Serendipitous oxidation product of BIBN4096BS: a potent CGRP receptor antagonist

Bioorg Med Chem Lett. 2014 Jun 15;24(12):2744-8. doi: 10.1016/j.bmcl.2014.04.033. Epub 2014 Apr 18.

Abstract

An oxidation product (5) formed during the synthesis of BIBN-4096BS (1) was found to be a potent CGRP antagonist (IC50=0.11nM). While 5 was found to be ten-fold less potent than 1, another analog 8 with lower molecular weight containing the oxidized fragment demonstrated twenty-fold higher activity than its parent 7. Alternative conditions which preclude the formation of the oxidation product are described. The activities of 1, 5, 7 and 8 in functional cAMP assay are also discussed.

Keywords: Antagonists; BIBN4096BS; CGRP.

MeSH terms

  • Biological Assay
  • Calcitonin Gene-Related Peptide Receptor Antagonists*
  • Inhibitory Concentration 50
  • Molecular Structure
  • Oxidation-Reduction
  • Piperazines / chemical synthesis
  • Piperazines / chemistry*
  • Piperazines / pharmacology
  • Quinazolines / chemical synthesis
  • Quinazolines / chemistry*
  • Quinazolines / pharmacology

Substances

  • Calcitonin Gene-Related Peptide Receptor Antagonists
  • Piperazines
  • Quinazolines
  • olcegepant