Design and synthesis of quinazolinyl acetamides for their analgesic and anti-inflammatory activities

Abstract

A variety of novel 2-(substituted)-N-(4-oxo-2-phenylquinazolin-3(3H)-yl)acetamides were synthesized by the reaction of 2-chloro-N-(4-oxo-2-phenylquinazolin-3(3H)-yl)acetamide with various amines. The starting material, 2-chloro-N-(4-oxo-2-phenylquinazolin-3(3H)-yl) acetamide, was synthesized from anthranilic acid by the multistep process. The title compounds were investigated for analgesic, anti-inflammatory, and ulcerogenic index activities. Among those, the compound 2-(ethylamino)-N-(4-oxo-2-phenylquinazolin-3(3H)-yl) acetamide (V9) showed most potent analgesic and antiinflammatory activities of the series and it is moderately more potent compared to the reference standard diclofenac sodium. Interestingly, the test compounds showed only mild ulcerogenic potential compared to aspirin.

Synthesis and cytotoxic evaluation of some derivatives of triazole-quinazolinone hybrids

“…Then quinazoline derivatives were treated with chloroacetyl chloride in the presence of dichloromethane/triethylamine to afford the 2-chloro -N-(4-oxo-2-quinazolin3 (3H)-yl) acetamide derivatives. Final products were synthesized by the reaction of 2-chloro -N-(4-oxo-2-quinazolin3 (3H)-yl) acetamide derivatives with 4-mehyl-4-H-1, 2, 4-triazole- 3-thiol in dry acetone and potassium carbonate (1920).…”

Synthesis and cytotoxic evaluation of some quinazolinone- 5-(4-chlorophenyl) 1, 3, 4-oxadiazole conjugates

“…Treatment of 3-amino quinazolinone with chloro acetylchloride in the presence of dichloromethane/triethylamine afforded 2-chloro -N-(4-oxo-2-quinazolin3 (3H)-yl) acetamide derivatives ( 5a-5c ). Final compounds ( 6a-6c ) obtained through the nucleophilic displacement of the chloride with thiol of 5-(4-chlorophenyl) 1, 3, 4- oxadiazole-2-thiol in dry acetone and potassium carbonate (Scheme 1) (2122).…”

“…A mixture of related benzoxazone 3a-3c (0.01 mol) and hydrazine hydrate (0.02 mol) in ethanol was refluxed for 3 h. After the reaction was completed, the mixture was cooled and the separated solid was collected by filtration and recrystallized from ethanol or isopropanol (2122).…”

“…Then the reaction mixture was poured into ice water and extracted with dichloromethane and ethyl acetate. The extracted ethyl acetate was washed with sodium bicarbonate solution (3%) and dried over anhydrous magnesium sulfate, which upon evaporation afforded the products 5a-5c (2122).…”

“…Title compounds 6a-6c were synthesized by refluxing 2-chloro -N-(4-oxo-2-quinazolin3 (3H)-yl) acetamide derivatives 5a-5c (0.01 mol) with 5-(4-chlorophenyl) 1, 3, 4-oxadazole-2- thiol in dry acetone (20 mL) and anhydrous potassium carbonate (0.01 mmol) for 6 h. The reaction mixture was filtered while hot. The organic solution was concentrated and purified by preparative TLC (2122).…”