کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1377231 | 981974 | 2006 | 5 صفحه PDF | دانلود رایگان |
A new class of tumor necrosis factor alpha (TNF-α) 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-α 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 p38α 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.
A new class of tumor necrosis factor alpha (TNF-α) synthesis inhibitors based on an N-2,4-pyrimidine-N-phenyl-N′-alkyl urea scaffold is described.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 16, Issue 13, 1 July 2006, Pages 3514–3518