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-HT(2b), 5-HT(2c), and 5-HT(6) receptors.
Welch
John T
JT
Department of Chemistry, University at Albany, SUNY, Albany, NY 12222, USA. jwelch@uamail.albany.edu
Lim
Dong Sung
DS
D000818:Animals; D005277:Fenfluramine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D005473:Fluoxetine / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D009642:Norfenfluramine / Q000737:chemistry / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects*; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D005277:Fenfluramine; D005473:Fluoxetine; D009642:Norfenfluramine; D011985:Receptors, Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; C525224:1-(3-(pentafluorosulfanyl)phenyl)propan-2-amine; C525225:N-ethyl-1-(3-(pentafluorosulfanyl)phenyl)propan-2-amine