New anthranilamide derivatives and analogs containing heterocycle N-oxide group, as KDR/FLT tyrosine kinase inhibitors, used for e.g. treating psoriasis, restenosis, leukemia, arthritis, eye or kidney disease or arteriosclerosis

摘要

N-Substituted 2-(N-(N-oxido-heterocyclyl-alkyl)-amino)-benzamide derivatives (I) (including thioamide, amine or amidine analogs and/or mono- or poly-aza analogs) are new. Anthranilamide derivatives and analogs of formula (I) and their salts and isomers are new; W = O, S, H2 or NR8; Z = direct bond, -N(R10)-, =N-, optionally branched 1-12C alkylene or -(CRaRb)m-(CRcRd)n-(CReRf)p; m, n, p = 0-3; Ra - Rf = H, F, 1-4C alkyl or NR11; or Ra and/or Rb plus Rc and/or Rd or Rd plus Re and/or Rf = additional bond; or 1 or 2 of Ra - Rf may form a 1-3C bridge to R1 or R7; X = 1-6C alkylene; R1 = 1-12C alkyl or 2-12C alkenyl (both optionally substituted (os) by one or more of halo, OH, CN, alkoxy, aralkoxy, alkyl and/or NR12R13); 3-10C cycloalkyl or 3-10C cycloalkenyl (both os by one or more of halo, OH, CN, alkoxy, alkyl and/or NR12R13); or aryl or heteroaryl (both os by one or more of halo, OH, CN, cyanoalkyl, alkoxy, aralkoxy, alkyl, haloalkyl, =O, OR14 and/or R14); R2 = heteroaryl (os by one or more of CN, halo, alkyl, haloalkyl, alkoxy, NH2, OH, OR18 and/or R19), provided that R2 contains at least one N-oxide group; A = -N(R7)-; D = N or CR3; E = N or CR4; J = N or CR5; G = N or CR6; R3 - R6 = H or halo; or alkoxy, alkyl or carboxyalkyl (all os by halo); R7 - R13 = H or alkyl; or R7 forms a 1-3 membered bridge with Ra - Rf or to R1; NR12R13 = heterocycle (optionally containing an additional heteroatom); R14, R18 = (CH2CH2O)u(CH2)v-R15; R15, R19 = aryl, heteroaryl, alkyl, aralkyl, CH2CN or NR16R17; R16, R17 = H, alkyl or 1-6C acyl; NR16R17 = heterocycle (optionally containing an additional heteroatom); u, v = 0-5; Alkyl moieties have 1-6C unless specified otherwise (except that no C-numbers are given for aralkoxy or aralkyl).