Synthesis and biological evaluation of new series of phthalazinone, pyridazinone, oxadiazole, pyrazolone scaffolds based on coumarin-3-carbohydrazide

Abstract

A new series of phthalazinone, pyridazinone, oxadiazole, pyrazolone scaffolds based on coumarin-3-carbohydrazide was efficiently synthesized. Reaction of hydrazine hydrate with 2-oxo-2H-chromene carboxylate (1) produced the key compound coumarin-3-carbohydrazide (2), which used for synthesizing Schiff ' s base derivatives (3a-d).The hydrazide (2) was used for efficient synthesis of different scaffolds such as dihydrophthalazine-1,4-Dione (4a, 4b), pyridazinone derivatives (5) and (6) via treatment with phthalic anhydride and/or tetrabromo phthalic anhydride, maleic anhydride and succinic anhydride, respectively. Moreover, Reaction of benzoic acid and/or acetic acid with coumarin-3carbohydrazide (2) in phosphorous oxychloride produced the oxadiazole derivatives (8a, b).Pyrazolone and pyrazolidinone scaffolds (9-12) were obtained in good yields upon reaction of the hydrazide derivative (2) with numerous active methylene compounds such as acetylacetone, ethyl cyanoacetate, ethyl acetoacetate, and diethyl malonate.Evaluation of antimicrobial activity of some of the synthesized compounds towards the selected bacteria and fungi strains in comparison with Gentamicin and ketoconazole as reference drugs revealed that compounds 3d, 6, 8a, 8b, 11, 12 and 14 exhibited promising activity in comparison to the tested standard.The products structures were assigned and confirmed via their elemental analyses as well as spectral data (IR, MS and

Phthalic anhydride (PA): a valuable substrate in organic transformations

“…Aly's group in 2022 interpreted that the coumarin hydrazide ( 118 ) treated with PA ( 1 ) to furnish 2-(2-oxo-2 H -chromene-3-carbonyl)-2,3-dihydrophthalazine-1,4-dione ( 119 ) by 76% yield (Scheme 42). 153…”

“…152 Aly's group in 2022 interpreted that the coumarin hydrazide (118) treated with PA (1) to furnish 2-(2-oxo-2H-chromene-3carbonyl)-2,3-dihydrophthalazine-1,4-dione (119) by 76% yield (Scheme 42). 153 In 2019, 2-(6-iodo-4-oxo-2-undecylquinazolin-3(4H)-yl)acetohydrazide (120) reacted with PA (1) to produce 2-undecyl-4(3H)quinazolinone (121), which was obtained by either conventional method or by the microwave-assisted technique. The adduct was tested in vitro against a panel of three human tumor cell lines, namely, Hepatocellular Carcinoma (liver) HepG2, colon cancer HCT-116, and mammary gland breast MCF-7, which demonstrated satisfactory activity (Scheme 43).…”