Three Schiff bases of Mannich bases of resacetophenone have been synthesised by using three variable electronegative atoms (X=O/S/NH) of urea/thiourea/guanidine and tested for CNS depressant activity. It has been found that Compound-3c (X=NH) showed maximum CNS depressant effect in the Albino mice and producing more sedative effect and more sleeping time, Compound-3a (X=O) showed less sleeping time than guanidine derivative. There is very less effect compared to both very less sedative effect in the case of Compound-3b (X=S). CNS depressant activity profile of three compounds is as follows: Compounds: 3c (X=NH) > 3a (X=O) > 3b (X=S). LogP values of three compounds were found to be X=O: 4.03, X=S: 4.63 and X=NH: 3.79. So, the partition coefficient is in this order: X=S: 4.63 > X=O: 4.03 > X=NH: 3.79. Partition coefficient of X=S is 4.63 which is greater than X=O (4.03) and X=NH (3.79). Electronegativity of S is 2.58 which is in between O=3.44 and NH=3.04. Electronegative atoms O and S both have two lone pair of electrons but electronegativity for O: 3.44 > N: 3.04 > S: 2.58. The electronegativity of N is 3.04 so the NH compound (guanidine) showed maximum CNS depression, electronegativity of O is 3.44 so the O compound (urea) showed medium CNS depression and the electronegativity of S is 2.58 so the S compound (thiourea) showed minimum CNS depression. The log P values of NH compound (guanidine) is 3.79 which is minimum but showed maximum CNS depression, log P value of O compound (urea) is 4.03 which showed medium CNS depression and log P value of S compound (thiourea) is 4.63 which showed minimum CNS depression. Oxygen and Sulfur both have two lone pairs of electrons so the CNS depression has been found lesser than NH group which has one lone pair of electrons and the potency of CNS depression is due to the difference in electronegativity: O: 3.44, S: 2.58 and NH: 3.79.
Schiff base, Mannich base, cut off, sleeping time
