Synthesis of Mannich Bases of Arylidenepyridazinones as Analgesic Agents

Abstract 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 ≤ ED 50 ≤ 43.0 mg/kg, orally; ED 50 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.