Synthesis and analgesic action of N-(substituted-ethyl)pyrrole-3,4-dicarboximides.
We prepared a series of new N-[2-(4-substitutedpiperazin-1-yl)ethyl]-1-(n-butyl or phenyl)-2,5-dimethyl-3,4-pyrroledicarboximides 3 and the related products 4 and 5, nine representatives of which were evaluated as potential analgesic agents in an animal model (mice). The new pyrroledicarboximides were not toxic (LD50 > or = 1466 mg/kg) and eight of them displayed analgesic activity approximately 1.5-5 times superior to that of ASA in the writhing test. However, the compounds were found to be unstable in methanol solution and in dilute bases (methanol/NaOMe). The S-A relationship is discussed.
Malinka
W
W
Department of Chemistry of Drugs, Wrocław Medical University, ul. Tamka 1, 50-137 Wrocław, Poland. malinka@bf.uni.wroc.pl
Kaczmarz
M
M
Redzicka
A
A
Filipek
B
B
Sapa
J
J
D000698:Analgesia; D000700:Analgesics / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D013329:Structure-Activity Relationship
D000700:Analgesics; D011758:Pyrroles