QUINAZOLINE DERIVATIVES, PROCESSES FOR THEIR PREPARATION, PHARMACEUTICAL COMPOSITIONS CONTAINING THEM AND THEIR USE IN THE MANUFACTURE OF MEDICAMENTS HAVING AN ANTIANGIOGENIC AND/OR VASCULAR PERMEABILITY REDUCING EFFECT

摘要

The invention relates to the use of compounds of formula (I), wherein: ring C is a 5-6-membered heterocyclic moiety; Z is -O-, -NH-, -S- or -CH2-; R1 is hydrogen, C¿1-4?alkyl, C1-4alkoxymethyl, di(C1-4alkoxy)methyl, C1-4alkanoyl, trifluoromethyl, cyano, amino, C2-5alkenyl, C2-5alkynyl, carboxy, C3-7cycloalkyl,C3-7cycloalkyl C1-3alkyl, or an optionally substituted group selected from phenyl, benzyl, phenylC2-4alkyl and a 5-6-membered heterocyclic group; n is an integer from 0 to 5; m is an integer from 0 to 3; R?2¿ represents hydrogen, hydroxy, halogeno, cyano, nitro, trifluoromethyl, C¿1-3?alkyl, C1-3alkoxy, C1-3alkylsulphanyl, -NR?3R4¿ (wherein R?3 and R4¿, which may be the same or different, each represents hydrogen or C¿1-3?alkyl), or R?5X1¿- (wherein X1 represents a direct bond, -CH¿2?-, or a heteroatom linker group and R?5¿ is an alkyl, alkenyl or alkynyl chain optionally substituted by for example hydroxy, amino, nitro, alkyl, cycloalkyl, alkoxyalkyl, or an optionally substituted group selected from pyridone, phenyl and a heterocyclic ring, which alkyl, alkenyl or alkynyl chain may have a heteroatom linker group, or R5 is an optionally substituted group selected from pyridone, phenyl and a heterocyclic ring, and salts thereof, in the manufacture of a medicament for use in the production of an antiangiogenic and/or vascular permeability reducing effect in warm-blooded animals, processes for the preparation of such compounds, pharmaceutical compositions containing a compound of formula (I) or a pharmaceutically acceptable salt thereof as active ingredients and compounds of formula (I). The compounds of formula (I) and the pharmaceutically acceptable salts thereof inhibit the effects of VEGF, a property of value in the treatment of a number of disease states including cancer and rheumatoid arthritis.