申请人：——
公开号：US20030212055A1
公开（公告）日：2003-11-13
The invention relatest to compounds of the formula (I) wherein either any one of G
1
, G
2
, G
3
, G
4
and G
5
is nitrogen and the other four are —CH—, or G
1
, G
2
, G
3
, G
4
and G
5
are all —CH—; Z is —O—, —NH—, —S—, —CH
2
— or a direct bond; Z is linked to any one of G
1
, G
2
, G
3
and G
4
which is a free carbon atom; n is an integer from 0 to 5; any of the substitutents R
1
may be attached at any free carbon atom of the indole, azaindole or indazole group; m is an integer from 0 to 3; R
a
represents hydrogen; R
b
represents hydrogen or another value as defined herein; R
1
represents hydrogen, oxo, hydroxy, halogeno, C
1-4
alkyl, C
1-4
alkoxy, C
1-4
alkoxy, C
1-4
-alkyl, aminoC
1-4
alkyl, C
1-3
alkylaminoC
1-4
alkyl, di(C
1-3
alkyl)aminoC
1-4
alkyl, —C
1-5
alkyl(ring B) wherein ring B is selected from azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, N-methylpiperazinly, N-ethylpiperazinyl, morpholino and thiomorpholino; R
2
represents hydrogen, hydroxy, halogeno, cyano, nitro, trifluoromethyl, C
1-3
alkyl, C
1-3
alkoxy, C
1-3
aklylsulphanyl, —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 R
5
and X
1
are as defined herein) and salts thereof, 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 the use of a compound of formula I in the manufacture of medicament for the production of an antiangiogenic and/or vascular permeability reducing effect in warm-blooded animals. 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.
该发明涉及以下式(I)的化合物，其中G1、G2、G3、G4和G5中的任何一个是氮，其他四个是—CH—，或者G1、G2、G3、G4和G5都是—CH—；Z是—O—、—NH—、—S—、—CH2—或直接键；Z与G1、G2、G3和G4中的任何一个自由碳原子相连；n是从0到5的整数；R1的任何取代基可能连接到吲哚、氮杂吲哚或吲唑基团的任何自由碳原子；m是从0到3的整数；Ra代表氢；Rb代表氢或本文中定义的另一个值；R1代表氢、氧代、羟基、卤代、C1-4烷基、C1-4烷氧基、C1-4烷氧基、C1-4烷基、氨基C1-4烷基、C1-3烷基氨基C1-4烷基、二(C1-3烷基)氨基C1-4烷基、—C1-5烷基(环B)，其中环B选自氮杂环丙烷基、吡咯烷基、哌啶基、哌嗪基、N-甲基哌嗪基、N-乙基哌嗪基、吗啉和硫代吗啉；R2代表氢、羟基、卤代、氰基、硝基、三氟甲基、C1-3烷基、C1-3烷氧基、C1-3烷基硫基、—NR3R4(其中R3和R4，可能相同也可能不同，各自代表氢或C1-3烷基)，或R5X1—(其中R5和X1如本文所定义)及其盐，制备这类化合物的方法，含有式I的化合物或其药学上可接受的盐作为活性成分的药物组合物，以及利用式I的化合物制备药物，用于在温血动物中产生抗血管生成和/或血管通透性降低作用。式I的化合物及其药学上可接受的盐抑制VEGF的作用，这是治疗多种疾病状态的有价值特性，包括癌症和类风湿性关节炎。
