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

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.

• Authors: Diem N Nguyen, Daniel V Paone, Anthony W Shaw, Christopher S Burgey, Scott D Mosser, Victor Johnston, Christopher A Salvatore, Yvonne M Leonard, Cynthia M Miller-Stein, Stefanie A Kane, Kenneth S Koblan, Joseph P Vacca, Samuel L Graham, Theresa M Williams
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 18 Issue 2 Pg. 755-8 (Jan 15 2008) ISSN: 1464-3405 [Electronic] England
• PMID: 18039571 (Publication Type: Journal Article)

Chemical References

• Calcitonin Gene-Related Peptide Receptor Antagonists
• Pyridones

Topics

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