Pharmacological evaluation of some new 2-substituted pyridine derivatives

Abstract

In the present study, a series of 2-substituted-pyridines were synthesized and characterized by IR, 1H-NMR and Elemental Analysis. The compounds were assayed against seizures induced by maximal electro shock (MES) and pentylenetetrazole (scMet). Neurologic deficit was evaluated by the rotarod test. The decrease in the elevated motor activity by introceptive chemical stimuli (amphetamine antagonistic activity) was studied at the dose level of 25 and 50 mg/kg, antihistaminic and cardiac activity were also studied. All the compounds exhibited significant anticonvulsant activity. Compounds 2-(2′-piperazino-ethanoxy)pyridine, 2-(3′-morpholino-2′- hydroxypropyloxy)pyridine, 2-(3′-piperidino-2′-hydroxypropyloxy) pyridine and 2-(3′-piperazino-2′-hydroxypropyloxy)pyridine were most active of the series against MES-induced seizures. Compounds 2-(2′-piperazino-ethanoxy)pyridine, 2-(2′-phenylamino-ethanoxy) pyridine, 2-(3′-imidazolo-2′-hydroxypropyloxy)pyridine, 2-(3′-methylamino-2′-hydroxypropyloxy)pyridine and 2-(3′-piperidino-2′-hydroxypropyloxy)pyridine exhibited significant decrease in the elevated motor activity at the dose of 50 mg/kg. Remarkable sympathetic blocking activity was observed with 2-(3′-piperazino-2′- hydroxypropyloxy)pyridine, 2-(3′-piperidino-2′-hydroxypropyloxy) pyridine and 2-(3′-imidazolo-2′-hydroxypropyloxy)pyridine only. Compounds 2-(2′-morpholino-ethanoxy)pyridine, 2-(2′-piperidino- ethanoxy)pyridine, 2-(2′-piperazino-ethanoxy)pyridine, 2-(2′-imidazolo-ethanoxy)pyridine, 2-(2′-diphenylamino-ethanoxy) pyridine, 2-(2′-diethanolamino-ethanoxy)pyridine, 2-(2′-phenylamino- ethanoxy)pyridine and 2-(2′-(4″-hydroxy)phenylamino-ethanoxy) pyridine exhibited significant blocking of histamine induced contraction on guinea pig ileum. © 2003 Pharmaceutical Society of Japan.