2,4, (4,6) PYRIMIDINE DERIVATIVES

• Main Authors: ROMBOUTS, FREDERIK JAN RITA, FREYNE, EDDY JEAN EDGARD, WILLEMS, MARC, VAN BRANDT, SVEN FRANCISCUS ANNA, EMBRECHTS, WERNER CONSTANT JOHAN, VAN EMELEN, KRISTOF
• Format: Patent
• Language: English
• Published: 11.04.2019

The present invention concerns the compounds of formula (I), the N-oxide fonns, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein Z1 and Z2 represent NH; Y represents -C3_9alkyl-, -C3_9alkenyl-, -C1 -salkyl-NR 6- C1 -salkyl-, -C1_5alkyl-NR 7- CO-C1 _ 5alkyl-, -C1-6alkyl-CO-NH-, -C1-6alkyl-NH-CO-, -C1 _2a lkyl-CO-H et10-CO-, -C1 _ 3alkyl-NH-CO-H et3-, -Het4-C1_3alkyl-CO-NH-C 1 _3alkyl-, -C1-2alkyl-NH-CO-L1- NH-, -NH-CO-L2-NH-, -C1-2 alkyl-CO-NH-L 3-CO-, -C1_2alkyl-NH-CO-L 1 -NH-CO- C1_3alkyl-, -C1 -2alkyl-CO-NH-L 3-CO-NH-C 1_3alkyl-, -C 1-2alkyl-NR 11 -CH2- CO-NH-C1_3alkyl-, Het5-CO-C1 -2alkyl-, -C1 _5alkyl-CO-NH-C 1 _3alkyl-CO-NH-, -C1 _5alkyl-NR 1 3-CO-C1 _3alkyl-NH-, -C1 _3alkyl-NH-CO-Het27- CO-, or -C1 _3alkyl-CO- Het28-CO-NH-?, X1 represents a direct bond, 0, -O-C1 _2alkyl-, -CO-C1 _2alkyl-, -NR16-C1 _2alkyl-, -CO- NR17-, Het23- C1 _2alkyl- or C1-2alkyl; X2 represents a direct bond, 0, -O-C1 _2alkyl-, -CO-C1 _2alkyl-, -NR18 -C1 _2alkyl-, -CO- NR19-, Het24-C1-2alkyl- or C1-2alkyl; R1 and R5 each independently represent hydrogen, halo, C1_6alkyloxy- or C1 _6alkyloxy- substituted with Het1 or C1-4alkyloxy-; R2 and R4 each independently represent hydrogen or halo; R3 represents hydrogen or cyano; R6, R7, R1 3, R17 and R19 represent hydrogen; R11 represents hydrogen or C14 alkyl; R16 and R18 represent hydrogen, C14 a lkyl or Het17 -C14 alkyl-; L1 , L2 and L3 each independently represents C1 _8al kyl optionally substituted with one or where possible two or more substituents selected from phenyl, methylsulfide, cyano, polyhaloC1-4alkyl-phenyl-, C1-4alkyloxy, pyridinyl, mono- or di(C14 a lkyl)- amino- or C3_6cycloalkyl; Het1 , Het 2, Het 17 each independently represent morpholinyl, oxazolyl, isoxazolyl, or piperazinyl; Het3, Het 4, Het5 each independently represent morpholinyl, piperazinyl, piperidinyl or pyrrolidinyl; Het 1 0 represents piperazinyl, piperidinyl, pyrrolidinyl or azetidinyl; Het22 represents morpholinyl, oxazolyl, isoxazolyl or piperazinyl wherein said Het22 is optionally substituted with C14 a lkyl; Het23 and He t24 each independently represent a heterocycle selected from pyrrolidinyl, piperazinyl or piperidinyl wherein said Het23 or Het24 are optionally substituted with Het 22-carbonyl; Het 27 and Het28 each independently represent a heterocycle selected from morpholinyl, piperazinyl, piperidinyl or pyrrolidinyl.