Synthesis, spectral studies and anti-inflammatory activity of glycolamide esters of niflumic acid as potential prodrugs.
In order to reduce the gastric irritation caused by direct contact mechanism of the carboxylic acid group, a series of glycolamide esters of niflumic acid (CAS 4394-00-7) (1) have been prepared as bio-labile prodrugs by reacting appropriate 2-chloroacetamides with niflumic acid. The required 2-chloroacetamides were obtained by the condensation of chloroacetyl chloride and corresponding amine. Their structures were confirmed by UV, IR and 1H NMR spectra. Selected compounds were evaluated for anti-inflammatory activity in carrageenan induced paw oedema in rats at the doses of 45, 90 and 150 mg/kg b.w. Prodrugs showed comparable anti-inflammatory activity (67.1-79.4%) at 150 mg/kg b.w. with respect to niflumic acid (70.3%) at 45 mg/kg b.w., indicating moderate release of niflumic acid in vivo. The highest activity was observed with diethylamine (4) and pyrrolidine (9) derivatives.
Gadad
Andanappa K
AK
Department of Medicinal Chemistry, College of Pharmacy, Jawaharlal Nehru Medical College, Belgaum, Karnataka, India. akgadad@rediffmail.com
Bhat
Shailija
S
Tegeli
Varsha S
VS
Redasani
Vivek V
VV
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology*; D002351:Carrageenan; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D005260:Female; D007202:Indicators and Reagents; D008297:Male; D009544:Niflumic Acid / Q000138:chemical synthesis* / Q000494:pharmacology*; D011355:Prodrugs / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007202:Indicators and Reagents; D011355:Prodrugs; D009544:Niflumic Acid; D002351:Carrageenan