2,4 (4,6) PYRIMIDINE DERIVATIVES.

摘要

The present invention concerns the compounds of formula (I), the N-oxideforms, the pharmaceutically acceptable addition salts and the stereochemicallyisomeric forms thereof, wherein Z1 and Z2 represent NH;Y represents -C3-9alkyl-, -C3-9alkenyl-, -C1-5alkyl-NR6-C1-5alkyl-,-C1-5alkyl-NR7-CO-C1 -5alkyl-, -C1-6alkyl-CO-NH-,-C1-6alkyl-NH-CO-, -C1-2alkyl-CO-Het10-CO-,-C1-3alkyl-NH-CO-Het3-, -Het4-C1-3alkyl-CO-NH-C1-3alkyl-,-C1-2alkyl-NH-CO-L1-NH-, -NH-CO-L2-NH-,-C1-2alkyl-CO-NH-L3-CO-, -C1-2alkyl-NH-CO-L1-NH-CO-C1-3alkyl-,-C1-2alkyl-CO-NH-L3-CO-NH- C1-3alkyl-, -C1-2alkyl-NR11-CH2-CO-NH-C1-3alkyl-,Het5-CO-C1-2alkyl-, -C1-5alkyl-CO-NH-C1-3alkyl-CO-NH-,-C1-5alkyl-NR13-CO-C1-3alkyl- NH-, -C1-3alkyl-NH-CO-Het27-CO-,or -C1-3alkyl-CO-Het28-CO-NH-; X1 representsa direct bond, O, -O-C1-2alkyl-, -CO-C1-2alkyl-, -NR16-C1-2alkyl-,-CO-NR17-, Het23-C1-2alkyl- or C1-2alkyl;X2 represents a direct bond, O, -O-C1-2alkyl-, -CO-C1-2alkyl-,-NR18-C1-2alkyl-, -CO-NR19-, Het24-C1-2alkyl-or C1-2alkyl; R1 and R5 each independently representhydrogen, halo, C1-6alkyloxy- or C1-6alkyloxy- substitutedwith Het1 or C1-4alkyloxy-; R2 and R4each independently represent hydrogen or halo; R3 represents hydrogenor cyano; R6, R7, R13, R17 and R19represent hydrogen; R11 represents hydrogen or C1-4alkyl;R16and R18 represent hydrogen, C1-4alkyl orHet17-C1-4alkyl-; L1, L2 and L3each independently represents C1-8alkyl optionally substitutedwith one or where possible two or more substituents selected from phenyl, methylsulfide,cyano, polyhaloC1-4alkyl-phenyl-, C1-4alkyloxy, pyridinyl,mono- or di(C1-4alkyl)-amino- or C3-6cycloalkyl; Het1, Het2, Het17 each independently represent morpholinyl,oxazolyl, isoxazolyl, or piperazinyl; Het3, Het4, Het5each independently represent morpholinyl, piperazinyl, piperidinyl or pyrrolidinyl;Het10 represents piperazinyl, piperidinyl, pyrrolidinyl or azetidinyl;Het22 represents morpholinyl, oxazolyl, isoxazolyl or piperazinylwherein said Het22 is optionally substituted with C1-4alkyl ;Het23 and Het24 each independently represent a heterocycleselected from pyrrolidinyl, piperazinyl or piperidinyl wherein said Het23or Het24 are optionally substituted with Het22-carbonyl;Het27 and Het28 each independently represent a heterocycleselected from morpholinyl, piperazinyl, piperidinyl or pyrrolidinyl.