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Bioorg Med Chem Lett. 2008 Jul 1;18(13):3716-9. doi: 10.1016/j.bmcl.2008.05.058. Epub 2008 May 20.

Potent and selective small-molecule human urotensin-II antagonists with improved pharmacokinetic profiles.

Author information

1
Department of Medicinal Chemistry, Cardiovascular and Urogenital Center of Excellence for Drug Discovery, GlaxoSmithKline Pharmaceuticals, 709 Swedeland Road, PO Box 1539, King of Prussia, PA 19406, USA. jeff.j.mcatee@gsk.com

Abstract

Lead compound 1 was successfully redesigned to provide compounds with improved pharmacokinetic profiles for this series of human urotensin-II antagonists. Replacement of the 2-pyrrolidinylmethyl-3-phenyl-piperidine core of 1 with a substituted N-methyl-2-(1-pyrrolidinyl)ethanamine core as in compound 7 resulted in compounds with improved oral bioavailability in rats. The relationship between stereochemistry and selectivity for hUT over the kappa-opioid receptor was also explored.

PMID:
18524591
DOI:
10.1016/j.bmcl.2008.05.058
[Indexed for MEDLINE]

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