Identification of 1S,2R-milnacipran analogs as potent norepinephrine and serotonin transporter inhibitors

A series of milnacipran analogs were synthesized and studied as monoamine transporter inhibitors, and several potent compounds with moderate lipophilicity were identified from the 1S,2R-isomers. Thus, 15l exhibited IC50 values of 1.7 nM at NET and 25 nM at SERT, which were, respectively, 20- and 13-fold more potent than 1S,2R-milnacipran 1–II.

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