Novel small molecule bradykinin B1 receptor antagonists. Part 3: hydroxyurea derivatives

Karsten Schnatbaum; Marco Schaudt; Roland Stragies; Jochen R Pfeifer; Christoph Gibson; Elsa Locardi; Dirk Scharn; Uwe Richter; Holger Kalkhof; Klaus Dinkel; Gunther Zischinsky

doi:10.1016/j.bmcl.2009.11.121

Novel small molecule bradykinin B1 receptor antagonists. Part 3: hydroxyurea derivatives

Bioorg Med Chem Lett. 2010 Feb 1;20(3):1233-6. doi: 10.1016/j.bmcl.2009.11.121. Epub 2009 Dec 2.

Authors

Karsten Schnatbaum¹, Marco Schaudt, Roland Stragies, Jochen R Pfeifer, Christoph Gibson, Elsa Locardi, Dirk Scharn, Uwe Richter, Holger Kalkhof, Klaus Dinkel, Gunther Zischinsky

Affiliation

¹ Jerini AG, Invalidenstrasse 130, 10115 Berlin, Germany.

PMID: 20036120
DOI: 10.1016/j.bmcl.2009.11.121

Abstract

Hydroxy urea moieties are introduced as a new class of bradykinin B(1) receptor antagonists. First, the SAR of the lead compound was systematically explored. Subsequent optimization resulted in the identification of several biaryl-based hydroxyurea bradykinin B(1) receptor antagonists with low-nanomolar activity and very high oral bioavailability in the rat.

Publication types

Comparative Study

MeSH terms

Animals
Biological Availability
Bradykinin B1 Receptor Antagonists*
Caco-2 Cells
Fibroblasts / drug effects
Fibroblasts / metabolism
Humans
Hydroxyurea / administration & dosage
Hydroxyurea / chemistry*
Hydroxyurea / metabolism*
Male
Protein Binding / drug effects
Rats
Rats, Wistar
Receptor, Bradykinin B1 / metabolism*

Substances

Bradykinin B1 Receptor Antagonists
Receptor, Bradykinin B1
Hydroxyurea