申请人:Thomas Peter Andrew
公开号:US20050239777A1
公开(公告)日:2005-10-27
The invention relates to quinazoline derivatives of formula (1)
wherein m is an integer from 1 to 2; R
1
represents hydrogen, hydroxy, halogeno, nitro, trifluoromethyl, cyano, C
1-3
alkyl, C
1-3
alkoxy, C
1-3
alkylthio, or —NR
5
R
6
(wherein R
5
and R
6
, which may be the same or different, each represents hydrogen or C
1-3
alkyl); R
2
represents hydrogen, hydroxy, halogeno, methoxy, amino or nitro; R
3
represents hydroxy, halogeno, C
1-3
alkyl, C
1-3
alkoxy, C
1-3
alkanoyloxy, trifluoromethyl, cyano, amino or nitro; X
1
represents —O—, —CH
2
—, —S—, —SO—, —SO
2
—, —NR
7
CO—, —CONR
8
—, —SO
2
NR
9
—, —NR
10
SO
2
— or —NR
11
— (wherein R
7
, R
8
, R
9
, R
10
and R
11
each independently represents hydrogen, C
1-3
alkyl or C
1-3
alkoxyC
2-3
alkyl); R
4
represents an optionally substituted 5 or 6 membered saturated carbocyclic or heterocyclic group or a group which is alkenyl, alkynyl or optionally substituted alkyl, which alkyl group may contain a heteroatom linking group, which alkenyl, alkynyl or alkyl group may carry a terminal optionally substituted group selected from alkyl and a 5 or 6 membered saturated carbocyclic or heterocyclic group, and salts thereof; processes for their preparation, pharmaceutical compositions containing a compound of formula (I) or a pharmaceutically acceptable salt thereof as active ingredient. The compounds of formula (I) and 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.
本发明涉及公式(1)的喹唑啉衍生物,其中m为1到2的整数;R1代表氢、羟基、卤素、硝基、三氟甲基、氰基、C1-3烷基、C1-3烷氧基、C1-3烷硫基或-NR5R6(其中R5和R6可以相同或不同,每个代表氢或C1-3烷基);R2代表氢、羟基、卤素、甲氧基、氨基或硝基;R3代表羟基、卤素、C1-3烷基、C1-3烷氧基、C1-3酰氧基、三氟甲基、氰基、氨基或硝基;X1代表-O-、-CH2-、-S-、-SO-、-SO2-、-NR7CO-、-CONR8-、-SO2NR9-、-NR10SO2-或-NR11-(其中R7、R8、R9、R10和R11各自独立地代表氢、C1-3烷基或C1-3烷氧基C2-3烷基);R4代表可选取代的5或6成员饱和碳环或杂环基或烯基、炔基或可选取代的烷基,其中烷基基团可以包含一个杂原子连接基团,烯基、炔基或烷基基团可以携带一个末端可选取代的基团,所选的基团为烷基或5或6成员饱和碳环或杂环基,以及其盐;制备它们的方法,含有公式(I)化合物或其药学上可接受的盐作为活性成分的制药组合物。公式(I)化合物及其药学上可接受的盐抑制VEGF的作用,在治疗包括癌症和类风湿性关节炎在内的多种疾病状态中具有价值的特性。