Substituted urea derivatives: a potent class of antidepressant agents

A series of fourteen (14) N-nitrophenyl-N'-(alkyl/aryl)urea and symmetrical 1,3-disubstituted urea derivatives were synthesized and evaluated for their antidepressant activity in mice. Among them, N-(4-nitrophenyl)-N'-(1'-phenylethyl)urea (1), demonstrated profound antidepressant property as reflected by significant reduction in the immobility time (89.83%), whereas compounds 2-6 showed activity values between 36 to 59% which were also larger than the standard phenelzine. Compounds 7-9 were less effective in reducing the immobility period of mice 26.20 to 31.01%). This variable magnitude of antidepressant activity appears to be related to the position of the nitro group to the parent molecules 1, 2, and 8. Compound 1 with the nitro group at para position showed to be the most effective antidepressant. However, the activity declined, if the nitro is attached to ortho and meta positions.