| Literature DB >> 19010673 |
Craig A Stump1, 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.
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.Entities:
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Year: 2008 PMID： 19010673 DOI： 10.1016/j.bmcl.2008.10.106
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823