1H-Pyrazolo[3,4-g]hexahydro-isoquinolines as potent GR antagonists with reduced hERG inhibition and an improved pharmacokinetic profile.
Basic Information
ID: ALA3734698
Journal: Bioorg Med Chem Lett
Title: 1H-Pyrazolo[3,4-g]hexahydro-isoquinolines as potent GR antagonists with reduced hERG inhibition and an improved pharmacokinetic profile.
Authors: Hunt HJ, Belanoff JK, Golding E, Gourdet B, Phillips T, Swift D, Thomas J, Unitt JF, Walters I.
Abstract: We report the further optimization of our series 1H-pyrazolo[3,4-g]hexahydro-isoquinoline sulfonamides as GR antagonists. By incorporating a heteroaryl ketone group at the ring junction, we have obtained compounds with excellent functional GR antagonism. Optimization of the sulfonamide substituent has provided compounds with a very desirable overall profile, including minimal hERG activity, good bioavailability and in vivo efficacy.
CiteXplore: 26546213
DOI: 10.1016/j.bmcl.2015.10.097
Patent ID: ┄