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

Biol Pharm Bull. 2004 Oct;27(10):1683-7. doi: 10.1248/bpb.27.1683.

Abstract

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.

MeSH terms

  • Animals
  • Anticonvulsants / chemical synthesis*
  • Anticonvulsants / pharmacology*
  • Anticonvulsants / toxicity
  • Antihypertensive Agents / chemical synthesis*
  • Antihypertensive Agents / pharmacology*
  • Antihypertensive Agents / toxicity
  • Magnetic Resonance Spectroscopy
  • Mice
  • Quinolines / chemical synthesis*
  • Quinolines / pharmacology*
  • Quinolines / toxicity
  • Rats
  • Rats, Wistar
  • Spectrophotometry, Infrared
  • Structure-Activity Relationship

Substances

  • Anticonvulsants
  • Antihypertensive Agents
  • Quinolines