Studies on the SAR and pharmacophore of milnacipran derivatives as monoamine transporter inhibitors

Derivatives of milnacipran were synthesized and studied as monoamine transporter inhibitors. Potent analogs were discovered at NET (9k) and at both NET and SERT (9s and 9u). A pharmacophore model was established based on the conformational analysis of milnacipran in aqueous solution using NMR techniques and was consistent with the SAR results. (c) 2008 Elsevier Ltd. All rights reserved.