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 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)-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 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.

Recent Developments and Multiple Biological Activities Available With 1, 8-Naphthyridine Derivatives: A Review

“…Development and advancement in new antimicrobial drugs are yet in the demand of the day due to microbial resistance, whereby 1, 8-Naphthyridines are imperative components in novel antibacterial drug discovery [28][29][30]. Gohil et al [31] synthesize new chromeno [4,3-f] [1,8] naphthyridines analogs (14a-d) by a multicomponent reaction and evaluate for their antimicrobial activity. The compounds with 4-fluorophenyl (14a),3-trifluoromethyl (14b), 6-Amino-8-(4-fluorophenyl) (14c) and 6-Amino-12-methoxy-8-(3-(trifluoro-methyl)phenyl)-(14d) shows excellent antimicrobial activity against both type of bacterial strains with MIC value 50 mg/ml, and also the compounds (14a) and (14c) exhibit excellent antifungal activity with MIC value 250 mg/ml.…”

“…Acosta et al [45] synthesize various 1, 8-naphthyridine derivatives by microwave-assisted synthesis with heterocyclic o-aminonitriles and cyclic ketenes catalyzed by ZnCl2 and produce a series of pyrazolo [3,4-b] [1,8] naphthyridine-5-amines. The derivatives with a 4-p-tolyl substituent at naphthyridine skeleton (35a, 35b and 35c) are most active against C. albicans, which appear to be linked with their corresponding hydrophobicity.…”

“…Takayama et al [118] prepare new and phosphodiesterase (PDE4) inhibitor. The compounds show selective inhibitory activities against PDE4 obtained from human peripheral blood cells and are inactively applicable to other PDE types (1,2,3,5). The compound 4, 5, 7-Trimethyl-1-phenyl-1, 8-naphthyridine-2 (1H)-one (99)-YM-10335) having 1, 8-naphthyridine-2 (1H)-one skeleton completely differ structurally from rolipram and is selected as a lead compound.…”

“…Stuk et al [123] study the NPTR derivatives having different moieties (102) for anxiolytic activity which may be due to the partial agonist action of benzodiazepine at the site of the GABAA receptor. Lorrio et al [124] investigate the neuroprotective profile of ethyl 5-amino-2-methyl-6, 7, 8, 9-tetrahydro benzo [b] [1,8] naphthyridine-3-carboxylic acid ester (103-ITH12246) through in vitro models for Alzheimer's disease. They also find the pharmacological activities of ITH12246 and evaluate its capacity to counter the memory mutilation elicited by scopolamine, a muscarinic antagonist characterized to approve memory loss.…”

“…Nowadays, researchers are concentrating interests towards the introduction of novel and safe therapeutic agents for getting medical significance [1]. The nitrogen-containing heterocycles are the major class of chemical compounds in therapeutic uses.…”