{"id":2412,"date":"2018-03-27T13:45:44","date_gmt":"2018-03-27T13:45:44","guid":{"rendered":"https:\/\/www.sygnaturediscovery.com\/journal-paper\/1h-pyrazolo34-ghexahydro-isoquinolines\/"},"modified":"2018-03-27T13:45:44","modified_gmt":"2018-03-27T13:45:44","slug":"1h-pyrazolo34-ghexahydro-isoquinolines","status":"publish","type":"journal-paper","link":"https:\/\/www.sygnaturediscovery.com\/fr\/journal-paper\/1h-pyrazolo34-ghexahydro-isoquinolines\/","title":{"rendered":"1H-Pyrazolo[3,4-g]hexahydro-isoquinolines as potent GR antagonists with reduced hERG inhibition and an improved pharmacokinetic profile"},"content":{"rendered":"

Hunt, H. J., Belanoff, J.K., Golding, E., Gourdet, B., Phillips, T., Swift, D., Thomas, J.,\u00a0Unitt, J.F., Walters, I.<\/p>\n

Abstract<\/strong><\/p>\n

\n

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.<\/p>\n

Ref:\u00a0<\/strong>Bioorg Med Chem Lett. 2015 Dec 15;25(24):5720-5<\/p>\n<\/div>\n

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