Synthesis of Mannich bases of arylidenepyridazinones as analgesic agents

Article abstract of DOI:10.1002/jps.2600811108

A series of 5-arylidenepyridazin-3-ones substituted in the 2-position by an arylpiperazinoalkyl moiety (2-16) was synthesized and evaluated for analgesic activity. In the phenylbenzoquinone-induced writhing test, Mannich bases 2-14 were the most active compounds (6.1 ≤ ED₅₀ ≤ 43.0 mg/kg, orally; ED₅₀ is the half-maximal effective dose). Pyridazinones 8 and 9, with a 3-chlorophenylpiperazinomethyl substituent, also exhibited significant anti-inflammatory and antipyretic effects. The activities in the phenylbenzoquinone-induced writhing test were subjected to a Hansch analysis, and a significant correlation with lipophilicity and Hammett's constants was obtained.