Antiinflammatory 2,6-di-tert-butyl-4-(2-arylethenyl)phenols

E S Lazer; H C Wong; G J Possanza; A G Graham; P R Farina

doi:10.1021/jm00121a021

Antiinflammatory 2,6-di-tert-butyl-4-(2-arylethenyl)phenols

J Med Chem. 1989 Jan;32(1):100-4. doi: 10.1021/jm00121a021.

Authors

E S Lazer¹, H C Wong, G J Possanza, A G Graham, P R Farina

Affiliation

¹ Department of Medicinal Chemistry, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut 06877.

PMID: 2491889
DOI: 10.1021/jm00121a021

Abstract

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.

MeSH terms

Animals
Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
Anti-Inflammatory Agents, Non-Steroidal / pharmacology
Arthritis, Experimental / drug therapy
Chemical Phenomena
Chemistry
Cyclooxygenase Inhibitors
Drug Evaluation, Preclinical
Edema / drug therapy
Lipoxygenase Inhibitors
Male
Phenols / chemical synthesis*
Phenols / pharmacology
Rats
Structure-Activity Relationship
Styrenes / chemical synthesis*
Styrenes / pharmacology

Substances

Anti-Inflammatory Agents, Non-Steroidal
Cyclooxygenase Inhibitors
Lipoxygenase Inhibitors
Phenols
Styrenes
2,6-di-tert-butyl-4-(2-(3-pyridinyl)ethenyl)phenol