TRPV4 is a member of the Transient Receptor Potential (TRP) superfamily of cation channels which is expressed in the lung and regulates the integrity of the alveolar septal barrier.  Increased pulmonary vascular pressure evokes TRPV4-dependent pulmonary edema; therefore, inhibition of TRPV4 represents a novel approach for the treatment of pulmonary edema associated with congestive heart failure.  3-(1,4'-Bipiperidin-1'-ylmethyl)-7-bromo-N-(1-phenylcyclopropyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxamide (GSK2193874) is an orally active, potent and selective TRPV4 blocker. Our approaches leading to the discovery of GSK2193874 and its pharmacokinetic properties and biological profiles will be discussed.

Discovery of GSK2193874: An orally active, potent and selective blocker of the transient receptor potential vanilloid 4

247th National Meeting (2014)

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