2. Academic Validation
  3. The development of novel C-2, C-8, and N-9 trisubstituted purines as inhibitors of TNF-alpha production

The development of novel C-2, C-8, and N-9 trisubstituted purines as inhibitors of TNF-alpha production

  • Bioorg Med Chem Lett. 2006 Aug 15;16(16):4360-5. doi: 10.1016/j.bmcl.2006.05.050.
Mark Sabat 1,  John C Vanrens,  Michael P Clark,  Todd A Brugel,  Jennifer Maier,  Roger G Bookland,  Matthew J Laufersweiler,  Steven K Laughlin,  Adam Golebiowski,  Biswanath De,  Lily C Hsieh,  Richard L Walter,  Marlene J Mekel,  Michael J Janusz
Affiliations

Affiliation

  • 1 Procter and Gamble Pharmaceuticals, Health Care Research Center, Mason, OH 45040, USA. [email protected]
PMID: 16750367 DOI: 10.1016/j.bmcl.2006.05.050
Abstract

A series of C-2, C-8, and N-9 trisubstituted purine based inhibitors of TNF-alpha production are described. The most potent analogs showed low nanomolar activity against LPS-induced TNF-alpha production in a THP-1 cell based assay. The SAR of the series was optimized with the aid of X-ray co-crystal structures of these inhibitors bound with mutated p38 (mp38).

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