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Design and synthesis of 4-azaindoles as inhibitors of p38 MAP kinase.

Abstract：

:Inhibition of the biosynthesis of proinflammatory cytokines such as tumor necrosis factor and interleukin-1 via p38 has been an approach toward the development of a disease modifying agent for the treatment of chronic inflammation and autoimmune diseases. The development of a new core structure of p38 inhibitors, 3-(4-fluorophenyl)-2-(pyridin-4-yl)-1H-pyrrolo[3,2-b] pyridine, is described. X-ray crystallographic data of the lead bound to the active site of p38 was used to guide the optimization of the series. Specific focus was placed on modulating the physical properties of the core while maintaining potent inhibition of p38. These efforts identified 42c as a potent inhibitor of p38, which also possessed the required physical properties worthy of advanced studies.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Trejo A,Arzeno H,Browner M,Chanda S,Cheng S,Comer DD,Dalrymple SA,Dunten P,Lafargue J,Lovejoy B,Freire-Moar J,Lim J,Mcintosh J,Miller J,Papp E,Reuter D,Roberts R,Sanpablo F,Saunders J,Song K,Villasenor A,Warren

doi

10.1021/jm0301787

keywords:

subject

Has Abstract

pub_date

2003-10-23 00:00:00

pages

4702-13

issue

22

eissn

0022-2623

issn

1520-4804

journal_volume

46

pub_type

杂志文章

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