2. Academic Validation
  3. The discovery of highly potent CGRP receptor antagonists

The discovery of highly potent CGRP receptor antagonists

  • Bioorg Med Chem Lett. 2009 Jan 1;19(1):214-7. doi: 10.1016/j.bmcl.2008.10.106.
Craig A Stump 1,  Ian M Bell,  Rodney A Bednar,  Joseph G Bruno,  John F Fay,  Steven N Gallicchio,  Victor K Johnston,  Eric L Moore,  Scott D Mosser,  Amy G Quigley,  Christopher A Salvatore,  Cory R Theberge,  C Blair Zartman,  Xu-Fang Zhang,  Stefanie A Kane,  Samuel L Graham,  Joseph P Vacca,  Theresa M Williams
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, Merck & Co, Inc, West Point, PA 19486, USA. [email protected]
PMID: 19010673 DOI: 10.1016/j.bmcl.2008.10.106
Abstract

Rational modification of a previously identified spirohydantoin lead structure has identified a series of potent spiroazaoxindole CGRP Receptor antagonists. The azaoxindole was found to be a general replacement for the hydantoin that consistently improved in vitro potency. The combination of the indanylspiroazaoxindole and optimized benzimidazolinones led to highly potent antagonists (e.g., 25, CGRP K(i)=40pM). The closely related compound 27 demonstrated good oral bioavailability in dog and rhesus.

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