QUINAZOLINE DERIVATIVES AS INHIBITORS OF VEGF RECEPTOR TYROSINE KINASES

摘要

The present invention relates to compounds of the Formula (I): wherein Z is -NH-, -O- or -S-; R <1 >represents bromo or chloro; R <3 >represents C 1-3 alkoxy or hydrogen; R <2 >is selected from one of the following three groups: (i) Q <1 >X <1 >- wherein X <1 >and Q <1 >are as defined herein; (ii) Q <15 >W <3 >- wherein Q <15 >and W <3 >are as defined herein; and (iii) Q <21 >W <4 >C 1-5 alkylX <1 >wherein X <1 >, W <4 >and Q <21 >are as defined herein; 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; 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.