Synthesis, anticonvulsant and antihypertensive activities of 8-substituted quinoline derivatives.

A series of 8-substituted quinolines were synthesized and tested against seizures induced by maximal electro shock (MES), pentylenetetrazole (scMet) and antihypertensive activities. Neurologic deficit was evaluated by the rotarod test. Among the newly synthesized derivatives, several compounds with a 2-hydroxypropyloxyquinoline moiety displayed excellent anticonvulsant and antihypertensive activities. Compound 20 (8-(3'-(4''-phenylpiperazino)-2'-hydroxypropyloxy)quinoline) was potent in both series as an anticonvulsive agent. 13 (8-(3'-piperazino)-2'-hydroxypropyloxyquinoline) and 14 (8-(3'-imidazolo)-2'-hydroxypropyloxyquinoline) showed very good anticonvulsant activities in the propanol series of compound, whereas in the ethane series, 1 (8-(2'-piperazino-ethanoxy)quinoline) and 2 (8-(2'-imidazolo-ethanoxy)quinoline) were the most active as anticonvulsive agents. Compounds 20 (8-(3'-(4''-phenylpiperazino)-2'-hydroxypropyloxy)quinoline), 13 (8-(3'-piperazino)-2'-hydroxypropyloxyquinoline) and 19 (8-(3'-(4''-ethylpiperazino)-2'-hydroxypropyloxy)quinoline) have shown excellent antihypertensive activity. They have significantly antagonized the pressor response elicited by adrenaline. These pharmacological results suggest that their anticonvulsant and antihypertensive effects may be correlated to the presence of beta-blocking properties, and that those properties depend on the presence of aryloxypropanolamine.

Synthesis and anticonvulsant activity of novel 1-substituted-1,2-dihydro-pyridazine-3,6-diones.

The synthesis and pharmacological evaluation of novel 1-substituted-1,2-dihydro-pyridazine-3,6-diones (4a--l, 5a--j) as potential anticonvulsant agents are described. The compounds were tested in vivo for the anticonvulsant activity. The compound which have maximum protection against MES induced seizures is 1-[3-(2-aminophenylamino)-2-hydroxypropyl)-1,2-dihydro-pyridazine-3,6-dione 4h (ED(50)=44.7 mg x kg(-1) i.p.) 1-[2-hydroxy-3-piperazin1-yl-propyl)-1,2-dihydro-pyridazine-3,6-dione 4c (ED(50)=72 mg x kg(-1) i.p.) and 1-[2-hydroxy-3-imidazol-1-yl-propyl)-1,2-dihydro-pyridazine-3,6-dione 4d (ED(50)=79 mg x kg(-1) i.p.) were also found to have maximum protection against MES induced seizures. Whereas all these compounds failed to protect the animals from subcutaneous pentylenetetrazole (Metrozol) seizure threshold test (sc-Met).

Pharmacological evaluation of some new 6-amino/methyl pyridine derivatives.

In the present study, a series of 2-substituted-pyridines were synthesized and characterized by IR, (1)H-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-hydroxy-3-piperazinopropylamino)-6-aminopyridine, 2-[2-hydroxy-3-(1-imidazolyl)propylamino]-6-aminopyridine, 2-[2-(1-imidazolyl)ethylamino]-6-methylpyridine and 2-[2-(methylamino)ethylamino]-6-methylpyridine were most active of the series against MES-induced seizures. Compounds 2-[2-(phenylamino)ethylamino]-6-aminopyridine, 2-[2-[bis(2-hydroxyethyl)amino]ethylamino]-6-aminopyridine, 2-[2-(diethylamino)ethylamino]-6-methylpyridine and 2-[2-hydroxy-3-(1-imidazolyl)propylamino]-6-methylpyridine exhibited significant decrease in the elevated motor activity at the dose of 50 mg/kg. Remarkable sympathetic blocking activity was observed with 2-(2-hydroxy-3-piperazinopropylamino)-6-aminopyridine, 2-(2-hydroxy-3-morpholinopropylamino)-6-methylpyridine and 2-(2-hydroxy-3-piperazinopropylamino)-6-methylpyridine only. Compounds 2-[2-(diethylamino)ethylamino]-6-aminopyridine, 2-[2-[bis(2-hydroxyethyl)amino]ethylamino]-6-aminopyridine, and 2-[2-(diethylamino)ethylamino]-6-methylpyridine exhibited significant blocking of histamine induced contraction on guinea pig ileum.

Pharmacological evaluation of some new 2-substituted pyridine derivatives.

In the present study, a series of 2-substituted-pyridines were synthesized and characterized by IR, (1)H-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.