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Synthesis, Acute Toxicity, and Analgesic Activity of New Derivatives of Pyrrole
Author(s) -
Danchev Nikolai,
Bijev Atanas,
Yaneva Diana,
Vladimirova Stanislava,
Nikolova Irina
Publication year - 2006
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.200600116
Subject(s) - analgesic , toxicity , chemistry , pharmacology , pyrrole , acute toxicity , biological activity , medicine , biochemistry , organic chemistry , in vitro
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‐dependant 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)‐1 H ‐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 .