Substituted 1,4-dihydroindeno1,2-cpyrazoles useful as inhibitors of tyrosine kinase

摘要

A 1,4-dihydroindeno[1,2-c]pyrazole derivatives or pharmaceutically acceptable salts thereof has the formula (I) wherein: L1 is (E)2(CH2)q with the alkylene chain (CH2)q being optionally substituted; E is NR24. O or S; s is 0 or 1 and q is 0 to 6, provided that when s is 1 q is at least 1; A is CONH, NHCO, SO2NH, NHSO2, or NR25; L2 is (CH2)r which can be optionally substituted; r is 0 to 6; R2 is optionally substituted alkyl, amino or alkoxy or halo, hydroxy, cyano, nitro, carbamoyl, alkanoyl or alkoxycarbonyl; n is 0, 1, 2 or 3; X is substituted methylene, carbonyl, oxygen, C=NOR7, NR8, (CH2)n' or S(O)p; p is 0, 1 or 2; R7 is H or alkyl; R8 is H or optionally substituted alkyl or phenyl; n' is 1, 2 or 3, R3 to R6 are independently H, halo, optionally substituted alkyl, alkenyl, alkynyl, phenyl alkyl, phenyl alkoxy, amino, alkoxy or phenoxy, hydroxy, CORa, alkanoyl, nitro, cyano, Ra is hydroxy, alkoxy or optionally substituted amino; a) when A is SO2NH, or NHSO2 R1 is alkoxy, amino, optionally substituted phenyl, heteroaryl or a five, six or seven membered saturated heterocyclic ring containing a nitrogen atom which optionally contains an additional hetero atom selected from O, S or N or b) when A is CONH or NHCO R1 is substituted phenyl or optionally substituted heteroaryl or a five, six or seven membered saturated heterocyclic ring containing a nitrogen atom which optionally contains an additional hetero atom selected from O, S or N or c) when A is a group NR25 and q is at least 1 then R1 is optionally substituted phenyl, heteroaryl or amino or d) when A is a group NR25 and q is 0 and s is 0 then R1 is optionally substituted heteroaryl; R24 and R25 are as defined in the specification provided that no two heteroatoms are attached to the same sp3 hybridized carbon atom. The compounds are useful for treating burns, chronic lung disease, stroke, polyps, psoriasis, allergic inflammation, macular degeneration, diabetic retinopathy, ovarian hyperstimulation syndrome or brain tumor-associated cerebral edema.