Design, Molecular Docking, Synthesis and Antidepressant Activity of Moclobemide Derivatives

OBJECTIVE To synthesis 6 novel morpholino derivatives and study their pharmacological activity.

METHODS Based on moclobemide as the lead compound, the derivatives with good binding activity were designed and screened using molecular docking technique. Six novel compounds were synthesized by amination, Leuckart-wallach reduction, acidification and acylation reactions using brominated aryl acetone, aminopropanol and aryl carbonyl chloride as raw materials, and the target compounds were investigated for antidepressant activity using forced swimming assay in mice.

RESULTS The target compounds were structurally verified by ¹H-NMR, ¹³C-NMR, IR and MS, and the forced swimming immobility time in mice for compounds 5a and 5b was (56.8±15.2)s and (47.2±13.1)s, respectively, which was significantly lower than that of the blank control (154.6±37.2)s(P<0.05), and was comparable to the forced swimming immobility time in mice for morpholino (45.7±12.7)s comparable.

CONCLUSION The synthetic route has mild and easy reaction conditions, and the target compounds 5a and 5b show good antidepressant activity.