Patent ID: 6486185
Filing Date: 2002-11-26
Classification: A61P,C07D

Abstract:
A 3-heteroarylidene-2-indolinone having the chemical structure: or a physiologically acceptable salt or prodrug thereof wherein,A, B, D and E are selected from the group consisting of carbon and nitrogen, it being understood that the nitrogen-containing 9-member bicyclic ring formed is one known in the chemical arts; it being further understood that when A, B, D, or E is nitrogen, R3, R4, R5 or R6, respectively, does not exist; R1 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, hydroxy, alkoxy, carboxyl, C-amido and sulfonyl; R2 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, and heteroalicyclic; R3, R4, R5 and R6 are independently selected from the group consisting of hydrogen, alkyl, trihaloalkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, hydroxy, alkoxy, aryloxy, â€”SH, â€”S-alkyl, â€”S-cycloalkyl, â€”S-aryl, â€”S-heteroaryl, sulfinyl, sulfonyl, sulfonamido, carbonyl, carboxyl, cyano, nitro, halo, â€”OC(O)NR10R11, N-carbamyl, â€”OC(S)NR10R11, N-thiocarbamyl, C-amido, N-amido, amino and â€”NR10R11; R10 and R11 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; R3 and R4, R4 and R5, or R4 and R5 may combine to form a six-member aryl or heteroaryl ring; Q is a heteroaryl group having the following structure: J is selected from the group consisting of oxygen, nitrogen and sulfur; K, L and M are independently selected from the group consisting of carbon, nitrogen, oxygen and sulfur such that the five-member heteroaryl ring formed is one known in the chemical arts, it being understood that when K, L and M are nitrogen, sulfur or oxygen, R8 or -(alk1)nZ cannot be covalently bonded to that atom; when J is nitrogen, R7 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, hydroxy, alkoxy, aryloxy, carbonyl, carboxyl, C-amido, guanyl and sulfonyl and when J is oxygen or sulfur, R7 does not exist and there is no bond; R8 is selected from the group consisting of hydrogen, alkyl, trihaloalkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, hydroxy, alkoxy, aryloxy, â€”SH, â€”S-alkyl, â€”S-cycloalkyl, â€”S-aryl, â€”S-heteroaryl, sulfinyl, sulfonyl, sulfonamido, carbonyl, carboxyl, cyano, nitro, halo, â€”OC(O)NR10R11, N-carbamyl, â€”OC(S)NR10R11 N-thiocarbamyl, C-amido, N-amido, amino, â€”NR10R11, trihalomethyl, a five member cycloalkyl, aryl, heteroaryl or heteroalicyclic ring fused to two adjacent atoms of the Q ring; and a six-member cycloalkyl, aryl, heteroaryl, or heteroalicyclic ring fused to two adjacent atoms of the Q ring; R10 and R11 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; alk1 is selected from the group consisting of optionally substituted methylene (â€”CRRâ€²â€”), optionally substituted ethylene (â€”C(R)&boxH;C(Râ€²)â€”) and acetylene (â€”Câ‰¡Câ€”); R and Râ€² are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, alkoxy, â€”S-alkyl, â€”S-cycloalkyl, aryloxy and halo; n is 0 to 10, inclusive with the proviso that when n is 0, R7 is not alkyl substituted with aryl; and Z is a polar group selected from the group consisting of hydroxy, alkoxy, carboxy, nitro, cyano, carbamyl, amino, quaternary ammonium, amido, ureido, sulfonamido, sulfinyl, sulfonyl, phosphono, phosphonyl, morpholino, piperazinyl and tetrazolo.