2-Amino-5-thiazolyl motif: a novel scaffold for designing anti-inflammatory agents of diverse structures.
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.
Franklin
P X
PX
Medicinal Chemistry Department, B. V. Patel Pharmaceutical Education and Research Development Centre, Thaltej-Gandhinagar Highway, Thaltej, Ahmedabad, Gujarat 380 054, India.
Pillai
Ajay D
AD
Rathod
Parendu D
PD
Yerande
Swapnil
S
Nivsarkar
Manish
M
Padh
Harish
H
Vasu
Kamala K
KK
Sudarsanam
V
V
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D002351:Carrageenan / Q000633:toxicity; D002908:Chronic Disease / Q000188:drug therapy; D016861:Cyclooxygenase Inhibitors / Q000378:metabolism; D015195:Drug Design; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D005260:Female; D005528:Foot / Q000473:pathology; D005557:Formaldehyde / Q000633:toxicity; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D013844:Thiazoles; D005557:Formaldehyde; D002351:Carrageenan