Invention Grant
US07648975B2 Macrocyclic quinazoline derivatives as antiproliferative agents 有权
大环喹唑啉衍生物作为抗增殖剂

Macrocyclic quinazoline derivatives as antiproliferative agents
Abstract:
The present invention concerns the compounds of formula (I) the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein Z represents O, CH2, NH or S; in particular Z represents NH; Y represents —C3-9alkyl-, —C3-9alkenyl-, —C3-9alkynyl-, —C3-7alkyl-CO—NH— optionally substituted with amino, mono- or di(C1-4alkyl)amino or C1-4 alkyloxycarbonylamino-, —C3-7alkenyl-CO—NH— optionally substituted with amino, mono- or di(C1-4alkyl)amino- or C1-4alkyloxycarbonylamino-, C1-5alkyl-oxy-C1-5alkyl-, —C1-5alkyl NR13—, —C1-5alkyl-, —C1-5alkyl-NR14—CO—C1-5alkyl-, —C1-5alkyl-CO NR15—C1-5alkyl-, —C1-6alkyl-CO—NH—, —C1-6alkyl-NH—CO—, —C1-3alkyl-NH—CS-Het20-, —C1-3alkyl-NH—CO-Het20, —C1-2alkyl-CO-Het21-CO—, -Het22-CH2—CO—NH—C1-3alkyl-, —CO—NH—C1-6alkyl-, —NH—CO—C1-6alkyl-, —CO—C1-7alkyl-, —C1-7alkyl-CO—, —C1-6alkyl-CO—C1-6alkyl-, —C1-2alkyl-NH—CO—CR16R17—NH—, —C1-2alkyl-CO—NH—CR18R19—CO—, —C1-2alkyl-CO—NR20—C1-3alkyl-CO—, C1-2alkyl-NR21—CH2—CO—NH—C1-3alkyl-, or NR22—CO—C1-3alkyl-NH—, X1 represents a direct bond, O or —O—C1-2alkyl-, CO, —CO—C1-2alkyl-, NR11, —NR11—C1-2alkyl-, —CH2—, —O—N═CH— or —C1-2alkyl-; X2 represents a direct bond, O, —O—C1-2alkyl-, CO, —CO—C1-2alkyl-, NR12, —NR12—C1-2alkyl-, —CH2—, —O—N═CH— or —C1-2alkyl-. The growth inhibitory effect anti-tumour activity of the present compounds has been demonstrated in vitro, in enzymatic on the receptor tyrosine kinase EGFR.
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