In the present study, the effects of subchronic treatments (4 weeks) of hypercholesterolemic (single) and diabetic-hypercholesterolemic (combined) rats with 4 (3H) quinazolinone and 2 halogenated derivatives (6, 8-dibromo-2-methy-4 (3H) quinazolinone and 6-iodo-2-methyl-4(3H) quinazolinone) at a sublethal dose level (2 mg/Kg) on cholesterol metabolism were investigated. Bezafibrate, a hypolipidemic drug was used as a reference compound for data comparison. Treatment of rats with single and combined hypercholesterolemia with quinazolinone compounds gave rise to highly significant reductions in serum total cholesterol and cholesterol ester levels, whereas serum triacylglycerol level was significantly reduced only after treatment with halogen-substituted quinazolinones in single hyper-cholesterolemia, compared to the control group. The effects of different quinazolinones and bezafibrate on reduction of serum LDL-C level were comparable in single hypercholesterolemia but significantly different in combined hypercholesterolemia. Results obtained from this study suggest that the antihyperlipidemic effect of quinazolinone compounds was brought about by inhibition of dietary cholesterol absorption and / or intestinal ACAT activity.

The reaction of α‐cyanothioacetamide (1) or its methylthio derivative (2) with anthranilic acid led to the formation of 3,4‐dihydro‐4‐oxoquinazolin‐2‐yl acetonitrile (3). 3 condensed with aromatic aldehydes to give arylidene derivatives (4a‐d) which could be prepared also via the reaction of 2‐thiocarbamoylcinnamonitriles (5a‐d) or their methylthio derivatives (6a‐d) with anthranilic acid. 3 reacted with cinnamonitrile derivatives (7a‐h) and (12a‐d) to yield pyrido‐[1,2‐a]‐quinazoline derivatives (10a‐h) and (15a‐d) which could also be prepared by the reaction of (4a‐d) with malononitrile (11a), benzoyl acetonitrile (11b) and ethylcyanoacetate (16), respectively.

3‐Arylacrylonitrile‐2‐thiocarboxamides (1a–d) reacted with S‐methylisothiourea to give 4‐amino‐6‐aryl‐2‐methylmercaptopyrimidine‐5‐carbonitriles (3a–d). The products 3a–d were also obtained via the reaction of 3‐arylacrylonitrile‐2‐carbonitriles (4a–d) with S‐methylisothiourea. Compounds 4a–d reacted with thiourea and urea to yield 4‐amino‐6‐aryl‐2‐mercaptopyrimidine‐5‐carbonitriles (5a–d) and 2‐hydroxy derivatives (5e–h) respectively. Oxidation of 5a–d with hydrogen peroxide afforded 5e–h. 5a–h were readily alkylated with methyl iodide to give 3a–d.

Coupling of the diazonium salts (IV) with the thiazole (III), prepared by cyclocondensation of cyanothioacetamide (I) with thioglycolic acid (II), yields the mono‐ and diarylazo derivatives (V) and (VI).

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