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

@article{Hilfiker2013OptimizationOA,
  title={Optimization of a Novel Series of TRPV4 Antagonists with In Vivo Activity in a Model of Pulmonary Edema.},
  author={Mark A. Hilfiker and Tram H Hoang and Johan Cornil and Hilary Schenck Eidam and Daniel S Matasic and Theresa J Roethke and Michael D. Klein and Kevin S. Thorneloe and Mui Cheung},
  journal={ACS medicinal chemistry letters},
  year={2013},
  volume={4 2},
  pages={293-6}
}
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. 
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