1. Identification and hit-to-lead exploration of a novel series of histamine H4 receptor inverse agonists.
- Author
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Cramp S, Dyke HJ, Higgs C, Clark DE, Gill M, Savy P, Jennings N, Price S, Lockey PM, Norman D, Porres S, Wilson F, Jones A, Ramsden N, Mangano R, Leggate D, Andersson M, and Hale R
- Subjects
- Animals, Biological Availability, Drug Discovery, Histamine Antagonists chemistry, Histamine Antagonists pharmacokinetics, Inhibitory Concentration 50, Macaca fascicularis, Rats, Receptors, Histamine, Receptors, Histamine H4, Stereoisomerism, Histamine Antagonists pharmacology, Receptors, G-Protein-Coupled antagonists & inhibitors
- 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., (Copyright 2010 Elsevier Ltd. All rights reserved.)
- Published
- 2010
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