An Efficient Synthesis and Reactions of Novel Indol-ylpyridazinone Derivatives with Expected Biological Activity

Abstract

Reaction of 4-anthracen-9-yl-4-oxo-but-2-enoic acid (1) with indole gave the corresponding butanoic acid 2. Cyclocondensation of 2 with hydrazine hydrate, phenyl hydrazine, semicarbazide and thiosemicarbazide gave the pyridazinone derivatives 3a-d. Reaction of 3a with POCl 3 for 30 min gave the chloropyridazine derivative 4a, which was used to prepare the corresponding carbohydrate hydrazone derivatives 5a-d. Reaction of chloropyridazine 4a with some aliphatic or aromatic amines and anthranilic acid gave 6a-f and 7, respectively. When the reaction of the pyridazinone derivative 3a with POCl 3 was carried out for 3 hr an unexpected product 4b was obtained. The structure of 4b was confirmed by its reaction with hydrazine hydrate to give hydrazopyridazine derivative 9, which reacted in turn with acetyl acetone to afford 10. Reaction of 4b with methylamine gave 11, which reacted with methyl iodide to give the trimethylammonium iodide derivative 12. The pyridazinone 3a also reacted with benzene-or 4-toluenesulphonyl chloride to give 13a-b and with aliphatic or aromatic aldehydes to give 14a-g. All proposed structures were supported by IR, 1 H-NMR, 13 C-NMR, and MS spectroscopic data. Some of the new products showed antibacterial activity.

Methyl 4-{[6-(4-bromophenyl)-3-oxo-2,3,4,5-tetrahydropyridazin-4-yl]methyl}benzoate

“…Heterocyclic compounds containing 3-(2H)-pyridazinone moiety in their structures have attracted a great deal of attention due to their wide spectrum of biological activity such as antimicrobial (Sayed et al, 2002;Katrusiak & Baloniak, 1994), antiinflammatory (Dogruer et al, 2003;Pieretti et al, 2006), antifeedant (Cao et al, 2003), herbicidal (Piaz et al, 1994;Xu et al, 2008), antiplatelet Coelho et al, 2007), anticancer (Malinka et al, 2003), antihypertensive (Wexler et al, 1996;Barbaro et al, 2001), antinociceptive agent Vergelli et al, 2007) and other biological and pharmacological properties (Abudshait, 2007). In our study toward the synthesis of dihydropyridazinones as potential candidates for antihypertensive activity the structure of methyl 4-[6-(4-bromophenyl)-3-oxo-2,3,4,5-dihydropyridazin-4-ylmethyl]benzoate has been determined.…”

“…For the biological activity of heterocyclic compounds containing the 3(2H)-pyridazinone group, see: Sayed et al (2002); Katrusiak & Baloniak (1994); Dogruer et al (2003); Pieretti et al (2006); Cao et al (2003); Piaz et al (1994); Xu et al (2008); Giovannoni et al (2007); Coelho et al (2007); Malinka et al (2003); Wexler et al (1996); Barbaro et al, (2001); Vergelli et al (2007); Abudshait (2007). For related structures, see: Zhang et al (2006); Zhou & Zhou (2007).…”

Synthesis and Antitubercular Activity of Pyridazinone Derivatives

“…Preparation of 3-(4-Chloro/methyl benzoyl)propionic acid (1,2). The compounds, 1 and 2, were synthesized according to the reported method [14].…”

“…Differently substituted pyridazinones have been found to have potential antibacterial, antifungal and antiviral including anti-HIV activities [1][2][3][4]. Various 3-(2H)-pyridazinone derivatives have shown anticancer [4], analgesic & anti-inflammatory [4][5][6], anticonvulsant [7], cardiotonic & hypotensive [8,9] and antiulcer activities [10].…”

Biological Potential and Chemical Properties of Pyridine and Piperidine Fused Pyridazine Compounds: Pyridopyridazine a Versatile Nucleus

“…Pyridazines are widely recognized as versatile scaffolds with a diverse set of biological activities [12][13][14][15] . Among pyridazine derivatives, pyridazinones is an important class of compounds mainly due to their diverse biological activities like analgesic, anti-inflammatory, antibacterial, herbicidal, antifungal, antituberculotic, anti-AIDs, antitumour, antihypertensive, anticonvulsant, anticancer, and antiviral activities [16][17][18][19][20] . In pyridazinones the amine group (NH) is suitably placed with the carbonyl group and most of the pyridazinones exhibit tautomerism.…”