Novel small molecule bradykinin B1 receptor antagonists. Part 1: Benzamides and semicarbazides

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 aci...

Full description

Saved in:
Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2010-02, Vol.20 (3), p.1225-1228
Main Authors: SCHAUDT, Marco, LOCARDI, Elsa, SCHNATBAUM, Karsten, ZISCHINSKY, Gunther, STRAGIES, Roland, PFEIFER, Jochen R, GIBSON, Christoph, SCHARN, Dirk, RICHTER, Uwe, KALKHOF, Holger, DINKEL, Klaus
Format: Article
Language:English
Subjects:
Animals
Benzamides - chemistry
Benzamides - metabolism
Benzamides - pharmacology
Biological and medical sciences
Bradykinin B1 Receptor Antagonists
Caco-2 Cells
Humans
Male
Medical sciences
Microsomes - drug effects
Microsomes - metabolism
Neuropharmacology
Neurotransmitters. Neurotransmission. Receptors
Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems
Pharmacology. Drug treatments
Rats
Rats, Wistar
Receptor, Bradykinin B1 - metabolism
Semicarbazides - chemistry
Semicarbazides - metabolism
Semicarbazides - pharmacology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2009.11.119