New 2-(((hetero)aryl-alkyl)-amino)-aza-benzamide derivatives, are VEGF receptor, KDR kinase and FLT kinase inhibitors useful e.g. for treating tumors, psoriasis, arthritis or renal or ophthalmological diseases

摘要

N-Substituted 2-((aryl- or heteroaryl-alkyl)-amino)-mono- or polyaza-benzamide derivatives (I) are new. Also new are 6 specific intermediate compounds. Heterocyclic amine derivatives of formula (I) and their isomers and salts are new. W = O, S, H2 or NR8; Z' = direct bond, NR10, N, optionally branched 1-12C alkylene or -(CRaRb)m-(CRcRd)n-(CReRf)o-; m, n, o = 0-3; Ra - Rf = H, F, 1-4C alkyl or NR10; or Ra and/or Rb plus Rc and/or Rd or Rc or Rd plus Re and/or Rf may form a bond; or 1 or 2 of Ra - Rf may form a bridge of up to 3C to R1 or R7; R1 = 1-12C alkyl, 2-12C alkenyl, 3-10C cycloalkyl or 3-10C cycloalkenyl (all optionally substituted by one or more halo, OH, OT, aralkoxy, T and/or NR11R12); or aryl or heteroaryl (both optionally substituted by one or more of halo, OH, OT, aralkoxy and/or T (itself optionally substituted by one or more halo)); X = 1-6C alkylene; R2 = mono- or bicyclic aryl or heteroaryl (both optionally substituted by one or more of halo, T, OT and/or OH); A1 - A4 = N or C-R3, provided that (i) if A1 = N then A2 - A4 are not all C-R3 and (ii) A1 - A-4 are not all C-R3; R3 = H or halo; or OT, T or (1-6C) carboxyalkyl (all optionally substituted by one or more halo); R7 = H or T; or forms an up to 3 membered bridge to Ra - Rf or R1; R8 - R12 = H or T: or NR11R12 = ring (optionally containing a further heteroatom); and T = 1-6C alkyl. An Independent claim is included for the following new intermediates: (1) methyl 3-aminopyridine-2-carboxylate; (2) N-(isoquinolin-3-yl)-3-aminopyridine-2-carboxamide; (3) methyl 4-((4-pyridyl)-methyl)-amino-pyrimidine-5-carboxylate; (4) methyl 3-((4-pyridyl)-methyl)-amino-pyrimidine-5-carboxylate; (5) methyl 3-pyridylmethylamino-pyridine-2-carboxylate; and (6) 3-pyridylmethylamino-pyridine-2-carboxylic acid.