2. Academic Validation
  3. The development of new bicyclic pyrazole-based cytokine synthesis inhibitors

The development of new bicyclic pyrazole-based cytokine synthesis inhibitors

  • Bioorg Med Chem Lett. 2004 Oct 4;14(19):4945-8. doi: 10.1016/j.bmcl.2004.07.024.
Jennifer A Townes 1,  Adam Golebiowski,  Michael P Clark,  Matthew J Laufersweiler,  Todd A Brugel,  Mark Sabat,  Roger G Bookland,  Steve K Laughlin,  John C VanRens,  Biswanath De,  Lily C Hsieh,  Susan C Xu,  Michael J Janusz,  Richard L Walter
Affiliations

Affiliation

  • 1 Procter and Gamble Pharmaceuticals, Health Care Research Center, 8700 Mason-Montgomery Rd, Mason, OH 45040, USA. [email protected]
PMID: 15341957 DOI: 10.1016/j.bmcl.2004.07.024
Abstract

4-Aryl-5-pyrimidyl-based cytokine synthesis inhibitors of TNF-alpha production, which contain a novel bicyclic pyrazole heterocyclic core, are described. Many of these inhibitors showed low nanomolar activity against LPS-induced TNF-alpha production in a THP-1 cell-based assay and against human p38 alpha MAP kinase in an isolated enzyme assay. The X-ray crystal structure of a bicyclic pyrazole inhibitor co-crystallized with mutated p38 (mp38) is presented.

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