Identification and hit-to-lead exploration of a novel series of histamine H4 receptor inverse agonists

  • Bioorg Med Chem Lett. 2010 Apr 15;20(8):2516-9. doi: 10.1016/j.bmcl.2010.02.097.
Sue Cramp  1 ,  Hazel J Dyke ,  Christopher Higgs ,  David E Clark ,  Matthew Gill ,  Pascal Savy ,  Neil Jennings ,  Steve Price ,  Peter M Lockey ,  Dennis Norman ,  Soraya Porres ,  Francis Wilson ,  Alison Jones ,  Nigel Ramsden ,  Raffaella Mangano ,  Dan Leggate ,  Marie Andersson ,  Richard Hale
Affiliations
PMID: 20299215 DOI: 10.1016/j.bmcl.2010.02.097
Abstract

The identification and hit-to-lead exploration of a novel, potent and selective series of histamine H(4) receptor inverse agonists is described. The initial hit, 3A (IC(50) 19 nM) was identified by means of a ligand-based virtual screening approach. Subsequent medicinal chemistry exploration yielded 18I which possessed increased potency (R-enantiomer IC(50) 1 nM) as well as enhanced microsomal stability.

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