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ID: ALA1933038

Journal: Bioorg Med Chem Lett

Title: Ligand based design of novel histamine H₄ receptor antagonists; fragment optimization and analysis of binding kinetics.

Authors: Smits RA, Lim HD, van der Meer T, Kuhne S, Bessembinder K, Zuiderveld OP, Wijtmans M, de Esch IJ, Leurs R.

Abstract: The histamine H(4) receptor is a G protein-coupled receptor that has attracted much interest for its role in inflammatory and immunomodulatory functions. In our search for new H(4)R ligands, a low affinity isoquinoline fragment was optimized to 7-(furan-2-yl)-4-(piperazin-1-yl)quinazolin-2-amine (VUF11489), as a new H(4)R antagonist. Analysis of its binding kinetics at the human H(4)R showed this compound to have a very different dissociative half-life in comparison with reference antagonist JNJ7777120.

CiteXplore: 22153663

DOI: 10.1016/j.bmcl.2011.10.104