Intermediates for the preparation of angiogenesis inhibitory quinazoline derivatives

The invention relates to the use of compounds of the 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 2 - or a direct bond; n is 0-5; m is 0-3; R 2 re...

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Bibliographische Detailangaben
Hauptverfasser: MCKERRECHER DARREN, PLE PATRICK, STOKES ELAINE SOPHIE ELIZABETH, HENNEQUIN LAURENT FRANCOIS ANDRE
Format: Patent
Sprache:eng ; hun
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Zusammenfassung:The invention relates to the use of compounds of the 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 2 - or a direct bond; n is 0-5; m is 0-3; R 2 represents hydrogen, hydroxy, halogeno, cyano, nitro, trifluoromethyl, C 1-3 alkyl, C 1-3 alkoxy, C 1-3 alkylsulphanyl, -NR 3 R 4 (wherein R 3 and R 4 , which may be the same or different, each represents hydrogen or C 1-3 alkyl), or R 5 X 1 - (wherein X 1 and R 5 are as defined herein; R 1 represents hydrogen, oxo, halogeno, hydroxy, C 1-4 alkoxy, C 1-4 alkyl, C 1-4 alkoxymethyl, C 1-4 alkanoyl, C 1-4 haloalkyl, cyano, amino, C 2-5 alkenyl, C 2-5 alkynyl, C 1-3 alkanoyloxy, nitro, C 1-4 alkanoylamino, C 1-4 alkoxycarbonyl, C 1-4 alkylsulphanyl, C 1-4 alkylsulphinyl, C 1-4 alkylsulphonyl, carbamoyl, N- C 1-4 alkylcarbamoyl, N , N -di(C 1-4 alkyl)carbamoyl, aminosulphonyl, N -C 1-4 alkylaminosulphonyl, N , N -di(C 1-4 alkyl)ammosulphonyl, N -(C 1-4 alkylsulphonyl)amino, N- (C 1-4 alkylsulphonyl)- N -(C 1-4 alkyl)amino, N , N -di(C 1-4 alkylsulphonyl)amino, a C 3-7 alkylene chain joined to two ring C carbon atoms, C 1-4 alkanoylaminoC 1-4 alkyl, carboxy or a group R 56 X 10 (wherein X 10 and R 56 are 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.