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Bioorg Med Chem Lett. 2009 Jan 1;19(1):214-7. doi: 10.1016/j.bmcl.2008.10.106. Epub 2008 Oct 31.

The discovery of highly potent CGRP receptor antagonists.

Author information

1
Department of Medicinal Chemistry, Merck & Co, Inc, West Point, PA 19486, USA. craig_stump@merck.com

Abstract

Rational modification of a previously identified spirohydantoin lead structure has identified a series of potent spiroazaoxindole CGRP receptor antagonists. The azaoxindole was found to be a general replacement for the hydantoin that consistently improved in vitro potency. The combination of the indanylspiroazaoxindole and optimized benzimidazolinones led to highly potent antagonists (e.g., 25, CGRP K(i)=40pM). The closely related compound 27 demonstrated good oral bioavailability in dog and rhesus.

PMID:
19010673
DOI:
10.1016/j.bmcl.2008.10.106
[Indexed for MEDLINE]

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