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 mil
1-Aryl-2-(aminomethyl)cyclopropanecarboxylic Acid Derivatives. A New Series of Potential Antidepressants
A series of 1-aryl-2-(aminomethyl)cyclopropanecarboxylic acid derivatives were synthesized and evaluated as potential antidepressants.Compounds with the Z configuration were synthesized from 1-aryl-2-oxo-3-oxabicyclohexane and those with E configuration from (E)-1-phenyl-2-(hydroxymethyl)cyclopropanecarboxylic acid.The compounds were evaluated in animal tests designed to reveal potential antidepressant activity and the existence of undesirable side effects.Several derivatives were more active than imipramine and desipramine.On the basis of its activity in pharmacological animal tests of antidepressant activity and its potential lack of side effects, 1-phenyl-1--2-(aminomethyl)cyclopropane hydrochloride, midalcipran (INN), was selected for further development.This compound is currently in phase III clinical evaluation.