US 2003/0158215 A1Published application

Tyrosine kinase inhibitors

AssigneeSugen, Inc.

InventorsPENG CHO TANG, LI SUN, GERALD MCMAHON

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Abstract

The present invention relates to novel 3-hetero-arylideneazaindolin-2-one compounds and physiologically acceptable salts and prodrugs thereof which are expected to modulate the activity of protein tyrosine kinases and therefore to be useful in the prevention and treatment of protein tyrosine kinase related cellular disorders such as cancer.

Claims36

Dependent claims

A 3-heteroarylideneazaindolin-2-one compound havin/the following chemical structure:

2
wherein,
A is selected from the group consisting of nitrogen, oxygen and sulfur and it is understood that when A is oxygen or sulfur, R3 does not exist and there is no bond;
B, D, E, F and G are independently selected from the group consisting of carbon and nitrogen but at least one of D, E, F and G must be nitrogen and it is understood that when B, D, E, F or G is nitrogen, R6, R7, R8, R9 and R10, respectively, do not exist and there is no bond;
Z is selected from the group consisting of oxygen, sulfur and NR11 wherein,
R11 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, hydroxy, alkoxy, aryloxy, carbonyl, C-carboxyl, O-carboxyl, C-amido, guanyl, sulfonyl and trihalomethanesulfonyl;
R1 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, hydroxy, alkoxy, trihalomethanecarbonyl, sulfonyl, trihalomethanesulfonyl, C-carboxyl, O-carboxyl, C-amido, and guanyl.
R2 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl and halogen;
When A is nitrogen,
R3 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, hydroxy, alkoxy, aryloxy, carbonyl, C-carboxyl, O-carboxyl, C-amido, guanyl, sulfonyl and trihalomethanesulfonyl;
R4, R5, R6, R7, R8, R9 and R10 are independently selected from the group consisting of hydrogen, alkyl, trihaloalkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, S-sulfonamido, N-Sulfonamido, trihalomethanesulfonyl, carbonyl, C-carboxyl, O-carboxyl, C-amido, N-amido, cyano, nitro, halo, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, guanyl, guanidino, ureido, amino and —NR12R13;
wherein
R12 and R13 are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, carbonyl, sulfonyl and, combined, a five- or six-member heteroalicyclic ring containing at least one nitrogen;
and,
R4 and R5 or R5 and R6 may combine to form a six-member cycloalkyl, aryl, heteroaryl or heteroalicyclic ring;
and the physiologically acceptable salt and prodrugs thereof.

13 more elements

Dependencies are inferred from the claim text.

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Abstract

A 3-heteroarylideneazaindolin-2-one compound havin/the following chemical structure:

2
wherein,
A is selected from the group consisting of nitrogen, oxygen and sulfur and it is understood that when A is oxygen or sulfur, R3 does not exist and there is no bond;
B, D, E, F and G are independently selected from the group consisting of carbon and nitrogen but at least one of D, E, F and G must be nitrogen and it is understood that when B, D, E, F or G is nitrogen, R6, R7, R8, R9 and R10, respectively, do not exist and there is no bond;
Z is selected from the group consisting of oxygen, sulfur and NR11 wherein,
R11 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, hydroxy, alkoxy, aryloxy, carbonyl, C-carboxyl, O-carboxyl, C-amido, guanyl, sulfonyl and trihalomethanesulfonyl;
R1 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, hydroxy, alkoxy, trihalomethanecarbonyl, sulfonyl, trihalomethanesulfonyl, C-carboxyl, O-carboxyl, C-amido, and guanyl.
R2 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl and halogen;
When A is nitrogen,
R3 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, hydroxy, alkoxy, aryloxy, carbonyl, C-carboxyl, O-carboxyl, C-amido, guanyl, sulfonyl and trihalomethanesulfonyl;
R4, R5, R6, R7, R8, R9 and R10 are independently selected from the group consisting of hydrogen, alkyl, trihaloalkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, S-sulfonamido, N-Sulfonamido, trihalomethanesulfonyl, carbonyl, C-carboxyl, O-carboxyl, C-amido, N-amido, cyano, nitro, halo, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, guanyl, guanidino, ureido, amino and —NR12R13;
wherein
R12 and R13 are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, carbonyl, sulfonyl and, combined, a five- or six-member heteroalicyclic ring containing at least one nitrogen;
and,
R4 and R5 or R5 and R6 may combine to form a six-member cycloalkyl, aryl, heteroaryl or heteroalicyclic ring;
and the physiologically acceptable salt and prodrugs thereof.

13 more elements