| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1364353 | Bioorganic & Medicinal Chemistry Letters | 2008 | 4 Pages |
Abstract
The previously disclosed spirohydantoin-based CGRP receptor antagonists were optimized for potency through modification of the benzimidazolone substituents. Compounds were identified which had minimal shift in the cAMP functional assay containing 50% human serum. Blockade of CGRP-mediated vasodilation was observed with these compounds in a rhesus pharmacodynamic assay and the in vivo potency correlated with the in vitro activity in the serum-shifted functional assay.
Graphical abstractElaboration of the benzimidazolone core of spirohydantoin CGRP receptor antagonists is described.Figure optionsDownload full-size imageDownload as PowerPoint slide
Related Topics
Physical Sciences and Engineering
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Authors
Cory R. Theberge, Rodney A. Bednar, Ian M. Bell, Halea A. Corcoran, John F. Fay, James C. Hershey, Victor K. Johnston, Stefanie A. Kane, Scott Mosser, Christopher A. Salvatore, Theresa M. Williams, C. Blair Zartman, Xu-Fang Zhang, Samuel L. Graham,