Ligand based design of novel histamine H 4 receptor antagonists; fragment optimization and analysis of binding kinetics

…, T van der Meer, S Kuhne, K Bessembinder…

Index: Smits, Rogier A.; Lim, Herman D.; Van Der Meer, Tiffany; Kuhne, Sebastiaan; Bessembinder, Karin; Zuiderveld, Obbe P.; Wijtmans, Maikel; De Esch, Iwan J.P.; Leurs, Rob Bioorganic and Medicinal Chemistry Letters, 2012 , vol. 22, # 1 p. 461 - 467

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Citation Number: 25

Abstract

The histamine H4 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 H4R ligands, a low affinity isoquinoline fragment was optimized to 7-(furan-2-yl)-4-(piperazin-1-yl) quinazolin-2-amine (VUF11489), as a new H4R antagonist. Analysis of its binding kinetics at the human H4R showed this compound to have a very different dissociative half-life in ...