ChemInform Abstract: UNEXPECTED ANTIINFLAMMATORY ACTIVITY OF STRUCTURALLY RIGID COMPOUNDS DERIVED FROM ANTIHYPERTENSIVE 6‐ARYLPYRIDAZINONES. III. SYNTHESIS AND ACTIVITY OF 7‐FLUORO AND 5‐OXO‐5H‐INDENO(1,2‐C)PYRIDAZINES
Abstract:Bei der Reaktion von p‐Fluorbenzoylpropionsäure (I) mit Formaldehyd und Alkali erhält man neben der Fluorbenzoylbutensäure (II) das Fluorbenzoyl‐furanon (III), welches zum Fluor‐indanon (IV) cyclisiert werden kann.
“…Benzylation of 3-hydroxy-5 H -indeno[1,2- c ]pyridazin-5-one, synthesized according to the method reported by Cignarella et al., was achieved upon reaction with benzyl bromide in refluxing EtOH in the presence of K 2 CO 3 (Scheme ). 2 …”
Section: Resultsmentioning
confidence: 99%
“…3-(Benzyloxy)-5 H -indeno[1,2- c ]pyridazin-5-one (1h). To a stirred solution of 3-hydroxy-5 H -indeno[1,2- c ]pyridazin-5-one (0.396 g, 2 mmol), prepared according a reported procedure, in 20 mL of EtOH, were added K 2 CO 3 (0.276 g, 2 mmol) and excess of benzyl bromide (1.03 g, 6 mmol). The reaction mixture was refluxed for 30 min and, after cooling to rt, filtered through a Celite pad.…”
A number of condensed azines, mostly belonging to the families of indeno-fused pyridazines (1), pyrimidines (2, 3), and 1,2,4-triazines (4, 5), were synthesized and evaluated in vitro as monoamine oxidase (MAO) A and B inhibitors. Most of them showed higher inhibition potency toward MAO-B, the most effective one being 3-(3-nitrophenyl)-9H-indeno[1,2-e] [1,2,4]triazin-9-one (4c), which displayed an IC50 value of 80 nM and proved to be 10-fold more potent than its [2,1-e] fusion isomer 5. Replacing the 3-phenyl group of the known indeno[1,2-c]pyridazin-5-one MAO-B inhibitors with a flexible phenoxymethyl group enhanced the inhibitory potency. The inhibition data highlighted the importance of the aza-heterocyclic scaffold in affecting the MAO isoform selectivity. The 3-phenyl derivatives with type 1, 4, and 5 scaffolds were inhibitors of MAO-B with little or no MAO-A effect, whereas 2- or 3-phenyl derivatives of type 2 and 3 pyrimidine-containing fusion isomers inhibited both isoenzymes with a structure-dependent preference toward MAO-A.
“…Benzylation of 3-hydroxy-5 H -indeno[1,2- c ]pyridazin-5-one, synthesized according to the method reported by Cignarella et al., was achieved upon reaction with benzyl bromide in refluxing EtOH in the presence of K 2 CO 3 (Scheme ). 2 …”
Section: Resultsmentioning
confidence: 99%
“…3-(Benzyloxy)-5 H -indeno[1,2- c ]pyridazin-5-one (1h). To a stirred solution of 3-hydroxy-5 H -indeno[1,2- c ]pyridazin-5-one (0.396 g, 2 mmol), prepared according a reported procedure, in 20 mL of EtOH, were added K 2 CO 3 (0.276 g, 2 mmol) and excess of benzyl bromide (1.03 g, 6 mmol). The reaction mixture was refluxed for 30 min and, after cooling to rt, filtered through a Celite pad.…”
A number of condensed azines, mostly belonging to the families of indeno-fused pyridazines (1), pyrimidines (2, 3), and 1,2,4-triazines (4, 5), were synthesized and evaluated in vitro as monoamine oxidase (MAO) A and B inhibitors. Most of them showed higher inhibition potency toward MAO-B, the most effective one being 3-(3-nitrophenyl)-9H-indeno[1,2-e] [1,2,4]triazin-9-one (4c), which displayed an IC50 value of 80 nM and proved to be 10-fold more potent than its [2,1-e] fusion isomer 5. Replacing the 3-phenyl group of the known indeno[1,2-c]pyridazin-5-one MAO-B inhibitors with a flexible phenoxymethyl group enhanced the inhibitory potency. The inhibition data highlighted the importance of the aza-heterocyclic scaffold in affecting the MAO isoform selectivity. The 3-phenyl derivatives with type 1, 4, and 5 scaffolds were inhibitors of MAO-B with little or no MAO-A effect, whereas 2- or 3-phenyl derivatives of type 2 and 3 pyrimidine-containing fusion isomers inhibited both isoenzymes with a structure-dependent preference toward MAO-A.
“…The pyridazinone derivatives exhibit antihypertensive activity by virtue of their vasorelaxant property. In 1980s, 6-arylpyridazinones were synthesized, and the compounds such as 7-fluoro and 5-keto-5H-indeno(1,2-c)pyridazines (8) (Cignarella et al, 1982) were found to be antihypertensive. Around the same time, many other pyridazinone derivatives were synthesized and evaluated for various pharmacodynamic properties.…”
In the last few years, the pyridazine derivatives have been found to exhibit a wide range of pharmacological activities. A large number of research articles and patents described them, and several drugs based on its nucleus have come into light. Pyridazinone, a derivative of pyridazine, was initially exploited in search of cardiovascular drugs and for its use in agrochemicals, but later on this nucleus was found to be associated with plethora of activities. In this article, we have reviewed the influence of structural changes on the pharmacodynamic profile of the pyridazinone moiety.
“…5 The 3-(2H)-pyridazinone nucleus is found in drugs that act on the cardiovascular system [6][7][8][9][10] or inflammatory system (Figure 1). [11][12][13][14][15][16][17][18][19] Compounds possessing this nucleus have been shown to exhibit a diverse range of pharmaceutical properties such as anticancer, 20 nephrotropic, [21][22][23][24] analgesic, 12,13 antidepressant, 11 hypotensive, 8,25,26 antianemic, 27 antibacterial, 28 antiaggregative 29 and antifungal activities. 30 Pyridazine derivatives are also well-known compounds in agrochemical research.…”
This Account focuses on the palladium-catalysed crosscoupling reactions of pyridazines. The pyridazine moiety is of significant importance in the pharmaceutical as well as the agrochemical field. Synthetic transformations on this moiety, to yield several diverse analogues for a wide array of applications, have received a considerable boost with the advent of palladium-catalysed crosscoupling reactions. These reactions facilitate the direct introduction of suitable groups on the pyridazine nucleus via carbon-carbon or carbon-heteroatom bond formations. This Account presents a brief account of the inherent advantages of palladium chemistry on this moiety followed by seminal work and subsequent developments on this topic. 4Conclusion
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