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SYNTHESIS AND BIOCHEMICAL EVALUATION OF NOVEL ANTI-INFLAMMATORY TRIAZOLOQUINAZOLINE AND TRIAZINOQUINAZOLINE DERIVATIVES BEARING SULFA MERAZINE MOIETY

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Author(s): Dr. Mohammed Abdalla Hussein

Journal: International Journal of Pharmaceutical Research and Development
ISSN 0974-9446

Volume: 2;
Issue: 3;
Start page: 1;
Date: 2010;
Original page

Keywords: ulfa merazine | triazoloquinazoline | triazinoquinazolines | antipyretic | anti-inflammatory | LD50 | SGOT | SGPT | ALP | LDH | ? -GT | SOD | GPx | blood GSH and TBARs.

ABSTRACT
This study was carried out to synthesis and biochemical evaluation of some novel of anti-inflammatory triazoloquinazolines and triazinoquinazolines. When compound 2 was reacted with sulfa merazine the thioureido derivative 3 was obtained. By anther method, when sulfa merazine was stirred with carbondisulphide and solution of sodium hydroxide and dimethyl sulphate in dimetylsulphoxide the methyl{4-[(4-methylpyrimido-2-yl)sulfamyl]phenyl} dithiocarbamate 2' was obtained. Stirring of compound 2' with methyl anthranilate in dimethylformamide (DMF) to give compound 3. Refluxing of compound 3 with hydrazine hydrate in ethanol afforded the N-aminoquinazoline derivative 4. When compound 4 was reacted with aromatic aldehydes with aromatic aldehydes in acetic acid containing fused sodium acetate, triazoloquinazoline derivatives 5 - 7 were produced. In a similar manner, acetic anhydride and/or 2- chlorobenzoylcholoride were reacted with compound 4 to furnish the triazoloquinazoline derivatives 8, 9, respectively. In addition, the corresponding triazinoquinazoline derivative 11 was obtained via reaction of compound 4 with ethyl chloroacetate. The triazoloquinazoline 16 was obtained in good yield via reaction of 4 with diethyloxalate. The results of the pharmacological study indicated that some of the derivatives which were tested, especially 5, 8, 11 and 16 showed good antipyretic and anti-inflammatory activities. Also, the median lethal doses (LD50s) of compounds 5, 8, 11 and 16 in mice were 268, 208, 322 and 231 mg/100g b.w., respectively. Oral administration of compounds 5, 8, 11 and 16 to the rats at dose of 300 mg/kg.b.w. for 10 days showed non-significant changes in liver enzymes SGOT, SGPT, ALP, LDH, ? -GT, SOD and GPx and blood GSH and serum TBARs as compared with the control group. But, administration of indomethacin orally to the rats at a concentration of 600 mg/kg b.w daily for 10 days to rats showed significant increase in serum SGOT, SGPT, ALP, LDH, ? -GT and TBARs and significant decrease in blood GSH, SOD and GPx. These findings suggest that compounds 5, 8, 11 and 16 exhibited good antipyretic and anti-inflammatory activities and more safe on liver enzymes in rats.
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