Anti-inflammatory activity and PGE2 inhibitory properties of novel phenylcarbamoylmethyl ester-containing compounds.
A variety of 4-(un)substituted phenylcarbamoyl methyl ester-containing compounds 3a-d, 5a-d and 7a-d were synthesized via reaction in N,N-dimethylformamide of (un)substituted chloroacetanilides 2a-d with the potassium salts of ibuprofen (1), naproxen (4) and N-acetylanthranilic acid (6). Moreover, other 4-(un)substituted phenylcarbamoylmethyl ester-containing compounds 10a-d were synthesized via the attack of (un)substituted chloroacetanilides 2a-d on one of the carboxylic acid groups of the potassium salt of 4-(2-carboxyethylcarboxamido)benzoic acid (8)in N,N-dimethylformamide, with subsequent cyclization of the other one giving finally a pyrrolidinone structure. Anti-inflammatory properties of the synthesized compounds were evaluated in vivo utilizing a standard acute carrageenan-induced paw oedema method in rats and the most promising prepared anti-inflammatory active agents were evaluated for ulcerogenic liability in rats using ibuprofen and naproxen as reference standards in both screenings. PGE(2) inhibitory properties of the highly promising anti-inflammatory agents synthesized and low gastric ulcerogenic liabilities were tested with a PGE(2)assay kit technique.
Barsoum
Flora
F
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Eini Street, Cairo 11562, Egypt.
Georgey
Hanan
H
Abdel-Gawad
Nagwa
N
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000378:metabolism; D015232:Dinoprostone / Q000037:antagonists & inhibitors*; D004952:Esters / Q000737:chemistry / Q000378:metabolism; D005260:Female; D008297:Male; D015394:Molecular Structure; D048448:Phenylcarbamates / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000893:Anti-Inflammatory Agents; D004952:Esters; D048448:Phenylcarbamates; D015232:Dinoprostone