当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY LETTERS期刊下所有文献 > Development of N-2,4-pyrimidine-N-phenyl-N'-alkyl ureas as orally active inhibitors of tumor necrosis factor alpha (TNF-alpha) synthesis. Part 2.

Development of N-2,4-pyrimidine-N-phenyl-N'-alkyl ureas as orally active inhibitors of tumor necrosis factor alpha (TNF-alpha) synthesis. Part 2.

Abstract：

:A new class of tumor necrosis factor alpha (TNF-alpha) synthesis inhibitors based on a N-2,4-pyrimidine-N-phenyl-N'-alkyl urea scaffold is described. Many of these compounds showed low-nanomolar activity against lipopolysaccharide stimulated TNF-alpha production. Two analogs were tested in an in vivo rat iodoacetate model of osteoarthritis and shown to be orally efficacious. X-ray co-crystallization studies with mutated p38alpha showed that these trisubstituted ureas interact with the ATP-binding pocket in a pseudo-bicyclic conformation brought about by the presence of an intramolecular hydrogen bonding interaction.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Maier JA,Brugel TA,Clark MP,Sabat M,Golebiowski A,Bookland RG,Laufersweiler MJ,Laughlin SK,Vanrens JC,De B,Hsieh LC,Brown KK,Juergens K,Walter RL,Janusz MJ

doi

10.1016/j.bmcl.2006.03.096

subject

Has Abstract

pub_date

2006-07-01 00:00:00

pages

3514-8

issue

13

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(06)00401-X

journal_volume

16

pub_type

杂志文章

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