The identification of potent, orally bioavailable tricyclic CGRP receptor antagonists

  • Bioorg Med Chem Lett. 2009 Aug 15;19(16):4740-2. doi: 10.1016/j.bmcl.2009.06.057.
Ian M Bell  1 ,  Rodney A Bednar ,  Halea A Corcoran ,  John F Fay ,  Steven N Gallicchio ,  Victor K Johnston ,  James C Hershey ,  Cynthia M Miller-Stein ,  Eric L Moore ,  Scott D Mosser ,  Shane A Roller ,  Christopher A Salvatore ,  Cory R Theberge ,  Bradley K Wong ,  C Blair Zartman ,  Stefanie A Kane ,  Theresa M Williams ,  Samuel L Graham ,  Joseph P Vacca
Affiliations
  • 1. Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. [email protected]
PMID: 19577468 DOI: 10.1016/j.bmcl.2009.06.057
Abstract

A series of tricyclic CGRP Receptor antagonists was optimized in order to improve oral bioavailability. Attenuation of polar surface area and incorporation of a weakly basic indoline nitrogen led to compound 5, a potent antagonist with good oral bioavailability in three species.