الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
The Present work aimed to synthesis some novel quinazolinone and fused quinazoline derivatives from the reaction of 3, 1-benzoxazine-3(4H)-one 65 with different nitrogen nucleophiles.
The treatment of 65 with methyl glycinate hydrochloride in dry pyridine gave the open chain adduct of methyl acetate derivative 66, while heating benzoxazine-one 65 with hydroxyl amine hydrochloride in dry ethanol and presence of a catalytic amount of freshly fused sodium acetate afforded the cyclic N-hydroxy quinazolinone derivative 67.
Heating of benzoxazine-one 65 with cyanoacetohydrazide in ethanol and in the presence of few drops of glacial acetic acid yielded the fused pyrazolo-quinazoline derivative N-acetyl-N-(1-(1-cyano-2-oxo-2,3-dihydropyrazolo[1,5-c]quinazolin-5-yl)-2-(naphthalen-1-yl)vinyl)benzamide(68). Similar treatment of 65 with thiocarbohydrazide afforded the fused 1, 2, 4, 5-tetrazino-quinazoline derivative 69 in a good yield.
Refluxing of benzoxazine-one 65 with sodium azide in dry pyridine gave a mixture of 1-(naphthalen-1-yl)-3-oxo-3-(2-oxo-2,3-dihydro-1Hbenzo[d]imidazol-1-yl)prop-1-en-2-yl)acetamide (70) (major) and 2-(5-(1-acetamido-2-(naphthalen-1-yl)vinyl)-1H-tetrazol-1-yl)benzoic acid (71) (minor).
The treatment of 65 with hydrazine hydrate in refluxing ethanol afforded the open chain adduct 3-((2-(hydrazinecarbonyl)phenyl)amino)-1-(naphthalen-1-yl)-3-oxoprop-1-en-2-yl)benzamide(72). While, on carrying out the same reaction in an excess of hydrazine hydrate we obtain the cyclized N-amino quinazolinone derivative 73.
Fusion of 65 with ammonium acetate or refluxing it in formamide afforded the 4-oxo-3, 4-dihydroquinazolinone derivatives 74.
Part (2)
This part aimed to utilize N-amino quinazolinone 73 and quinazolinone 74 in the synthesis of N-3 functionalized quinazolinone derivatives with anticipated biological activity.
Refluxing an equimolar amount of 73 with aromatic aldehydes namely vanillin, p-anisaldehyde, and 2-chloroquinoline-3-carbaldehyde in refluxing ethanol and glacial acetic acid afforded the hydrazone derivatives 75-77, respectively in good yields.
Reaction of N-amino quinazolinone derivative 73 with phenyl isothiocyanate in dry benzene gave 2-(naphthalen-1-yl)-1-(4-oxo-3-(3-phenylthioureido)-3, 4-dihydroquinaz- olin-2-yl)vinyl)benzamide (78). Fusion of compound 78 on sand bath above its melting point furnished the fused triazino-quinazolinone derivative 79.
Refluxing an equimolar amounts of quinazolinone 74 with ethyl chloroacetate in dimethyl formamide and traces of potassium hydroxide gave ethyl 2-(2-(1-benzamido-2-(naphthalen-1-yl)vinyl)-4-oxoquinazolin-3(4H)-yl)acetate (81).
Heating of ethyl acetate derivative 81 with hydrazine hydrate in refluxing ethanol afforded the carbohydrazide derivative 82. The later compound underwent nucleophilic addition reaction with different carbon electrophiles namely acetic anhydride, acetyl acetone, ethyl cyanoacetate, benzoyl chloride, and carbon disulfide afforded new oxadiazole and pyrazole derivatives 83-87, respectively.
Structural assignment of all new synthesized compounds was based on their infrared, mass spectra and nuclear magnetic resonance. Also, the biological activity of the newly synthesized compounds was screened against different bacteria and fungi strains, the results revealed that most of the synthesized compounds showed medium and / or high antimicrobial activity compared to the standard ciprofloxacin and clotrimazole drugs. Molecular docking studies of the most potent synthesized compounds were performed to investigate their antimicrobial inhibition activity and studying their potential binding modes within the active site of different macromolecules including bacterial and fungus species. The results revealed that the tested compounds embedded well within the target bacterial and fugus enzymes with energy scores in between 5.20-8.76, and 6.32-10.35 kcal/mol, respectively. That was in accordance with the experimental results.