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Optimization of a Novel Series of TRPV4 Antagonists with In Vivo Activity in a Model of Pulmonary Edema.

ABSTRACT: High-throughput screening and subsequent hit optimization identified 1-piperidinylbenzimidazoles, exemplified by compound 1, as TRPV4 inhibitors. Lead optimization identified potent TRPV4 blocker 19, which has good target activity and pharmacokinetic properties. Inhibitor 19 was then profiled in an in vivo rat model, demonstrating its ability to inhibit TRPV4-mediated pulmonary edema.

SUBMITTER: Hilfiker MA 

PROVIDER: S-EPMC4027501 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Optimization of a Novel Series of TRPV4 Antagonists with In Vivo Activity in a Model of Pulmonary Edema.

Hilfiker Mark A MA   Hoang Tram H TH   Cornil Johan J   Eidam Hilary S HS   Matasic Daniel S DS   Roethke Theresa J TJ   Klein Michael M   Thorneloe Kevin S KS   Cheung Mui M  

ACS medicinal chemistry letters 20130127 2

High-throughput screening and subsequent hit optimization identified 1-piperidinylbenzimidazoles, exemplified by compound 1, as TRPV4 inhibitors. Lead optimization identified potent TRPV4 blocker 19, which has good target activity and pharmacokinetic properties. Inhibitor 19 was then profiled in an in vivo rat model, demonstrating its ability to inhibit TRPV4-mediated pulmonary edema. ...[more]

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