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Identification and hit-to-lead exploration of a novel series of histamine H4 receptor inverse agonists |
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| Authors: | Sue Cramp 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 |
| Institution: | 1. Argenta, 8/9 Spire Green Centre, Flex Meadow, Harlow, Essex, CM19 5TR, UK;2. Cellzome Ltd, Chesterford Research Park, Little Chesterford, Cambridge, CB10 1XL, UK |
| Abstract: | The identification and hit-to-lead exploration of a novel, potent and selective series of histamine H4 receptor inverse agonists is described. The initial hit, 3A (IC50 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 IC50 1 nM) as well as enhanced microsomal stability. |
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