Synthesis of Mannich bases of arylidenepyridazinones as analgesic agents.
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 < or = ED50 < or = 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.
Rubat
C
C
Groupe de Recherches en Pharmacochimie, Clermont-Ferrand, France.
Coudert
P
P
Albuisson
E
E
Bastide
J
J
Couquelet
J
J
Tronche
P
P
D000700:Analgesics / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008352:Mannich Bases / Q000138:chemical synthesis* / Q000494:pharmacology; D051379:Mice; D011724:Pyridazines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D008352:Mannich Bases; D011724:Pyridazines