Synthesis, acute toxicity, and analgesic activity of new derivatives of pyrrole.
Ten pyrrole derivatives (including six new compounds) were synthesized and evaluated as potential platform for analgesic agents' development. Acute intraperitoneal toxicity and analgesic activity studies (acetic acid writhing test) were performed on mice with acetylsalicylic acid used as a reference substance. Products 3c, 3d, 3e, and 3h exhibited a dose-dependent activity demonstrating 1.5 to 2.5-fold better protections than the reference. The most prospective compounds comprised salicylic acid moieties, whose 4-substituted derivatives were related to lower acute toxicity and considerable activity. 4-[3-(Ethoxycarbonyl)-2-methyl-5-(3,4-dimethoxy-phenyl)-1H-pyrrol-1-yl]-2-hydroxy-benzoic acid 3c was pointed out as the most prospective substance due to its lower acute toxicity (378 mg/kg body weight, intraperitoneally) and highest analgesic activity (up to 89.3% protection) in a dose range of 1/10 to 1/40 parts of LD(50).
Danchev
Nikolai
N
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Medicinal University, Sofia, Bulgaria.
Bijev
Atanas
A
Yaneva
Diana
D
Vladimirova
Stanislava
S
Nikolova
Irina
I
D019342:Acetic Acid; D000700:Analgesics / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D007202:Indicators and Reagents; D007928:Lethal Dose 50; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D010147:Pain Measurement / Q000187:drug effects; D011758:Pyrroles / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D013055:Spectrophotometry, Infrared
D000700:Analgesics; D007202:Indicators and Reagents; D011758:Pyrroles; D019342:Acetic Acid