Tyrphostins .5. Potent inhibitors of platelet-derived growth factor receptor tyrosine kinase: Structure-activity relationships in quinoxalines, quinolines, and indole tyrphostins

被引：248
作者：
Gazit, A
App, H
McMahon, G
Chen, J
Levitzki, A
Bohmer, FD
机构：
[1] HEBREW UNIV JERUSALEM,ALEXANDER SILBERMAN INST LIFE SCI,DEPT BIOL CHEM,JERUSALEM,ISRAEL
[2] SUGEN INC,REDWOOD CITY,CA 94063
[3] UNIV JENA,GROWTH FACTOR SIGNAL TRANSDUCT MED FAC,MAX PLANCK SOC,RES GRP,D-07747 JENA,GERMANY
来源：
JOURNAL OF MEDICINAL CHEMISTRY | 1996年 / 39卷 / 11期
关键词：
D O I：
10.1021/jm950727b
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A series of 3-indoleacrylonitrile tyrphostins, 2-chloro-3-phenylquinolines, and 3-arylquinoxalines were prepared and tested for inhibition of platelet-derived growth factor receptor tyrosine kinase (PDGF-RTK) activity. The potency of the inhibitors was found to be quinoxalines > quinolines > indoles. Lipophilic groups (methyl, methoxy) in the 6 and 7 positions and phenyl at the 3 position of quinoxalines and quinolines were essential for potency, in contrast to the hydrophilic catechol group in tyrphostins active against EGFR kinase inhibition at different sites. The inhibitors showed selectivity for PDGF and were not active against EGF receptor and HER-2/c-ErbB-2 receptor.
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收藏
页码：2170 / 2177
页数：8
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