Hany M. Hassanin

Studies on the chemical behavior of 3-(nitroacetyl)-1-ethyl-4-hydroxyquinolin-2(1H)-one towards some electrophilic and nucleophilic reagents

A variety of heterocyclic systems linked to 1-ethylquinolin-2(1H)-one was prepared from reaction of 3-(nitroacetyl)-1-ethyl-4-hydroxyquinolin-2(1H)-one with some electrophilic and nucleophilic reagents. Besides its cyclization to 5-ethyl-2-(hydroxyimino)-2,3,4,5-tetrahydrofuro[3,2-c]quinoline-3,4-dione, the 3-(nitroacetyl)-1-ethyl-4-hydroxyquinolin-2(1H)-one has been brominated, chlorinated, formylated, acetylated, and condensed with chromone-3-carbonitrile and 2-amino-3-formylchromone. Some new pyrazolo[4,3-c]quinoline, pyrimido[5,4-c]quinoline and quinolino[4,3-b][1,5]benzodiazepine derivatives were also synthesized.

Synthesis, Characterization, and Antimicrobial Evaluation of Some Novel 4-Hydroxyquinolin-2(1H)-ones

Abstract Vilsmeier–Haack formylation of 3-acetyl-1-methyl-4-hydroxyquinolin-2(1H)-one (2) produced the novel 6-methyl-4,5-dioxo-5,6-dihydro-4H-pyrano[3,2-c]quinoline-3-carboxaldehyde (3). Reactions of carboxaldehyde 3 with a diversity of nucleophilic reagents were studied and a variety of products were obtained via ring-opening, ring-closing (RORC) sequence. Also, some novel heteroannulated pyrano[3,2-c]quinolines were prepared. Structures of the new synthesized products were deduced on the basis of their analytical and spectral data. GRAPHICAL ABSTRACT

Substituted quinolinones 27.* Regioselective synthesis of pyrazolo-, oxazolo-, and triazepinoquinoline derivatives

Reactivity of 3-acetyl-4-(methylsulfanyl)quinolin-2(1H)-one towards 1,2- and/or 1,4-diazanucleophiles has been studied under different reaction conditions. Condensation of 3-acetyl-4-(methylsulfanyl)quinolin-2(1H)-one with hydrazine, phenylhydrazine, hydroxylamine hydrochloride, semicarbazide, and thiosemicarbazide was carried out in different media. The structure of the reaction products was dependent not only on the reagent used, but also on the solvent and reaction temperature. Accordingly, the reaction regioselectively produced in good yields pyrazolo[3,4-b]quinoline, pyrazolo[4,3-c]quinoline, oxazolo[5,4-b]quinoline, oxazolo[4,5-c]quinoline, isoxazolo-[4,5-c]quinoline, [1, 2, 4]triazepino[5,6-b]quinoline, and [1,2,4]triazepino[6,5-c]quinoline derivatives in addition to open-chain condensates which, too, were transformed to the respective cyclic products. The structures of new products were established on basis of their analytical and spectral data.

Substituted quinolinones. Part 23. Synthesis of 6-ethyl-4,5-dioxo- 5,6-dihydro-4H-pyrano(3,2-c)quinoline-3-carboxaldehyde and its chemical behavior towards hydroxylamine hydrochloride

The synthesis of novel 6-ethyl-4,5-dioxo-5,6-dihydro-4H-pyrano[3,2-c]quinoline-3-carboxaldehyde is described via Vilsmeier-Haack reaction of 3-acetyl-1-ethyl-4-hydroxyquinolin2(1H)-one. The reaction of titled aldehyde with hydroxylamine hydrochloride, under different conditions, revealed its distinctive chemical behavior and a variety of products were obtained. This study revealed existence of ring-opening ring-closure (RORC) on treatment with hydroxylamine hydrochloride in both acetic acid and/or ethanolic potassium hydroxide. The structure of the new products was deduced on basis of their analytical and spectral data.

Synthesis and molecular docking studies of some novel Schiff bases incorporating 6-butylquinolinedione moiety as potential topoisomerase IIβ inhibitors

A series of novel pyranoquinolinone-based Schiffs bases were designed and synthesized. They were evaluated for topoisomerase IIβ (TOP2B) inhibitory activity, and cytotoxicity against breast cancer cell line (MCF-7) for the development of novel anticancer agents. A molecular docking study was employed to investigate their binding and functional properties as TOP2B inhibitors, using the Discovery Studio 2.5 software, where they showed very interesting ability to intercalate the DNA–topoisomerase complex. Compounds 2a, 2c and 2f showed high docking score values (82.36% −29.98 kcal mol−1 for compound 2a, 78.18% −26.98 kcal mol−1 for compound 2c and 78.65, −28.11 kcal mol−1 for compound 2f) and revealed the highest enzyme inhibition activity. The best hit compounds exhibited highly potent TOP2B inhibitors with submicromolar IC50 at 5 µM compared to the reference doxorubicin.

A Convenient and Efficient Method for the Synthesis of a Novel Series of N‑Butyl‑1,4-oxazino[2’,3’:4,5]pyrano[3,2-c]quinolinones

We design and describe here a simple route for the synthesis of a new multi heterocycle fused 1,4-oxazinopyranoquinolinones compatible with many functional groups. This method proceeds through various cyclic condensation reactions of (3-amino or 3-nitropyrano)[3,2-c]quinoline2,5(6H)-dione precursors with different 1,2-bifunctional electrophiles. The synthesized compounds are confirmed by infrared (IR), proton (H) and carbon-13 (C) nuclear magnetic resonance (NMR) spectroscopy and electrospray ionization mass spectrometry (ESI-MS).

Synthesis of new quinolinones from 3-nitropyranoquinolinones

Alkaline hydrolysis of 3-nitropyranoquinolinones (6-alkyl-4-hydroxy-3-nitro-2H-pyrano[3,2-c]quinoline-2,5(6H)-diones) for different reaction times gave five products which were formed by the progressive degradation of the nitropyrano ring. Varying amounts of 3-nitroacetylquinolinones, quinolinones with side-chains of β- and α-ketoacids, quinolinone-3-carboxylic acids and 4-hydroxyquinolinones were isolated. With the aim of preparing new biologically active quinolone derivatives, the products of reaction of the 3-nitropyranoquinolinones with side-chains of β- and α-ketoacids with some nitrogen and carbon nucleophiles were also studied, some giving rise to annulated products.