| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1358741 | Bioorganic & Medicinal Chemistry Letters | 2015 | 5 Pages |
Abstract
Antagonists of the TRPV4 receptor were identified using a focused screen, followed by a limited optimization program. The leading compounds obtained from this exercise, RN-1665 23 and RN-9893 26, showed moderate oral bioavailability when dosed to rats. The lead molecule, RN-9893 26, inhibited human, rat and murine variants of TRPV4, and showed excellent selectivity over related TRP receptors, such as TRPV1, TRPV3 and TRPM8. The overall profile for RN-9893 may permit its use as a proof-of-concept probe for in vivo applications.
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Zhi-Liang Wei, Margaret T. Nguyen, Donogh J.R. O’Mahony, Alejandra Acevedo, Sheila Zipfel, Qingling Zhang, Luna Liu, Michelle Dourado, Candace Chi, Victor Yip, Jeff DeFalco, Amy Gustafson, Daniel E. Emerling, Michael G. Kelly, John Kincaid,