Synthesis of Mannich Bases of Arylidenepyridazinones as Analgesic Agents

Studies on Some 3(2H)-Pyridazinone Derivatives with Antinociceptive Activity

“…Additionally, all the compounds that they synthesized exhibited almost no ulcerogenic side effect [16] . Rubat and co-workers stated that N-substituted 5-benzylidene-6-methyl-3-pyridazinone derivatives also show analgesic activity [17,18] .…”

“…Recently it was reported that a considerable number of 3(2H)-pyridazinone derivatives have analgesic activity [6,[13][14][15][16][17][18] . Among these compounds, one of the 3(2H)-pyridazinone derivatives, 4-ethoxy-2-methyl-5-morpholino-3(2H)-pyridazinone (emorfazone) is a well-known analgesic and antiinflammatory agent ( Figure 1) [13,14] .…”

Analgesic and anti-inflammatory activities of several 4-substituted-6-(3'-nitrophenyl)pyridazin-(2H)-3-one derivatives

“…On the other hand, a considerable number of pyridazine-3(2H)one derivatives are endowed with analgesic and antiinflammatory properties (Siddiqui et al, 2004;Dogruer, et al, 2007). Among the various pyridazine compounds, 3-amino-6-methyl-pyridazine-4-thiol (ES-1007) (1) is marketed in Germany (Pyridazine analogue) and 4-ethoxy-2-methyl-5-morpholino-3(2H)-pyridazinone (emorfazone) (1) is being marketed as pentoil and nandron in Japan as an analgesic and anti-inflammatory drug (Rubat, et al, 1992, Pinna et al, 1992Flouzat et al, 1993).…”

[(3-Chlorophenyl)piperazinylpropyl]pyridazinones and Analogues as Potent Antinociceptive Agents

“…It is necessary to take into account that pain is a very complex process in which many different neuromodulators are involved, such as glutamate, acetylcholine, GABA, adrenaline, and so on. 8,[10][11][12] Our experience in the pyridazine field, [13][14][15][16] together with the observation that some pyridazine derivatives such as emorfazone (A, Chart 1), 17 on the market in Japan, and compound B, 18 bearing an alkylpiperazinyl alkyl moiety, show interesting antinociceptive activity not related to effects on prostaglandins or opioid system, led us to design and synthesize a series of pyridazinone derivatives as potential analgesic drugs. In this study we identified compound C 14 as a promising lead, showing good antinociceptive activity in mouse abdominal constrictions model with an ED 50 of 14.9 mg kg -1 , sc (quantal protection of 100% at 100 mg kg -1 ), resulting in 7-fold more potent with respect to emorfazone.…”