The synthesis and biological activity of pentafluorosulfanyl analogs of fluoxetine, fenfluramine, and norfenfluramine

The trifluoromethyl group of fluoxetine 1 and fenfluramine and norfenfluramine, 2 and 3, was substituted by the pentafluorosulfanyl group. On examination of the efficacy of the pentafluorosulfanyl containing compounds as inhibitors of 5-hydroxytryptamine receptors, it was found that substitution could lead to enhanced selectivity and in the case of the pentafluorosulfanyl analog of fenfluramine, 18, it significantly enhanced potency against the 5-HT2b, 5-HT2c, and 5-HT6 receptors.

The affinity of the pentafluorosulfanyl analogs of fluoxetine, fenfluramine, and norfenfluramine for a panel of 5-HT receptors has been determined. The affinity of the analogs is compared and contrasted with that of the parent compounds.Figure optionsDownload as PowerPoint slide