2. Academic Validation
  3. Development of orally bioavailable bicyclic pyrazolones as inhibitors of tumor necrosis factor-alpha production

Development of orally bioavailable bicyclic pyrazolones as inhibitors of tumor necrosis factor-alpha production

  • J Med Chem. 2004 May 20;47(11):2724-7. doi: 10.1021/jm049968m.
Michael P Clark 1,  Steven K Laughlin,  Matthew J Laufersweiler,  Roger G Bookland,  Todd A Brugel,  Adam Golebiowski,  Mark P Sabat,  Jennifer A Townes,  John C VanRens,  Jane F Djung,  Michael G Natchus,  Biswanath De,  Lily C Hsieh,  Susan C Xu,  Rick L Walter,  Marlene J Mekel,  Sandra A Heitmeyer,  Kimberly K Brown,  Karen Juergens,  Yetunde O Taiwo,  Michael J Janusz
Affiliations

Affiliation

  • 1 Health Care Research Center, Procter and Gamble Pharmaceuticals, 8700 Mason-Montgomery Road, Mason, Ohio 45040, USA. [email protected]
PMID: 15139749 DOI: 10.1021/jm049968m
Abstract

2-Aryl-3-pyrimidinyl based tumor necrosis factor-alpha (TNF-alpha) inhibitors, which contain a novel bicyclic pyrazolone core, are described. Many showed low-nanomolar activity against lipopolysaccharide-induced TNF-alpha production in monocytic cells. Secondary screening data are presented for the pyrimidinyl bicyclic pyrazolones. Several of these analogues showed good oral bioavailability in rat and efficacy in the rat iodoacetate in vivo model.

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