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Bioorg Med Chem Lett. 2011 May 1;21(9):2683-6. doi: 10.1016/j.bmcl.2010.12.054. Epub 2010 Dec 30.

Orally bioavailable imidazoazepanes as calcitonin gene-related peptide (CGRP) receptor antagonists: discovery of MK-2918.

Author information

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

Abstract

In our ongoing efforts to develop CGRP receptor antagonists for the treatment of migraine, we aimed to improve upon telecagepant by targeting a compound with a lower projected clinical dose. Imidazoazepanes were identified as potent caprolactam replacements and SAR of the imidazole yielded the tertiary methyl ether as an optimal substituent for potency and hERG selectivity. Combination with the azabenzoxazinone spiropiperidine ultimately led to preclinical candidate 30 (MK-2918).

PMID:
21251825
DOI:
10.1016/j.bmcl.2010.12.054
[Indexed for MEDLINE]

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