Chiral tetrahydroquinoline derivatives as potent anti-hyperalgesic agents in animal models of sustained inflammation and chronic neuropathic pain |
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Authors: | Di Fabio Romano Alvaro Giuseppe Bertani Barbara Donati Daniele Pizzi Domenica Maria Gentile Gabriella Pentassuglia Giorgio Giacobbe Simone Spada Simone Ratti Emiliangelo Corsi Mauro Quartaroli Mauro Barnaby Robert J Vitulli Giovanni |
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Institution: | GlaxoSmithKline Medicines Research Centre, Via A. Fleming 4, 37135 Verona, Italy. rdf26781@gsk.com |
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Abstract: | Chiral tetrahydroquinoline derivatives have been prepared by an asymmetric Mannich-type condensation reaction using commercially available vinyloxyethylsilane and a N-arylimino R-(+)-t-butyl lactate ester, in the presence of a catalytic amount of metal triflates as Lewis acids. This synthetic approach gave rise to the target aldehyde intermediate in moderate facial diastereoselectivity and in high chemical yield. This efficient route enabled to scale up the synthesis of an orally bioavailable glycine antagonist showing outstanding in vivo anti-hyperalgesic activity in different animal models of sustained inflammation and chronic neuropathic pain. |
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