Identification of a novel RAMP-independent CGRP receptor antagonist

Bioorg Med Chem Lett. 2011 Nov 15;21(22):6705-8. doi: 10.1016/j.bmcl.2011.09.056. Epub 2011 Sep 21.


Identification of an HIV integrase inhibitor with micromolar affinity for the CGRP receptor led to the discovery of a series of structurally novel CGRP receptor antagonists. Optimization of this series produced compound 16, a low-molecular weight CGRP receptor antagonist with good pharmacokinetic properties in both rat and dog. In contrast to other nonpeptide antagonists, the activity of 16 was affected by the presence of divalent cations and showed evidence of an alternative, RAMP-independent CGRP receptor binding site.

MeSH terms

  • Animals
  • Calcitonin Gene-Related Peptide Receptor Antagonists*
  • Cell Line
  • Dogs
  • HIV / enzymology
  • HIV Integrase Inhibitors / chemistry*
  • HIV Integrase Inhibitors / pharmacokinetics
  • HIV Integrase Inhibitors / pharmacology*
  • Humans
  • Protein Binding
  • Pyridines / chemistry*
  • Pyridines / pharmacokinetics
  • Pyridines / pharmacology*
  • Rats
  • Receptor Activity-Modifying Proteins / metabolism*
  • Receptors, Calcitonin Gene-Related Peptide / metabolism*


  • Calcitonin Gene-Related Peptide Receptor Antagonists
  • HIV Integrase Inhibitors
  • Pyridines
  • Receptor Activity-Modifying Proteins
  • Receptors, Calcitonin Gene-Related Peptide
  • hydroxypyridines