Molvi K.I., Sudarsanam V., Patel M.M., Haque N.
School of Pharmacy, Faculty of Medical Sciences, Jimma University, Jimma, Ethiopia; Department of Medicinal Chemistry, B. V. Patel Pharmaceutical Education and Research Development Centre, Ahmedabad Gujarat, India; Shree S. K. Patel College of Pharmaceutical Education and Research, Ganpat Vidayanagar, Mehsana Gujarat, India; Department of Chemistry, Faculty of Education, Jimma University, Jimma, Ethiopia
Molvi, K.I., School of Pharmacy, Faculty of Medical Sciences, Jimma University, Jimma, Ethiopia; Sudarsanam, V., Department of Medicinal Chemistry, B. V. Patel Pharmaceutical Education and Research Development Centre, Ahmedabad Gujarat, India; Patel, M.M., Shree S. K. Patel College of Pharmaceutical Education and Research, Ganpat Vidayanagar, Mehsana Gujarat, India; Haque, N., Department of Chemistry, Faculty of Education, Jimma University, Jimma, Ethiopia
A new series of tetrasubstituted thiophene analogues (4a-4f, 5a-5f and 8a-8i) were designed incorporating the pharmacophoric features of COX-1 (as in fenamates), 5-LOX and the p38 MAP kinase inhibitors. The designed series was synthesized by nucleophilic addition of aryl/ aroylisothiocyanate and enamine (2) yielding the addition product l-(α-Carbomethoxy-β-aminothiocrotonoyl)-aryl/aroyl amines (3/7); which on reaction with substituted phenacyl bromides gave the targeted tetrasubstituted thiophene esters (4a-4f/8a-8i). The tetrasubstituted thiophenes esters (4a-4f) on hydrolysis with one equivalent of potassium hydroxide solution in methanol at room temperature gave corresponding acids (5a-5f). All the targeted compounds were evaluated for their anti-inflammatory activity in carrageenin-induced rat hind paw oedema model at the doses of 10, 20 and 40 mg/kg body weight using standard drugs mefanamic acid and ibuprofen. The compounds (4c, 4e, 4f, 5f, 8a- 8i) which gave reasonable protection to the inflamed paw, eliciting good or moderate comparable anti-inflammatory activity were selected for investigating their analgesic activity using acetic acid induced writhing response test in albino mice at 10 mg/kg dose using standard drug ibuprofen and in order to arrive at possible mechanism of their anti-inflammatory activity, in vitro antioxidant nitric oxide radical scavenging assay at the concentrations of 5, 10, 15, 20, 25, 30 and 35 μg/mL were performed using standard drug ascorbic acid.
2 (4 methoxyanilino) 5 (4 nitrobenzoyl) 4 methylthiophene 3 carboxylic acid; 2 (4 methoxylanilino) 5 (3 nitrobenzoyl) 4 methylthiophene 3 carboxylic acid; 2 (4 methylanilino) 5 (3 nitrobenzoyl) 4 methylthiophene 3 carboxylic acid; 2 (4 methylanilino) 5 (4 chlorobenzoyl) 4 methylthiophene 3 carboxylic acid; 2 (4 methylanilino) 5 (4 nitrobenzoyl) 4 methylthiophene 3 carboxylic acid; 2 anilino 5 (4 nitrobenzoyl) 4 methylthiophene 3 carboxylic acid; antiinflammatory agent; ascorbic acid; ibuprofen; mefenamic acid; methyl 2 (2 furoylamino) 5 (2,4 dichlorobenzoyl) 4 methylthiophene 3 carboxylic acid; methyl 2 (2 furoylamino) 5 (3 nitrobenzoyl) 4 methylthiophene 3 carboxylic acid; methyl 2 (2 furoylamino) 5 (4 methoxybenzoyl) 4 methylthiophene 3 carboxylic acid; methyl 2 (2 furoylamino) 5 (4 nitrobenzoyl) 4 methylthiophene 3 carboxylic acid; methyl 2 (4 methoxyanilino) 5 (4 nitrobenzoyl) 4 methylthiophene 3 carboxylic acid; methyl 2 (4 methoxycanilino) 5 (3 nitrobenzoyl) 4 methylthiophene 3 carboxylic acid; methyl 2 (4 methylanilino) 5 (3 nitrobenzoyl) 4 methylthiophene 3 carboxylic acid; methyl 2 (4 methylanilino) 5 (4 chlorobenzoyl) 4 methylthiophene 3 carboxylic acid; methyl 2 (4 methylanilino) 5 (4 nitrobenzoyl) 4 methylthiophene 3 carboxylic acid; methyl 2 anilino 5 (4 nitrobenzoyl) 4 methylthiophene 3 carboxylic acid; methyl 2 benzoylanilino 5 (2,4 dichlorobenzoyl) 4 methylthiophene 3 carboxylic acid; methyl 2 benzoylanilino 5 (3 nitrobenzoyl) 4 methylthiophene 3 carboxylic acid; methyl 2 benzoylanilino 5 (4 methoxybenzoyl) 4 methylthiophene 3 carboxylic acid; methyl 2 benzoylanilino 5 (4 methylbenzoyl) 4 methylthiophene 3 carboxylic acid; methyl 2 benzoylanilino 5 (4 nitrobenzoyl) 4 methylthiophene 3 carboxylic acid; thiophene derivative; unclassified drug; analgesic activity; animal experiment; animal model; antiinflammatory activity; antioxidant activity; article; concentration response; controlled study; drug design; drug dose comparison; drug screening; drug synthesis; female; in vitro study; male; nonhuman; paw edema; priority journal; rat; writhing test; Animals; Anti-Inflammatory Agents; Antioxidants; Drug Design; Edema; Female; Male; Molecular Structure; Rats; Structure-Activity Relationship; Thiophenes; Mus; Rattus