Format

Send to

Choose Destination
Bioorg Med Chem Lett. 2007 Sep 1;17(17):4795-8. Epub 2007 Jun 26.

Caprolactams as potent CGRP receptor antagonists for the treatment of migraine.

Author information

1
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. anthony_shaw@merck.com

Abstract

Calcitonin gene-related peptide (CGRP) has been implicated in the pathogenesis of migraine. Replacements for the benzodiazepine core of an earlier lead structure 1 including 5-, 6-, and 7-membered lactams were explored. Within the 7-membered ring scaffold, phenyl substitution at various positions afforded the potent (3R)-amino-(6S)-phenyl caprolactam template. The phenylimidazolinone privileged structure gave additional potency enhancements, as 24 showed good potency in both CGRP binding (K(i)=2 nM) and cAMP (IC(50)=4 nM) assays and was orally bioavailable in rats (27%).

PMID:
17616394
DOI:
10.1016/j.bmcl.2007.06.062
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center