Quinazoline derivatives as angiogenesis inhibitors

Abstract

The invention relates to the use of compounds of formula (I), wherein ring C is an 8, 9, 10, 12 or 13-membered bicyclic or tricyclic moiety which optionally may contain 1–3 heteroatoms selected independently from O, N and S; Z is —O—, —NH—, —S—, —CH— or a direct bond; n is 0–5; m is 0–3; Rrepresents hydrogen, hydroxy, halogeno, cyano, nitro, trifluoromethyl, Calkyl, Calkoxy, Calkylsulphanyl, —NRR(wherein Rand R, which may be the same or different, each represents hydrogen or Calkyl), or RX— (wherein Xand Rare as defined herein; Rrepresents hydrogen, oxo, halogeno, hydroxy, Calkoxy, Calkyl, Calkoxymethyl, Calkanoyl, Chaloalkyl, cyano, amino, Calkenyl, Calkynyl, Calkanoyloxy, nitro, Calkanoylamino, Calkoxycarbonyl, Calkylsulphanyl, Calkylsulphinyl, Calkylsulphonyl, carbamoyl, N—Calkylcarbamoyl, N,N-di(Calkylcarbamoyl, aminosulphonyl, N—Calkylaminosulphonyl, N,N-di(Calkyl)aminosulphonyl, N—(Calkylsulphonyl)amino, N—(Calkylsulphonyl)-N—(Calkyl)amino, N,N-di(Calkylsulphonyl)amino, a Calkylene chain joined to two ring C carbon atoms, CalkanoylaminoCalkyl, carboxy or a group RX(wherein Xand Rare as defined herein); 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 ingredient 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.