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Bioorg Med Chem Lett. 2010 Apr 15;20(8):2572-6. doi: 10.1016/j.bmcl.2010.02.086. Epub 2010 Feb 25.

Identification of potent, highly constrained CGRP receptor antagonists.

Author information

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

Abstract

A novel series of potent CGRP receptor antagonists containing a central quinoline ring constraint was identified. The combination of the quinoline constraint with a tricyclic benzimidazolinone left hand fragment produced an analog with picomolar potency (14, CGRP K(i)=23 pM). Further optimization of the tricycle produced a CGRP receptor antagonist that exhibited subnanomolar potency (19, CGRP K(i)=0.52 nM) and displayed a good pharmacokinetic profile in three preclinical species.

PMID:
20299218
DOI:
10.1016/j.bmcl.2010.02.086
[Indexed for MEDLINE]

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