Synthesis, characterization and pharmacological evaluation of substituted phenoxy acetamide derivatives

Abstract

A novel series of 2-(substituted phenoxy)-N-(1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)acetamide and N-(2-bromocyclohexyl)-2-(substituted phenoxy)acetamide derivatives having cyclohexyl nucleus as common in both types were synthesized and assessed for their anti-inflammatory activity by a carrageenan induced rat paw oedema method, analgesic activity by Eddy’s hot plate method and antipyretic activity by brewer’s yeast induced pyrexia method. All the novel derivatives have been synthesized by the reaction of camphor and similar ketone having cyclohexane nucleus (e.g. 2-bromocyclohexanone) with ammonium carbonate and formic acid resulting in the formation of aromatic amines (1a-b). These amines on further chloroacetylation with chloroacetylchloride give compounds (2a-b). Compounds (2a-b) are converted to 2-(substituted phenoxy)-N-(1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl) acetamide and N-(2-bromocyclohexyl)-2-(substituted phenoxy)acetamide derivatives on treatment with substituted phenol. Among the series 3a-f, 3i, 3k, 3l compounds showed significant anti-inflammatory activity as compared to the standard drug diclofenac sodium and also compound 3a-f, 3h, 3j, 3k exhibit significant analgesic activity as compared to the standard drug. Compounds 3a-f and 3k showed antipyretic activity nearly to the standard drug indomethacin. Compounds 3a-f and 3k possess anti-inflammatory, analgesic and antipyretic activities near to the standard.

Keywords

• 2-(substituted phenoxy)-N-(1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)acetamide
• N-(2-bromocyclohexyl)-2-(substituted phenoxy)acetamide
• anti-inflammatory activity
• analgesic activity
• antipyretic activity