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 ≥ 1466 mg/kg) and eight of them displayed analgesic activity ~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.