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

Basic Information

ID: ALA1156992

Journal: Bioorg Med Chem Lett

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

Authors: 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, Hale R.

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.

CiteXplore: 20299215

DOI: 10.1016/j.bmcl.2010.02.097

Patent ID: