890532-46-4

Upstream product

• 807640-16-0 glycine, N-[ (4-chloro-2-nitrophenyl) acetyl]-, ethyl ester 
• 807640-25-1 glycine, N-[[2-[[6-(2-bromoethoxy)-7-methoxy-4-quinazolinyl]amino]-4-chlorophenyl]acetyl]-, ethyl ester 
• 37777-71-2 4-chloro-2-nitro-phenylacetic acid 
• 230955-75-6 6-acetoxy-4-chloro-7-methoxyquinazoline 
• 179688-53-0 7-methoxy-4-oxo-3,4-dihydroquinazolin-6-yl acetate 

Relevant academic research and scientific papers

MTKI QUINAZOLINE DERIVATIVES

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 NH; Y represents -C3-9alkyl-,-C1-5alkyl-NR13-C1-5alkyl-, -C1-5alkyl-NR14-CO-C1-5alkyl-, -C1-2alkyl-NR21-H2-CO-NH-C1-3alkyl- or -C1-2alkyl-NR23-CO-CR16R17-NH-; X1 represents O or -O-C1-2alkyl-; X2 represents a direct bond, C1-2alkyl, -CO-C1-2alkyl or NR12-C1-2alkyl; R1 represents hydrogen or halo; R2 represents halo, acetylene or Het1; R3 represents hydrogen or cyano; R4 represents Ar4-C1-4alkyloxy-, C1-4alkyloxy- or C1-4alkyloxy substituted with one or where possible two or more substituents selected from Het2, NR7R8, hydroxy and C1-4alkyloxy-C1-4alkyloxy-; R7 represents hydrogen or C1-4alkyl; R8 represents C1-4alkyl substituted with NR25R26 or C1-4alkylsulfonyl ; R12 represents hydrogen or C1-4alkyl-; R13 represents Ar6-sulfonyl or C1-6alkyloxycarbonyl optionally substituted with phenyl; R16 and R17 represents hydrogen, C1-4alkyl or R16 and R17 taken together with the carbon atom to which they are attached from a C3-6cycloalkyl; R23 represents C1-4alkyl and R23 represents hydrogen when R16 and R17 taken together with the carbon atom to which they are attached from a C3-6cycloalkyl; R25, R26, R27 and R28 each independently represent hydrogen or C1-4alkylcarbonyl; Het1 represents 2-bora-l,3-dioxolanyl; Het2 represents piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl or 1,1-dioxothiomorpholinyl wherein said Het2 is optionally substituted with C1-4alkyloxycarbonyl or NR27R28-C1-4alkyl; Ar4 and Ar5 represents phenyl; Ar6 represents phenyl optionally substituted with nitro.

MACROCYCLIC QUINAZOLINE DERIVATIVES AS ANTIPROLIFERATIVE AGENTS

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 assays on the receptor tyrosine kinase EGFR.