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)
|