1-C7)-alkyl, —NH2, —NH—(C1-C4)-alkyl, or
• —N((C1-C4)-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 NR5;
• R8 is hydrogen, or
• (C1-C7)-alkyl, (C3-C7)-cycloalkyl, (C1-C7)-alkenyl or (C1-C7)-alkynyl, each of which is optionally substituted with one, two or three groups selected from —OH, —O—(C1-C5)-alkyl, —NH2, —NH—(C1-C4)-alkyl and —N((C1-C4)-alkyl)2;
• R9 is hydrogen, —CO—(C1-C4)-alkyl, or
• (C1-C7)-alkyl, (C3-C7)-cycloalkyl, (C1-C7)-alkenyl or (C1-C7)-alkynyl, each of which is optionally substituted with one, two or three groups selected from —OH, —O—(C1-C5)-alkyl, —NH2, —NH—(C1-C4)-alkyl and —N((C1-C4)-alkyl)2;
• n is 0, 1, or 2;
• and
• m is 2, 3, or 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:

• 19
• or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof wherein
• A1 is aryl or heteroaryl, each of which may be optionally substituted with one, two or three groups independently selected from halogen, aryl, —CF3, —NO2, —OH, —O—(C1-C7)-alkyl, —O—(C2-C4)-alkyl-O—(C1-C7)-alkyl, —O-aryl, (C1-C2)-alkylenedioxy, —NR5R6, —CN, —CO—NR5R6, —COOH, —CO—O—(C1-C5)-alkyl, heterocyclyl, —CHO, —CO—(C1-C10)-alkyl, —CO-aryl, —CO-heteroaryl, or
• (C1-C10)-alkyl, (C3-C10)-cycloalkyl, (C1-C10)-alkenyl or (C1-C10)-alkynyl, each of which is optionally substituted with up to five groups independently selected from halogen, —OH, aryl, heteroaryl, —O—(C1-C10)-alkyl, —O—(C1-C7)-alkyl-R7, —O-aryl, —O-heteroaryl, —SH, —S—(C1-C10)-alkyl, —S—(C1-C7)-alkyl-R7, —S-aryl, —S-heteroaryl, —P(O)(O—(C1-C5)-alkyl)2, —P(O)(OH)2, —CN, —NR8R9, —CO—NH2, —CO—NH—(C1-C3)-alkyl, —CO—N((C1-C3)-alkyl)2, —COOH, —CO—O—(C1-C5)-alkyl, heterocyclyl, and oxo;
• R2 is —NR5R6, or
• aryl, heteroaryl, heterocyclyl, (C1-C10)-alkyl, (C3-C10)-cycloalkyl, (C1-C10)-alkenyl or (C1-C10)-alkynyl, each of which may be optionally substituted with one, two or three groups selected from halogen, —OH, aryl, heteroaryl, —O—(C1-C10)-alkyl, —O—(C1-C7)-alkyl-R7, —O-aryl, —O-heteroaryl, —SH, —S—(C1-C10)-alkyl, —S—(C1-C7)-alkyl-R7, —S-aryl, —S-heteroaryl, —P(O)(O—(C1-C5)-alkyl)2, —P(O)(OH)2, —CN, —NR8R9, —CO—NH2, —CO—NH—(C1-C3)-alkyl, —CO—N((C1-C3)-alkyl)2, —COOH, —CO—O—(C1-C5)-alkyl, heterocyclyl, and oxo;
• R3 is one, two or three substituents independently selected from hydrogen, halogen, —CF3, —OH, —O—(C1-C10)-alkyl, —O—(C1-C7)-alkyl-R7, —O-aryl, —O-heteroaryl, —SH, —S—(C1-C10)-alkyl, —S—(C1-C7)-alkyl-R7, —S-aryl, —S-heteroaryl, (C1-C3)-alkylene dioxy, —CN, —NO2, —NR8R9, —CONR5R6, —COOH, —CO—O—(C1-C5)-alkyl, heterocyclyl, —S(O)n—(C1-C7)-alkyl, —S(O)n-aryl, —S(O)n-heteroaryl, —S(O)n—NR5R6, or
• (C1-C7)-alkyl, (C3-C7)-cycloalkyl, (C1-C7)-alkenyl or (C1-C7)-alkynyl, each of which is optionally substituted with up to five groups independently selected from halogen, —OH, aryl, heteroaryl, —O—(C1-C10)-alkyl, —O—(C1-C7)-alkyl-R7, —O-aryl, —O-heteroaryl, —SH, —S—(C1-C10)-alkyl, —S—(C1-C7)-alkyl-R7, —S-aryl, —S-heteroaryl, —P(O)(O—(C1-C5)-alkyl)2, —P(O)(OH)2, —CN, —NR8R9, —CO—NH2, —CO—NH—(C1-C3)-alkyl, —CO—N((C1-C3)-alkyl)2, —COOH, —CO—O—(C1-C5)-alkyl, heterocyclyl, and oxo;
• R5 and R6 independently are hydrogen, or
• (C1-C10)-alkyl, (C3-C10)-cycloalkyl, (C1-C10)-alkenyl or (C1-C10)-alkynyl, each of which is optionally substituted with one, two or three groups selected from aryl, heteroaryl, heterocyclyl, —CO—(C1-C10)-alkyl, —CO-aryl, —CO-heteroaryl, —CO-heterocyclyl, —SO2—(C1-C10)-alkyl, —SO2-aryl —SO2-heteroaryl, or —SO2-heterocyclyl;
• or
• R5 and R6 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, (C1-C5)-alkyl, (C3-C6)-cycloalkyl, (C1-C5)-alkenyl, (C1-C5)-alkynyl, (C1-C3)-hydroxyalkyl, (C1-C3)-alkyl-O—(C1-C4)-alkyl, aryl, heteroaryl, —CF3, —OH, —O—(C1-C7)-alkyl, —O-aryl, —O-heteroaryl, —O—(C2-C4)-alkyl-O—(C1-C7)-alkyl, (C2-C3)-alkylenedioxy, —NR8R9, —CN, —CO—NH2, —CO—NH—(C1-C3)-alkyl, —CO—N((C1-C3)-alkyl)2, —COOH, —CO—O—(C1-C5)-alkyl, —CHO, CO—(C1-C5)-alkyl, —S(O)n—(C1-C4)-alkyl, —S(O)n—NH2, —S(O)n—NH—(C1-C3)-alkyl, —S(O)n—N((C1-C3)-alkyl)2, oxo, —(CH2)m—NH2, —(CH2)m—NH—(C1-C4)-alkyl or
• —(CH2)m—N((C1-C4)-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 NR5;
• R7 is —OH, —O—(C1-C7)-alkyl, —NH2, —NH—(C1-C4)-alkyl, or —N((C1-C4)-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 NR5;
• R8 is hydrogen, or
• (C1-C7)-alkyl, (C3-C7)-cycloalkyl, (C1-C7)-alkenyl or (C1-C7)-alkynyl, each of which is optionally substituted with one, two or three groups selected from —OH, —O—(C1-C5)-alkyl, —NH2, —NH—(C1-C4)-alkyl and —N((C1-C4)-alkyl)2;
• R9 is hydrogen, —CO—(C1-C4)-alkyl, or
• (C1-C7)-alkyl, (C3-C7)-cycloalkyl, (C1-C7)-alkenyl or (C1-C7)-alkynyl, each of which is optionally substituted with one, two or three groups selected from —OH, —O—(C1-C5)-alkyl, —NH2, —NH—(C1-C4)-alkyl and —N((C1-C4)-alkyl)2;
• n is 0, 1, or 2;
• and
• m is 2, 3, or 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:

• 20
• or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof wherein
• A1 is aryl or heteroaryl, each of which may be optionally substituted with one, two or three groups independently selected from halogen, aryl, —CF3, —NO2, —OH, —O—(C1-C7)-alkyl, —O—(C2-C4)-alkyl-O—(C1-C7)-alkyl, —O-aryl, (C1-C2)-alkylenedioxy, —NR5R6, —CN, —CO—NR5R6, —COOH, —CO—O—(C1-C5)-alkyl, heterocyclyl, —CHO, —CO—(C1-C10)-alkyl, —CO-aryl, —CO-heteroaryl, or
• (C1-C10)-alkyl, (C3-C10)-cycloalkyl, (C1-C10)-alkenyl or (C1-C10)-alkynyl, each of which is optionally substituted with up to five groups independently selected from halogen, —OH, aryl, heteroaryl, —O—(C1-C10)-alkyl, —O—(C1-C7)-alkyl-R7, —O-aryl, —O-heteroaryl, —SH, —S—(C1-C10)-alkyl, —S—(C1-C7)—alkyl-R7, —S-aryl, —S-heteroaryl, —P(O)(O—(C1-C5)-alkyl)2, —P(O)(OH)2, —CN, —NR8R9, —CO—NH2, —CO—NH—(C1-C3)-alkyl, —CO—N((C1-C3)-alkyl)2, —COOH, —CO—O—(C1-C5)-alkyl, heterocyclyl, and oxo;
• A2 represents a ringed structure consisting of aryl, heterocyclyl, heteroaryl or (C3-C10)-cycloalkyl;
• R3 is one, two or three substituents independently selected from hydrogen, halogen, —CF3, —OH, —O—(C1-C10)-alkyl, —O—(C1-C7)-alkyl-R7, —O-aryl, —O-heteroaryl, —SH, —S—(C1-C10)-alkyl, —S—(C1-C7)-alkyl-R7, —S-aryl, —S-heteroaryl, (C1-C3)-alkylene dioxy, —CN, —NO2, —NR8R9, —CONR5R6, —COOH, —CO—O—(C1-C5)-alkyl, heterocyclyl, —S(O)n—(C1-C7)-alkyl, —S(O)n-aryl, —S(O)n-heteroaryl, —S(O)n—NR5R6, or
• (C1-C7)-alkyl, (C3-C7)-cycloalkyl, (C1-C7)-alkenyl or (C1-C7)-alkynyl, each of which is optionally substituted with up to five groups independently selected from halogen, —OH, aryl, heteroaryl, —O—(C1-C10)-alkyl, —O—(C1-C7)-alkyl-R7, —O-aryl, —O-heteroaryl, —SH, —S—(C1-C10)-alkyl, —S—(C1-C7)-alkyl-R7, —S-aryl, —S-heteroaryl, —P(O)(O—(C1-C5)-alkyl)2, —P(O)(OH)2, —CN, —NR8R9, —CO—NH2, —CO—NH—(C1-C3)-alkyl, —CO—N((C1-C3)-alkyl)2, —COOH, —CO—O—(C1-C5)-alkyl, heterocyclyl, and oxo;
• R5 and R6 independently are hydrogen, or
• (C1-C10)-alkyl, (C3-C10)-cycloalkyl, (C1-C10)-alkenyl or (C1-C10)-alkynyl, each of which is optionally substituted with one, two or three groups selected from aryl, heteroaryl, heterocyclyl, —CO—(C1-C10)-alkyl, —CO-aryl, —CO-heteroaryl, —CO-heterocyclyl, —SO2—(C1-C10)-alkyl, —SO2-aryl —SO2-heteroaryl, or —SO2-heterocyclyl;
• or
• R5 and R6 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, (C1-C5)-alkyl, (C3-C6)-cycloalkyl, (C1-C5)-alkenyl, (C1-C5)-alkynyl, (C1-C3)-hydroxyalkyl, (C1-C3)-alkyl-O—(C1-C4)-alkyl, aryl, heteroaryl, —CF3, —OH, —O—(C1-C7)-alkyl, —O-aryl, —O-heteroaryl, —O—(C2-C4)-alkyl-O—(C1-C7)-alkyl, (C2-C3)-alkylenedioxy, —NR8R9, —CN, —CO—NH2, —CO—NH—(C1-C3)-alkyl, —CO—N((C1-C3)-alkyl)2, —COOH, —CO—O—(C1-C5)-alkyl, —CHO, CO—(C1-C5)-alkyl, —S(O)n—(C1-C4)-alkyl, —S(O)n—NH2, —S(O)n—NH—(C1-C3)-alkyl, —S(O)n—N((C1-C3)-alkyl)2, oxo, —(CH2)m—NH2, —(CH2)m—NH—(C1-C4)-alkyl or
• —(CH2)m—N((C1-C4)-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 NR5;
• R7 is —OH, —O—(C1-C7)-alkyl, —NH2, —NH—(C1-C4)-alkyl, or
• —N((C1-C4)-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 NR5;
• R8 is hydrogen, or
• (C1-C7)-alkyl, (C3-C7)-cycloalkyl, (C1-C7)-alkenyl or (C1-C7)-alkynyl, each of which is optionally substituted with one, two or three groups selected from —OH, —O—(C1-C5)-alkyl, —NH2, —NH—(C1-C4)-alkyl and —N((C1-C4)-alkyl)2;
• R9 is hydrogen, —CO—(C1-C4)-alkyl, or
• (C1-C7)-alkyl, (C3-C7)-cycloalkyl, (C1-C7)-alkenyl or (C1-C7)-alkynyl, each of which is optionally substituted with one, two or three groups selected from —OH, —O—(C1-C5)-alkyl, —NH2, —NH—(C1-C4)-alkyl and —N((C1-C4)-alkyl)2;
• n is 0, 1, or 2;
• and
• m is 2, 3, or 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:

• 21
• or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof wherein
• A1 is aryl or heteroaryl, each of which may be optionally substituted with one, two or three groups independently selected from halogen, aryl, —CF3, —NO2, —OH, —O—(C1-C7)-alkyl, —O—(C2-C4)-alkyl-O—(C1-C7)-alkyl, —O-aryl, (C1-C2)-alkylenedioxy, —NR5R6, —CN, —CO—NR5R6, —COOH, —CO—O—(C1-C5)-alkyl, heterocyclyl, —CHO, —CO—(C1-C10)-alkyl, —CO-aryl, —CO-heteroaryl, or
• (C1-C10)-alkyl, (C3-C10)-cycloalkyl, (C1-C10)-alkenyl or (C1-C10)-alkynyl, each of which is optionally substituted with up to five groups independently selected from halogen, —OH, aryl, heteroaryl, —O—(C1-C10)-alkyl, —O—(C1-C7)-alkyl-R7, —O-aryl, —O-heteroaryl, —SH, —S—(C1-C10)-alkyl, —S—(C1-C7)-alkyl-R7, —S-aryl, —S-heteroaryl, —P(O)(O—(C1-C5)-alkyl)2, —P(O)(OH)2, —CN, —NR8R9, —CO—NH2, —CO—NH—(C1-C3)-alkyl, —CO—N((C1-C3)-alkyl)2, —COOH, —CO—O—(C1-C5)-alkyl, heterocyclyl, and oxo;
• A2 represents a ringed structure consisting of aryl, heteroaryl, heterocyclyl or (C3-C10)-cycloalkyl;
• R2 is —NR5R6, or
• aryl, heteroaryl, heterocyclyl, (C1-C10)-alkyl, (C3-C10)-cycloalkyl, (C1-C10)-alkenyl or (C1-C10)-alkynyl, each of which may be optionally substituted with one, two or three groups selected from halogen, —OH, aryl, heteroaryl, —O—(C1-C10)-alkyl, —O—(C1-C7)-alkyl-R7, —O-aryl, —O-heteroaryl, —SH, —S—(C1-C10)-alkyl, —S—(C1-C7)-alkyl-R7, —S-aryl, —S-heteroaryl, —P(O)(O—(C1-C5)-alkyl)2, —P(O)(OH)2, —CN, —NR8R9, —CO—NH2, —CO—NH—(C1-C3)-alkyl, —CO—N((C1-C3)-alkyl)2, —COOH, —CO—O—(C1-C5)-alkyl, heterocyclyl, and oxo;
• R3 is one, two or three substituents independently selected from hydrogen, halogen, —CF3, —OH, —O—(C1-C10)-alkyl, —O—(C1-C7)-alkyl-R7, —O-aryl, —O-heteroaryl, —SH, —S—(C1-C10)-alkyl, —S—(C1-C7)-alkyl-R7, —S-aryl, —S-heteroaryl, (C1-C3)-alkylene dioxy, —CN, —NO2, —NR8R9, —CONR5R6, —COOH, —CO—O—(C1-C5)-alkyl, heterocyclyl, —S(O)n—(C1-C7)-alkyl, —S(O)n-aryl, —S(O)n-heteroaryl, —S(O)n—NR5R6, or
• (C1-C7)-alkyl, (C3-C7)-cycloalkyl, (C1-C7)-alkenyl or (C1-C7)-alkynyl, each of which is optionally substituted with up to five groups independently selected from halogen, —OH, aryl, heteroaryl, —O—(C1-C10)-alkyl, —O—(C1-C7)-alkyl-R7, —O-aryl, —O-heteroaryl, —SH, —S—(C1-C10)-alkyl, —S—(C1-C7)-alkyl-R7, —S-aryl, —S-heteroaryl, —P(O)(O—(C1-C5)-alkyl)2, —P(O)(OH)2, —CN, —NR8R9, —CO—NH2, —CO—NH—(C1-C3)-alkyl, —CO—N((C1-C3)-alkyl)2, —COOH, —CO—O—(C1-C5)-alkyl, heterocyclyl, and oxo;
• R5 and R6 independently are hydrogen, or
• (C1-C10)-alkyl, (C3-C10)-cycloalkyl, (C1-C10)-alkenyl or (C1-C10)-alkynyl, each of which is optionally substituted with one, two or three groups selected from aryl, heteroaryl, heterocyclyl, —CO—(C1-C10)-alkyl, —CO-aryl, —CO-heteroaryl, —CO-heterocyclyl, —SO2—(C1-C10)-alkyl, —SO2-aryl —SO2-heteroaryl, or —SO2-heterocyclyl;
• or
• R5 and R6 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, (C1-C5)-alkyl, (C3-C6)-cycloalkyl, (C1-C5)-alkenyl, (C1-C5)-alkynyl, (C1-C3)-hydroxyalkyl, (C1-C3)-alkyl-O—(C1-C4)-alkyl, aryl, heteroaryl, —CF3, —OH, —O—(C1-C7)-alkyl, —O-aryl, —O-heteroaryl, —O—(C2-C4)-alkyl-O—(C1-C7)-alkyl, (C2-C3)-alkylenedioxy, —NR8R9, —CN, —CO—NH2, —CO—NH—(C1-C3)-alkyl, —CO—N((C1-C3)-alkyl)2, —COOH, —CO—O—(C1-C5)-alkyl, —CHO, CO—(C1-C5)-alkyl, —S(O)n—(C1-C4)-alkyl, —S(O)n—NH2, —S(O)n—NH—(C1-C3)-alkyl, —S(O)n—N((C1-C3)-alkyl)2, oxo, —(CH2)m—NH2, —(CH2)m—NH—(C1-C4)-alkyl or
• —(CH2)m—N((C1-C4)-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 NR5;
• R7 is —OH, —O—(C1-C7)-alkyl, —NH2, —NH—(C1-C4)-alkyl, or
• —N((C1-C4)-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 NR5;
• R8 is hydrogen, or
• (C1-C7)-alkyl, (C3-C7)-cycloalkyl, (C1-C7)-alkenyl or (C1-C7)-alkynyl, each of which is optionally substituted with one, two or three groups selected from —OH, —O—(C1-C5)-alkyl, —NH2, —NH—(C1-C4)-alkyl and —N((C1-C4)-alkyl)2;
• R9 is hydrogen, —CO—(C1-C4)-alkyl, or
• (C1-C7)-alkyl, (C3-C7)-cycloalkyl, (C1-C7)-alkenyl or (C1-C7)-alkynyl, each of which is optionally substituted with one, two or three groups selected from —OH, —O—(C1-C5)-alkyl, —NH2, —NH—(C1-C4)-alkyl and —N((C1-C4)-alkyl)2;
• n is 0, 1, or 2;
• and
• m is 2, 3, or 4.