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-oxabicyclo[3.1.0]hexane and those with the 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-[(diethylamino)carbonyl]-2- (aminomethyl)cyclopropane hydrochloride, midalcipran (INN), was selected for further development. This compound is currently in phase III clinical evaluation.
D000596:Amino Acids / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D000928:Antidepressive Agents / Q000138:chemical synthesis*; D001522:Behavior, Animal / Q000187:drug effects; D001763:Blepharoptosis / Q000188:drug therapy; D003521:Cyclopropanes / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship; D015016:Yohimbine / Q000037:antagonists & inhibitors / Q000633:toxicity
D000596:Amino Acids; D000928:Antidepressive Agents; D003521:Cyclopropanes; D007202:Indicators and Reagents; D015016:Yohimbine