Novel 1,2,4-oxadiazoles and 1,2,4-thiadiazoles as dual 5-lipoxygenase and cyclooxygenase inhibitors.

Abstract

A series of 1,2,4-oxadiazoles and 1,2,4-thiadiazoles containing a 2,6-di-tert-butylphenol substituent were prepared and evaluated as dual inhibitors of 5-lipoxygenase and cyclooxygenase in rat basophilic leukemia (RBL-1) cells. Several of these compounds show oral efficacy in the rat carrageenan footpad edema (CFE) and mycobacterium footpad edema (MFE) antiinflammatory models, without concomitant gastric ulceration. Structure-activity relationships are discussed. The best compounds (ID40 values in MFE of 3-8 mg/kg po) contain guanidine-derived substituents on the heterocyclic ring.

• Authors: P C Unangst, G P Shrum, D T Connor, R D Dyer, D J Schrier
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 35 Issue 20 Pg. 3691-8 (Oct 02 1992) ISSN: 0022-2623 [Print] United States
• PMID: 1433181 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents
• Anti-Inflammatory Agents, Non-Steroidal
• Cyclooxygenase Inhibitors
• Enzyme Inhibitors
• Lipoxygenase Inhibitors
• Oxadiazoles
• Thiadiazoles

Topics

• Animals
• Anti-Inflammatory Agents
• Anti-Inflammatory Agents, Non-Steroidal (chemical synthesis)
• Cyclooxygenase Inhibitors (chemical synthesis, pharmacology)
• Enzyme Inhibitors (chemical synthesis)
• Lipoxygenase Inhibitors
• Male
• Oxadiazoles (chemical synthesis, pharmacology)
• Rats
• Rats, Wistar
• Structure-Activity Relationship
• Thiadiazoles (chemical synthesis, pharmacology)
• Tumor Cells, Cultured (drug effects, metabolism)