Astrazeneca Ab

Astra Zeneca U.k. Limited

Laurent F A Hennequin

Patrick Ple

Darren Mckerrecher

Elaine S E Stokes

Graham C Crawley

Jeffrey Philip Poyser

Georges Rene Pasquet

Christine M P Lambert

The invention relates to the use of compounds of formula (I) 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. 

Quinazoline derivatives as angiogenesis inhibitors

The invention relates to the use of compounds of the formula I: wherein: ring C is a 5-6 membered heterocyclic moiety; Z is &#x2014;O&#x2014;, &#x2014;S&#x2014;, or &#x2014;CH&#x2014;; Ris hydrogen, Calkyl, Calkoxymethyl, di(C)alkoxy)methyl, Calkanoyl, trifluoromethyl, cyano, amino, Calkenyl, Calkynyl, carboxy, Ccycloalkyl, C-cycloalkylCalkyl, or an optionally substituted group selected from phenyl, benzyl, phenylCalkyl and a 5-6 membered heterocyclic group; n is an integer from 0 to 5; m is an integer from 0 to 3; Rrepresents hydrogen, hydroxy, halgeno, cyano, nitro, trifluoromethyl, Calkyl, Calkoxy, Calkylsulphanyl, &#x2014;NRR(wherein Rand R, which may be the same or different, each represents hydrogen or Calkyl), or RX&#x2014; (wherein Xrepresents a direct bond, &#x2014;CH&#x2014;, or a heteroatom linker group and Ris 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 Ris 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 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.

Quinazoline derivatives

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&#x2013;3 heteroatoms selected independently from O, N and S; Z is &#x2014;O&#x2014;, &#x2014;NH&#x2014;, &#x2014;S&#x2014;, &#x2014;CH&#x2014; or a direct bond; n is 0&#x2013;5; m is 0&#x2013;3; Rrepresents hydrogen, hydroxy, halogeno, cyano, nitro, trifluoromethyl, Calkyl, Calkoxy, Calkylsulphanyl, &#x2014;NRR(wherein Rand R, which may be the same or different, each represents hydrogen or Calkyl), or RX&#x2014; (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&#x2014;Calkylcarbamoyl, N,N-di(Calkylcarbamoyl, aminosulphonyl, N&#x2014;Calkylaminosulphonyl, N,N-di(Calkyl)aminosulphonyl, N&#x2014;(Calkylsulphonyl)amino, N&#x2014;(Calkylsulphonyl)-N&#x2014;(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. 

The invention concerns quinazoline derivatives of Formula (I) wherein Q includes a quinazoline ring optionally substituted with a group such as halogeno, trifluoromethyl and cyano, or a group of the formula: Q &mdash;X &mdash; wherein X includes a direct bond and O and Q includes aryl, aryl-(1-6C)alkyl, heterocyclyl and heterocyclyl-(1-6C)alkyl; each of R and R is hydrogen or (1-6C)alkyl; Z includes O, S and NH; and Q includes aryl and aryl-(1-3C)alkyl or a pharmaceutically-acceptable salt thereof; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use in the prevention or treatment of T cell mediated diseases or medical conditions in a warm-blooded animal.

Growing community of inventors

Reims, France

Laurent F A Hennequin