Quinazoline compounds

Abstract

The invention relates to compounds of the formula (I): wherein ring C is as defined herein, for example indolyl, indazolyl or azaindolyl; Z is —O—, —NH— or —S—; n is 0-5; m is 0-3; R 1 and R 2 are defined herein including groups: (i) Q 1 X 1 wherein Q 1 and X 1 are as defined herein; (ii) Q 15 W 3 wherein Q 15 and W 3 are as defined herein, (iii) Q 21 W 4 C 1-5 alkylX 1 — wherein Q 21 , W 4 and X 1 are as defined herein, (iv) Q 28 C 1-5 alkylX 1 —, Q 28 C 2-5 alkenylX 1 — or Q 28 C 2-5 alkynylX 1 — wherein Q 28 and X 1 are as defined herein and (v) Q 29 C 1-5 alkylX 1 —, Q 29 C 2-5 alkenylX 1 — or Q 29 C 2-5 alkynylX 1 — wherein Q 29 and X 1 are as defined herein; R 2 can also be 6,7-methylenedioxy or 6,7-ethylenedioxy; and salts thereof; their use 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; intermediates used in such processes; processes for making such intermediates; pharmaceutical compositions containing a compound of formula I or a pharmaceutically acceptable salt thereof and methods of treating disease states involving angiogenesis by administering a compound of formula I or a pharmaceutically acceptable salt thereof. The compounds of formula I inhibit the effects of VEGF, a property of value in the treatment of a number of disease states including cancer and rheumatoid arthritis.

1 - 25 . (canceled) 
   
   
       26 . A process for the production of 5-methoxy-7-azaindole comprising mixing a solution of the following materials in relative quantities according to the amounts given herein:
 5-bromo-7-azaindole (8.6 g, 44 mmol), copper (I) bromide (12.6 g, 88 mmol) and sodium methoxide (100 g, 1.85 mol) in a mixture of “degassed” DMF (260 mls) and methanol (175 mls);   stirring the resulting mixture at ambient temperature in a nitrogen atmosphere; and then heating the mixture at reflux.