Design, synthesis and pharmacological evaluation of some novel 2-(4-nitrophenyl)-3-methylthio-3-(substituted)arylamino acrylamides as potential anti-inflammatory agents.
On the basis of structure based drug design we have designed a series of 2-(4-nitrophenyl)-3-methylthio-3-(substituted)arylamino acrylamides as potential antiinflammatory agents. Good 3D similarity was observed between the designed molecule and rofecoxib (r.m.s.d. 0.161). The effect of opening the central ring and introducing a spacer (-NH-) between one of the aryl rings and the central ring of the basic structure of the COX-2 inhibitors was also studied. The designed molecules were synthesised by thiocarbomylation of the 4-nitro-phenylacetamide with aryl isothiocyanates followed by subsequent methylation of the enethiolate salts. All compounds were screened for their antiinflammatory activity by the carrageenan induced rat paw edema method. Compounds 4 and 6 exhibited potent antiinflammatory activity, which was found to be comparable with the standard drug, rofecoxib. Both the potent molecules were also screened for their ulcerogenic potential in Albino rats. A very low ulcer index was observed with both compounds, although higher than rofecoxib.
Chhabria
M T
MT
L. M. College of Pharmacy, Navrangpura, Ahmedabad, Gujarat, India. mt_chhabria@icenet.net
Patel
C K
CK
Jani
M H
MH
D000178:Acrylamides / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology*; D002351:Carrageenan; D015195:Drug Design; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D007202:Indicators and Reagents; D008958:Models, Molecular; D009574:Nitro Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D013276:Stomach Ulcer / Q000139:chemically induced; D013329:Structure-Activity Relationship
D000178:Acrylamides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007202:Indicators and Reagents; D009574:Nitro Compounds; D002351:Carrageenan