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

Franklin PX, Pillai AD, Rathod PD, Yerande S, Nivsarkar M, Padh H, Vasu KK, Sudarsanam V

Medicinal Chemistry Department, B. V. Patel Pharmaceutical Education and Research Development Centre, Thaltej-Gandhinagar Highway, Thaltej, Ahmedabad, Gujarat 380 054, India.

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 100mg/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 100mg/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.

Published 21 January 2008 in Eur J Med Chem, 43(1): 129-34.
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