A sulphonamido-indanone derivative CGP 28237 (ZK 34228), a novel non-steroidal anti-inflammatory agent without gastro-intestinal ulcerogenicity in rats.
CGP 28237 (5-methylsulphonylamino-6-phenoxy-1-indanone) belongs to a series of structurally novel indanones. The compound is a weak acid (pK = 6.98), but it does not contain a carboxylic group. CGP 28237 exhibits potent anti-inflammatory activity in developing and established adjuvant arthritis in rats (ED40 approximately 0.5 mg/kg p.o.) and good activity in carrageenin oedema (ED40 approximately 3 mg/kg p.o.). It inhibits yeast-induced fever in rats with ED50 values of 1, 2 and 10 mg/kg p.o. at 1, 3 and 5 hours after drug administration. The antinociceptive activity in mice (phenyl-p-benzoquinone writhing) and rats (acetic-acid writhing) is weak. CGP 28237 has been shown to be non-ulcerogenic in rats under acute and chronic test conditions: it does not cause mucosal lesions in the stomach at 2 X 400 mg/kg p.o., it does not enhance gastro-intestinal blood loss during 10 days' oral treatment with 400 mg/kg p.o., and it did not induce gastro-intestinal lesions in a 4-week toxicity study up to 1000 mg/kg p.o. Although CGP 28237 is not a cyclooxygenase inhibitor in bovine seminal vesicle microsomes, it inhibits prostaglandin synthesis in zymosan-stimulated murine macrophages (IC50 approximately 3 X 10(-6) mol/l) and protects rabbits against arachidonic acid-induced lung embolism with 10 mg/kg p.o. CGP 28237 may represent a novel anti-inflammatory drug with excellent gastro-intestinal tolerability.
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D001095:Arachidonic Acids / Q000378:metabolism; D001169:Arthritis, Experimental / Q000188:drug therapy; D004361:Drug Tolerance; D004487:Edema / Q000188:drug therapy; D005260:Female; D005334:Fever / Q000188:drug therapy; D007189:Indans / Q000494:pharmacology* / Q000627:therapeutic use; D007192:Indenes / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009780:Occult Blood; D011655:Pulmonary Embolism / Q000188:drug therapy; D011817:Rabbits; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000139:chemically induced*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001095:Arachidonic Acids; D007189:Indans; D007192:Indenes; C054253:5-methylsulfonylamino-6-phenoxy-1-indanone