Calcitonin gene-related peptide (CGRP) receptor antagonists: investigations of a pyridinone template

Bioorg Med Chem Lett. 2008 Jan 15;18(2):755-8. doi: 10.1016/j.bmcl.2007.11.042. Epub 2007 Nov 17.

Abstract

In our effort to find potent, orally bioavailable CGRP receptor antagonists for the treatment of migraine, a novel series based on a pyridinone template was investigated. After optimizing the privileged structure and the placement of the attached phenyl ring, systematic SAR was carried out on both the N-alkyl and C-5 aryl substituents. Several analogs with good potency and pharmacokinetic profiles were identified.

MeSH terms

  • Administration, Oral
  • Animals
  • Biological Availability
  • Calcitonin Gene-Related Peptide Receptor Antagonists*
  • Half-Life
  • Pyridones / administration & dosage
  • Pyridones / chemistry
  • Pyridones / pharmacokinetics
  • Pyridones / pharmacology*
  • Rats
  • Structure-Activity Relationship

Substances

  • Calcitonin Gene-Related Peptide Receptor Antagonists
  • Pyridones