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

Abstract：

: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.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Gazit A,App H,McMahon G,Chen J,Levitzki A,Bohmer FD

doi

10.1021/jm950727b

subject

Has Abstract

pub_date

1996-05-24 00:00:00

pages

2170-7

issue

11

eissn

0022-2623

issn

1520-4804

pii

jm950727b

journal_volume

39

pub_type

杂志文章

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