Synthesis, characterization and pharmacological evaluation of substituted phenoxy acetamide derivatives/Sinteza, karakterizacija i farmakoloska evaluacija supstituisanih derivata fenoksiacetamida

A novel series of 2-(substituted phenoxy)-W-(1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)acetamide and W-(2-bromocyclohexyl)-2-(substituted phenoxy)acetamide derivatives having cyclohexyl nucleus as common in both types were synthesized and assessed for their antiinflammatory 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 and 1b. These amines on further chloroacetylation with chloroacetylchloride give compounds 2a and 2b. Compounds 2a and 2b are converted to 2-(substituted phenoxy)-W-(1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl) acetamide and W-(2-bromocyclohexyl)-2-(substituted phenoxy)acetamide derivatives on treatment with substituted phenol. Among the series 3a-f, 3i, 3k and 3l compounds showed significant anti-inflammatory activity as compared to the standard drug diclofenac sodium and also compounds 3a-f, 3h, 3j and 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)-W-(1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)acetamide, W-(2-bromocyclohexyl)-2-(substituted phenoxy)acetamide, anti-inflammatory activity, analgesic activity, antipyretic activity. Nove serije 2-(supstituisanih fenoksi)-N-(1,7,7-trimetilbiciklo[2.2.1]heptan-2-il)acetamida i derivata N-(2-bromocikloheksil)-2-(supstituisanih fenoksi)acetamida koji sadrze cikloheksanski prsten su sintetizovane i ispitivane u cilju odredivanja njihove antiinflamatorne aktivnosti, analgetske aktivnosti i antipiretickog dejstva. Sva nova jedinjenja su sintetizovana reakcijom kamfora ili slicnih ketona, koji sadrze cikloheksanski prsten (na primer 2-bromocikloheksanon), sa amonijum-karbonatom i mravljom kiselinom, pri cemu su se kao krajnji proizvod dobili aromaticni amini 1a i 1b. Ovi amini su hloroacetilovanjem pomocu hloroacetilhlorida dali jedinjenja 2a i 2b. Jedinjenja 2a i 2b su prevedena u 2-(supstituisane fenoksi)-N-(1,7,7-trimetilbiciklo[2.2.1]heptan-2-il)acetamide i N-(2-bromocikloheksil)-2-(supstit