Etodolic acid and related compounds. Chemistry and antiinflammatory actions of some potent di- and trisubstituted 1, 3, 4, 9-tetrahydropyrano[3, 4-b]indole-1-acetic acids.
A series of 37 1-ethyl- and 1-n-propyl-1, 3, 4, 9-tetrahydropyrano[3, 4-b]indole-1-acetic acids bearing one, or two, substituents on the benzene ring has been synthesized via the acid-catalyzed condensation of a substituted tryptophol with ethyl propionylacetate or ethyl butyrylacetate. Antiinflammatory and ulcerogenic effects were examined and the results show that 1, 8-diethyl-1, 3, 4, 9-tetrahydropyrano[3, 4-b]indole-1-acetic acid (etodolic acid, USAN) is a potent agent, particularly active against a chronic rat model of inflammation (ED50 0.7 + 1-0.1 mg/kg po in the adjuvant arthritis model) and which has a relatively low acute ulcerogenic potential in the same species.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000138:chemical synthesis* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D002351:Carrageenan; D005620:Freund's Adjuvant; D007210:Indoleacetic Acids / Q000009:adverse effects / Q000138:chemical synthesis* / Q000627:therapeutic use; D008297:Male; D011714:Pyrans / Q000009:adverse effects / Q000138:chemical synthesis / Q000627:therapeutic use; D051381:Rats; D013276:Stomach Ulcer / Q000139:chemically induced
D000893:Anti-Inflammatory Agents; D007210:Indoleacetic Acids; D011714:Pyrans; D002351:Carrageenan; D005620:Freund's Adjuvant