QUINAZOLINE COMPOUNDS

摘要

The invention concerns compounds of the formula (I) wherein ring A is phenyl or 5- or 6-membered heterocyclic ring as defined herein; Z is -O-, -NH- or -S-; m is an integer from 0 to 5 inclusive; R1 is hydrogen, hydroxy, halogeno, nitro, trifluoromethyl, cyano, C¿1-3?alkyl, C1-3alkoxy, C1-3alkylthio, or -NR?5R6¿ (wherein R?5 and R6¿, which may be the same or different, are hydrogen or C¿1-3?alkyl); R?2¿ is hydrogen, hydroxy, halogeno, C¿1-3?alkyl, C1-3alkoxy, trifluoromethyl, amino or nitro; R?3¿ is hydroxy, halogeno, C¿1-3?alkyl, C1-3alkoxy, C1-3alkanoyloxy, trifluoromethyl, cyano, amino or nitro; provided that when ring A is a 5- or 6-membered heterocyclic ring, at least one R?3¿ is either hydroxy or halogeno; X1 is -O-, -CH¿2?-, -S-, -SO-, -SO2-, -NR?7-, -NR7¿CO-, -CONR7-, -SO¿2NR?7- or -NR7SO2-, (wherein R7 is hydrogen, C¿1-3?alkyl or C1-3alkoxyC2-3alkyl); and R?4¿ is selected from a number of groups defined herein comprising an C¿2-5?alkylene, C3-5alkenylene or C3-5alkynylene chain wherein each methylene group (other than that of the α-carbon) is optionally substituted by 1 substituent independently selected from hydroxy, halogeno, amino and C1-4alkanoyloxy; provisos are as defined herein. The invention also relates to pharmaceutical compositions comprising a compound of formula (I), to the use of a compound of formula (I) in the manufacture of a medicament for use in the production of an antiangiogenic and/or vascular permeability reducing effect in a warm-blooded animal and to a method for producing an antiangiogenic and/or vascular permeability reducing effect in a warm-blooded animal in need of such treatment. The compounds are useful in disease states such as cancer, rheumatoid arthritis and psoriasis.