The identification of clinical candidate SB-480848: a potent inhibitor of lipoprotein-associated phospholipase A2

  • Bioorg Med Chem Lett. 2003 Mar 24;13(6):1067-70. doi: 10.1016/s0960-894x(03)00058-1.
Josie A Blackie  1 ,  Jackie C Bloomer ,  Murray J B Brown ,  Hung Yuan Cheng ,  Beverley Hammond ,  Deirdre M B Hickey ,  Robert J Ife ,  Colin A Leach ,  V Ann Lewis ,  Colin H Macphee ,  Kevin J Milliner ,  Kitty E Moores ,  Ivan L Pinto ,  Stephen A Smith ,  Ian G Stansfield ,  Steven J Stanway ,  Maxine A Taylor ,  Colin J Theobald
Affiliations
  • 1. Medicines Research Centre, GlaxoSmithKline, Gunnels Wood Road, Stevenage SG1 2NY, UK.
PMID: 12643913 DOI: 10.1016/s0960-894x(03)00058-1
Abstract

Modification of the pyrimidone 5-substituent in clinical candidate SB-435495 has given a series of inhibitors of recombinant lipoprotein-associated Phospholipase A(2) with sub-nanomolar potency. Cyclopentyl fused derivative 21, SB-480848, showed an enhanced in vitro and in vivo profile versus SB-435495 and has been selected for progression to man.

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