1h-Indazole-3-carboxamide compounds as cyclin dependent kinase (cdk) inhibitors

摘要

The invention provides a compound of the formula (I) for use in the prophylaxis or treatment of a disease state or condition mediated by a cyclin dependent kinase: wherein A is a group R² or CH₂-R² where R² is a carbocyclic or heterocyclic group having from 3 to 12 ring members; B is a bond or an acyclic linker group having a linking chain length of up to 3 atoms selected from C, N, S and O; R¹ is hydrogen or a group selected from SO₂R^b, SO₂NR⁷R⁸, CONR⁷R⁸, NR⁷R⁹ and carbocyclic and heterocyclic groups having from 3 to 7 ring members; R³, R⁴, R⁵ and R⁶ are the same or different and are each selected from hydrogen, halogen, hydroxy, trifluoromethyl, cyano, nitro, carboxy, amino, carbocyclic and heterocyclic groups having from 3 to 12 ring members; a group R^a-R^b wherein R^a is a bond, O, CO, X¹C(X²), C(X²)X¹, X¹C(X²)X¹, S, SO, SO₂, NR^c, SO₂NR^c or NR^cSO₂; and R^b is selected from hydrogen, carbocyclic and heterocyclic groups having from 3 to 12 ring members, and a C_1-8 hydrocarbyl group optionally substituted by one or more substituents selected from hydroxy, oxo, halogen, cyano, nitro, amino, mono- or di-C_1-4 hydrocarbylamino, carbocyclic and heterocyclic groups having from 3 to 12 ring members and wherein one or more carbon atoms of the C_1-8 hydrocarbyl group may optionally be replaced by O, S, SO, SO₂, NR^c, X¹C(X²), C(X²)X¹ or X¹C(X²)X¹; R^c is hydrogen or C_1-4 hydrocarbyl; X¹ is O, S or NR^c and X² is -O, -S or -NR^c; R⁷ is selected from hydrogen and a C_1-8 hydrocarbyl group optionally substituted by one or more substituents selected from hydroxy, oxo, halogen, cyano, nitro, amino, mono- or di-C_1-4 hydrocarbylamino, carbocyclic and heterocyclic groups having from 3 to 12 ring members and wherein one or more carbon atoms of the C_1-8 hydrocarbyl group may optionally be replaced by O, S, SO, SO₂, NR^c, X¹C(X²), C(X²)X¹ or X¹C(X²)X¹; R⁸ is selected from R⁷ and carbocyclic and heterocyclic groups having from 3 to 12 ring members; R⁹ is selected from R⁸, COR⁸ and SO₂R⁸; or NR⁷R⁸ or NR⁷R⁹ may each form a heterocyclic group having from 5 to 12 ring members; but excluding the compounds N-[(morpholin-4-yl)phenyl-1H-indazole-3-carboxamide and N-[4-(acetylaminosulphonyl)phenyl-1H-indazole-3-carboxamide.