الفهرس 
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Abstract
Amino acids can be defined as simple organic compounds containing both a carboxyl (—COOH) group and an amino (—NH₂) group. Because of their role as precursors in many biological processes, their structures are common to the human body’s various receptors. Here, we aimed to incorporate amino acids in newly designed compounds as a strategy to improve targets’ bioavailability and hence biological activity.
A series of N-(4-substitutedphenyl)-4-(1-methyl (or 1,2 dimethyl) -4-oxo-1,2-dihydroquinazolin-3(4H)-yl)alkanamide (VIIa-j) and 4-chloro-N’-((1-methyl or (1,2 dimethyl)-4-oxo-1,2-dihydroquinazolin-3(4H)yl)alkaloyl) benzohydrazide (VIIIa-f) have been designed based on the previously reported essential structural features for anticonvulsant activity. The new quinazolinone derivatives were evaluated for their anticonvulsant activity according to anticonvulsant drug development (ADD) program protocol. All the sixteen new quinazolinones exhibited good anticonvulsant activity especially VIIf, VIIb, VIIc that showed superior anticonvulsant activities in comparison to the reference drug with ED50 28.90, 47.38, 56.40 mg/kg respectively.
Novel quinazolin-4(3H)-ones were synthesized using the following routes:
1- Methylation of the amino group in Anthranilic acid (I) using equivalent amount of dimethyl sulphate that added to a stirred solution of (I) in water containing half equivalent of Na2CO3, that afforded 2-(methylamino)benzoic acid (N- methyl anthranilic acid) (II).
2- Refluxing the 2-(methylamino)benzoic acid (II) with neat ethyl chloroformate for 4 h, that yielded 1-methyl-1H-benzo[d] [1,3]oxazine-2,4-dione (N- methyl isatoic anhydride) (III).3- Reacting N- methyl isatoic anhydride (III) with equivalent amount of the appropriate amino acid in presence of equivalent amount of triethylamine in water solvent at 40-50ᵒC for 4 h, then the neutralized with 1N HCl to afford (2-(methylamino)benzamido) carboxylic acids (IVa-c).
4- Refluxing (2-(methylamino)benzamido) carboxylic acids (IVa-c) with appropriate aldehyde in 40% ethanol/water solvent that afforded (1-methyl (or1,2-dimethyl) -4-oxo-1,2-dihydroquinazolin-3(4H)-yl) carboxylic acid (Va-f).
5- Reacting (1-methyl (or 1,2-dimethyl)-4-oxo-1,2-dihydroquinazolin-3(4H)-yl) carboxylic acid (Va-f) with 3 equivalent 1H benzotriazole and 1.2 equivalent thionyl chloride in dry methylene chloride at room temperature for 4.5 h, that yielded 3-(1H-benzo[d][1,2,3]triazol-1-yl)-3-oxoalkyl)-1-methyl(or1,2-dimethyl)-2,3 dihydroquinazolin-4(1H)-one (VIa-f).
6- Finally, reacting 3-(1H-benzo[d][1,2,3]triazol-1-yl)-3-oxoalkyl)-1-methyl(or1,2-dimethyl)-2,3 dihydroquinazolin-4(1H)-one (VIa-f) with either equivalent amount 4- substituted anilines that afforded N-(4-substitutedphenyl)-4-(1-methyl (or 1,2 dimethyl) -4-oxo-1,2-dihydroquinazolin-3(4H)-yl) alkanamide (VIIa-j), or with equivalent amount of p-chlorobenzoic acid hydrazide that afforded 4-chloro-N’-((1-methyl or (1,2 dimethyl)-4-oxo-1,2-dihydroquinazolin-3(4H)-yl)alkaloyl)benzohydrazide (VIIIa-f) using THF as solvent and 1.5 equivalent of triethylamine.