New (heterocyclyl- pyrimidino or -pyrido)fused pyrimidine derivatives

摘要

4-Amino-substituted fused pyrimidine compounds of formula (I) and their tautomers, stereoisomers and salts are new. Ra = H or Me; Rb = Ph or Ph-alkyl (both optionally ring-substituted by R1-R3); R1 = H, F, Cl, Br, I, alkyl, CF3, ethenyl, ethinyl, alkoxy, 3-6C cycloalkyl, OCF3, CN, NH2, alkylamino, dialkylamino or NO2; R2 = H, F, Cl, Br or alkyl; R3 = H, F, Cl or Br; A+B = -N=CRc-CH=CH-, -CH=N-CRc=CH-, -CH=CRc-N=CH-, -CH=CH-CRc=N- or -CH=N-CRc=N-; Rc = morpholino, 1-piperazinyl or 3-oxo-1-piperazinyl (all optionally mono- or di-substituted by alkyl), 1-piperazinyl (substituted in the 4 position by 3-6C cycloalkyl, 3-tetrahydrofuranyl, 4-tetrahydropyranyl, 3-pyrrolidinyl, 1-alkyl-3-pyrrolidinyl, 3- or 4- piperidinyl, or 1-alkyl-(3 or 4)-piperidinyl), R4-substituted Het, or Het' with two H replaced by n-alkylene (optionally with one CH2 replaced by O, imino or N-alkylimino), to form a bridge; or Rc = NR5R6; Het' = 1-azetidinyl (with a 4-5C bridge at the 3 position), or 1-pyrrolidinyl or 1-piperidinyl (in both, the bridge is bonded to carbon, and has 3-5C with the ends on the same C, 3-4C with the ends on neighbouring C atoms, 2-3C when the ends are separated by another atom, or (for piperidinyl) 1-2C when the ends are separated by two atoms); Het = 1-azetidinyl, 1-pyrrolidinyl, 1-piperidinyl or 1-azacyclohept-1-yl; R4 = OH, alkoxy, amino, dialkylamino, alkylamino, alkylcarbonylamino, N-alkyl-alkylcarbonylamino, 2-oxo-1-pyrrolidinyl, 2-oxo-1-piperidinyl, alkoxycarbonylamino, N-alkyl- alkoxycarbonylamino, alkylsulphonylamino, N-alkyl-alkylsulphonylamino, 3-6C cycloalkyl, tetrahydrofuranyl, tetrahydropyranyl, pyrrolidinyl, 1-alkyl-pyrrolidinyl, piperidinyl, 1-alkyl-piperidinyl, morpholino, 1-piperazinyl, 4-alkyl-1-piperazinyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, 1-pyrrolidinylcarbonyl, 1-piperidinylcarbonyl, morpholinocarbonyl, 1-piperazinylcarbonyl, 4-alkyl-1-piperazinylcarbonyl or CN; R5 = H or alkyl; and R6 = 3-pyrrolidinyl, 3- or 4-piperidinyl (all with the ring N optionally substituted by alkyl, alkylcarbonyl, alkylsulphonyl, alkoxycarbonyl, 3-6C cycloalkyl, 3-tetrahydrofuranyl, 3- or 4-tetrahydropyranyl, 3-pyrrolidinyl, 1-alkyl-3-pyrrolidinyl, 3- or 4-piperidinyl, or 1-alkyl-(3 or r)-piperidinyl), 3- or 4-quinuclidinyl, 3-tropanyl, desmethyl-3-tropanyl, 3-tetrahydrofuranyl, 3- or 4-tetrahydropyranyl, R4-substituted 5-7C cycloalkyl, or R4-substituted 2-6C alkyl; alkyl = 1-4C alkyl unless stated otherwise. The compound 4-(3-bromophenyl)amino-6-(1-piperidinyl)pyrido3,4-dpyrimidine is excluded.