The discovery of SB-435495. A potent, orally active inhibitor of lipoprotein-associated phospholipase A(2) for evaluation in man

  • Bioorg Med Chem Lett. 2002 Sep 16;12(18):2603-6. doi: 10.1016/s0960-894x(02)00473-0.
Josie A Blackie  1 ,  Jackie C Bloomer ,  Murray J B Brown ,  Hung-Yuan Cheng ,  Richard L Elliott ,  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 ,  Caroline M Whittaker
Affiliations
  • 1. GlaxoSmithKline, Medicines Research Centre, Gunnels Wood Road, SG1 2NY, Stevenage, UK.
PMID: 12182870 DOI: 10.1016/s0960-894x(02)00473-0
Abstract

The introduction of a functionalised amido substituent into a series of 1-(biphenylmethylacetamido)-pyrimidones has given a series of inhibitors of recombinant lipoprotein-associated Phospholipase A(2) with sub-nanomolar potency and very encouraging developability properties. Diethylaminoethyl derivative 32, SB-435495, was selected for progression to man.

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