Antiinflammatory 2,6-di-tert-butyl-4-(2-arylethenyl)phenols.
A series of 2,6-di-tert-butyl-4-(2-arylethenyl)phenols was prepared and examined for their ability to inhibit cyclooxygenase and 5-lipoxygenase in vitro and developing adjuvant arthritis in vivo in the rat. Structure-activity relationships are discussed. Among the best compounds is (E)-2,6-di-tert-butyl-4-[2-(3-pyridinyl)ethenyl]phenol (7d). It has an IC50 of 0.67 microM for cyclooxygenase and 2.7 microM for 5-lipoxygenase and an ED50 of 2.1 mg/kg in developing adjuvant arthritis. Additional in vivo data are reported for 7d.
Lazer
E S
ES
Department of Medicinal Chemistry, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut 06877.
Wong
H C
HC
Possanza
G J
GJ
Graham
A G
AG
Farina
P R
PR
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000188:drug therapy; D055598:Chemical Phenomena; D002621:Chemistry; D016861:Cyclooxygenase Inhibitors; D004353:Drug Evaluation, Preclinical; D004487:Edema / Q000188:drug therapy; D016859:Lipoxygenase Inhibitors; D008297:Male; D010636:Phenols / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D013343:Styrenes / Q000138:chemical synthesis* / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D010636:Phenols; D013343:Styrenes; C058105:2,6-di-tert-butyl-4-(2-(3-pyridinyl)ethenyl)phenol