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Identification of orally-bioavailable antagonists of the TRPV4 ion-channel.

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.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Wei ZL,Nguyen MT,O'Mahony DJ,Acevedo A,Zipfel S,Zhang Q,Liu L,Dourado M,Chi C,Yip V,DeFalco J,Gustafson A,Emerling DE,Kelly MG,Kincaid J,Vincent F,Duncton MA

doi

10.1016/j.bmcl.2015.06.098

subject

Has Abstract

pub_date

2015-09-15 00:00:00

pages

4011-5

issue

18

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(15)00703-9

journal_volume

25

pub_type

杂志文章

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