QUINAZOLINE DERIVATIVES

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-; R<1> is hydrogen, C1-4alkyl, 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, C1-3alkyl, C1-3alkoxy, C1-3alkylsulphanyl, -NR<3>R<4> (wherein R<3> and R<4>, which may be the same or different, each represents hydrogen or C1-3alkyl), or R<5>X<1>- (wherein X<1> represents a direct bond, -CH2-, 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 R<5> 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.