Novel small molecule bradykinin B1 receptor antagonists. Part 1: benzamides and semicarbazides.
Marco Schaudt, Elsa Locardi, Gunther Zischinsky, Roland Stragies, Jochen R Pfeifer, Christoph Gibson, Dirk Scharn, Uwe Richter, Holger Kalkhof, Klaus Dinkel, Karsten Schnatbaum
Index: Bioorg. Med. Chem. Lett. 20(3) , 1225-8, (2010)
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Abstract
The synthesis and SAR of two series of bradykinin B(1) receptor antagonists is described. The benzamide moiety proved to be a suitable replacement for the aryl ester functionality of biaryl based antagonists. In addition, it was found that semicarbazides can effectively replace cyclopropyl amino acids. The compounds with the best overall profile were biaryl semicarbazides which display high antagonistic activity, low Caco-2 efflux and high oral bioavailability in the rat.Copyright (c) 2009 Elsevier Ltd. All rights reserved.