Antiinflammatory agents. 4. Syntheses and biological evaluation of potential prodrugs of 2-amino-3-benzoylbenzeneacetic acid and 2-amino-3-(4-chlorobenzoyl)benzeneacetic acid.
A series of potential prodrugs of 2-amino-3-benzoylbenzeneacetic acid (amfenac) and 2-amino-3-(4-chlorobenzoyl)benzeneacetic acid were synthesized and evaluated for their cyclooxygenase inhibiting properties, antiinflammatory potency, and gastrointestinal irritation liability. One compound, 2-amino-3-(4-chlorobenzoyl)benzeneacetamide, possessed a therapeutic index 1 order of magnitude greater than that of indomethacin.
Walsh
D A
DA
Department of Chemical Research, A.H. Robins Company, Richmond, Virginia 23261-6609.
Moran
H W
HW
Shamblee
D A
DA
Welstead
W J
WJ
Nolan
J C
JC
Sancilio
L F
LF
Graff
G
G
D000081:Acetamides / Q000138:chemical synthesis / Q000627:therapeutic use / Q000633:toxicity; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity; D001169:Arthritis, Experimental / Q000188:drug therapy; D044482:Benzeneacetamides; D002351:Carrageenan; D055598:Chemical Phenomena; D002621:Chemistry; D016861:Cyclooxygenase Inhibitors; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D007213:Indomethacin / Q000627:therapeutic use; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy; D008297:Male; D015394:Molecular Structure; D010648:Phenylacetates / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity; D011355:Prodrugs / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity; D051381:Rats
D000081:Acetamides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D044482:Benzeneacetamides; D016861:Cyclooxygenase Inhibitors; D010648:Phenylacetates; D011355:Prodrugs; C014285:amfenac; C020177:AHR 6293; C065064:AHR 10037; D002351:Carrageenan; D007213:Indomethacin