Abstract:
In the present study, three series of compounds viz., I: 2-{4-[4-(substituted thiazolyl)phenylethyl] piperazin-1-yl}-1,8-naphthyridine-3-carbonitriles (NC : 1-7), II: 4-{4-[2-(4-(2-substituted quinoxalin-3-yl) piperazin-1-yl)ethyl]phenyl} thiazoles (QCC : 1-7; QCMO : 1-7; QCMH : 1-7), IIIa: N-{2-[4-(substituted)piperazin-1-yl]-2-oxo ethyl} acetamide (P : 1-7) and IIIb: N-2-{4-[4-(2-substitutedthiazol-4-yl)piperazin-1-yl]-2-oxo ethyl} acetamide (AG:1-7) were designed in accordance with the strategy promulgated by Ariens targetting Schizophrenia. The designed compounds were synthesized by conventional method and wherever possible, reactions were carried out using microwave irradiation technique under solvent free conditions. The newly synthesized compounds were charaterized by spectral data (IR, 1H NMR and MS) and elemental analysis. The synthesized compounds were evaluated for their 5-HT2A and D2 receptor antagonistic activites in in vivo pharmacological models using Cage Climbing Assay and Quipazine induced head twitches respectively in Swiss albino mice. NCEs were also tested for catalepsy in Swiss albino mice. In series I, the compound NC6 was found to be the most active one with 5-HT2A/ D2 ratio of 1.1143 and an average cataleptic score of zero. In series II, the compound QCMH4 was found to be the most active one with 5-HT2A/ D2 ratio of 1.23 and an average cataleptic score of zero. In series IIIa, the compound P4 was found to be the most active one with 5-HT2A/ D2 ratio of 0.853 and an average cataleptic score of zero. In series IIIb compound AG3 was found to be the most active compound with 5-HT2A/ D2 ratio of 1.128 and an average cataleptic score of zero. Some of the compounds of Series I and series II were also evaluated for their receptor binding affinity at 5-HT2A and D2 receptors using radio ligand binding assays. In series I, NC6 was found to be the most active with Ki of 6.33 and#956;M towards the D2 receptor and 11.2 and#956;M towards the 5-HT2A receptor.
