2-Amino-5-thiazolyl motif: A novel scaffold for designing anti-inflammatory agents of diverse structures

• Published in: European journal of medicinal chemistry Vol. 43; no. 1; pp. 129 - 134
• Main Authors: Franklin, P.X., Pillai, Ajay D., Rathod, Parendu D., Yerande, Swapnil, Nivsarkar, Manish, Padh, Harish, Vasu, Kamala K., Sudarsanam, V.
• Format: Journal Article
• Language: English
• Published: ISSY-LES-MOULINEAUX Elsevier Masson SAS 2008; Elsevier
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - chemical synthesis; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Anti-Inflammatory Agents, Non-Steroidal - toxicity; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Carrageenan - toxicity; Carrageenin; Chemistry, Medicinal; Chronic Disease - drug therapy; Cyclooxygenase Inhibitors - metabolism; Drug Design; Edema - chemically induced; Edema - drug therapy; Female; Foot - pathology; Formaldehyde - toxicity; Formalin; Inflammation; Inflammation - drug therapy; Inflammation - pathology; Life Sciences & Biomedicine; Male; Medical sciences; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Science & Technology; Thiazole; Thiazoles - chemical synthesis; Thiazoles - pharmacology; Thiazoles - therapeutic use; Thiazoles - toxicity; Formalin; Inflammation; Carrageenin; Thiazole; formalin; inflammation; carrageenin; thiazole; Rat; Sulfone; Toxicity; Thiazole derivatives; Rodentia; Antiinflammatory agent; Oxime; Biological activity; Vertebrata; Gastroduodenal; Mammalia; Animal; Carboxamide; Benzamide derivatives; Ulcer; Chemical synthesis
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2007.02.008

Substituted thiazoles with different structural features were synthesized and screened for their anti-inflammatory activity in acute carrageenin induced rat paw edema model and chronic formalin induced rat paw edema model. The compounds 1– 5 showed 83, 30, 63, 69 and 73% protection, respectively, in acute carrageenin induced rat paw edema model. In 5-day chronic formalin induced rat paw edema model on the fifth day 1 and 5 gave 66 and 41% protection. Both studies were carried out at a dose of 100 mg/kg body weight. The activity was compared with that of Ibuprofen, Rofecoxib, and Dexamethasone both in acute and chronic anti-inflammatory models. Compound 1 without COX-1 and COX-2 inhibitory activity showed good activity profile almost mimicking the gold standard Dexamethasone in terms of efficacy. A 7-day study in rats at dose of 100 mg/kg showed that this compound does not have any ulcerogenic activity and toxicity. The activity of 5 shows that incorporating two pharmacophoric features in one molecule can be a good drug designing strategy. 2,4-Diaminothiazoles with an aliphatic oxime esters attached via a ketone bridge to the 5th position of thiazole was identified as a novel scaffold for designing anti-inflammatory agents. [Display omitted]