A SULFONAMIDO-INDANONE DERIVATIVE CGP-28237 (ZK-34228), A NOVEL NONSTEROIDAL ANTIINFLAMMATORY AGENT WITHOUT GASTROINTESTINAL ULCEROGENICITY IN RATS

  • 1 January 1987
    • journal article
    • research article
    • Vol. 13  (5) , 237-245
Abstract
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 .apprx. 0.5 mg/kg p.o.) and good activity in carrageenin oedema (ED40 .apprx. 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 .times. 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 .apprx. 3 .times. 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.