Synthesis and pharmacological screening of a group of piperazine derivatives. Analgesic activity.
Fifteen original piperazine derivatives were synthesized: 11 esters of 1-substituted-4-(3'-phenyl-3'-hydroxypropyl)-piperazines with acetic, propionic, benzoic and phenylacetic acids and 4 symmetrical esters of 1,4-bis-(3'-phenyl-3'-hydroxypropyl)-piperazine with acetic, propionic, benzoic and phenylacetic acids. The compounds were tested with respect to their analgesic and behavioural activity, as well as toxicity. Three nociceptive tests were used: chemical intraperitoneal irritation with acetic acid, thermal contact irritation and thermal radiation irritation. The tests were performed on albino mice breed H. All tested compounds were biologically active and showed analgesic effect. The "therapeutic index" was determined on the basis of the mean effective doses (ED50) and the mean lethal doses (LD50). Most favorable "therapeutical" indices were distinguished in 1,4-bis[3'-phenyl-3'-acetoxypropyl]-piperazine (12), 1-benzhydryl-4[3'-benzyloxypropyl]-piperazine (10) and 1-benzhydryl-4[3'-phenyl-3'-phenylacetyloxypropyl]-piperazine (11).
Nikolova
M
M
Chemical Pharmaceutical Research Institute, Sofia, Bulgaria.
Fajad
K
K
Natova
L
L
D000085:Acetates; D000700:Analgesics / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D005260:Female; D006358:Hot Temperature; D007928:Lethal Dose 50; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010146:Pain / Q000139:chemically induced / Q000517:prevention & control; D010147:Pain Measurement / Q000187:drug effects; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D013055:Spectrophotometry, Infrared
D000085:Acetates; D000700:Analgesics; D010879:Piperazines