Caprolactams as potent CGRP receptor antagonists for the treatment of migraine.
Bioorg Med Chem Lett
; 17(17): 4795-8, 2007 Sep 01.
Article
em En
| MEDLINE
| ID: mdl-17616394
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%).
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Caprolactama
/
Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina
/
Transtornos de Enxaqueca
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Estados Unidos