2. Academic Validation
  3. The development of monocyclic pyrazolone based cytokine synthesis inhibitors

The development of monocyclic pyrazolone based cytokine synthesis inhibitors

  • Bioorg Med Chem Lett. 2005 May 2;15(9):2285-9. doi: 10.1016/j.bmcl.2005.03.007.
Adam Golebiowski 1,  Jennifer A Townes,  Matthew J Laufersweiler,  Todd A Brugel,  Michael P Clark,  Cynthia M Clark,  Jane F Djung,  Steven K Laughlin,  Mark P Sabat,  Roger G Bookland,  John C VanRens,  Biswanath De,  Lily C Hsieh,  Michael J Janusz,  Richard L Walter,  Mark E Webster,  Marlene J Mekel
Affiliations

Affiliation

  • 1 Procter and Gamble Pharmaceuticals, Health Care Research Center, 8700 Mason-Montgomery Rd, Mason, OH 45040, USA. [email protected]
PMID: 15837310 DOI: 10.1016/j.bmcl.2005.03.007
Abstract

4-Aryl-5-pyrimidyl based cytokine synthesis inhibitors that contain a novel monocyclic, pyrazolone heterocyclic core are described. Many of these inhibitors showed low nanomolar activity against LPS-induced TNF-alpha production. One of the compounds (6e) was found to be efficacious in the rat iodoacetate (RIA) in vivo model of osteoarthritis. The X-ray crystal structure of a pyrazolone inhibitor cocrystallized with mutated p38 (mp38) is presented.

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