Patent Evaluation: Novel Dual 5-LPO/CO Inhibitors

Summary

Novelty: Novel compounds which are 4,6-di-t-butyl-5-hydroxy-1,3-pyrimidine substituted 1,2,4- and 1,3,4-thiadiazoles and oxadiazoles, and 1,2,4-triazoles, together with pharmaceutical compositions containing these compounds, are disclosed. These compounds are inhibitors of 5-LPO and/or CO. They are potentially useful for treating conditions such as inflammation, arthritis, pain, GI ulcers etc. These compounds are also potentially useful as antioxidants; however, the preferred use is in treating inflammatory conditions. A method for manufacturing a pharmaceutical composition containing these compounds is given.

Biology: The efficacy of the compounds as inhibitors of 5-LPO and CO was demonstrated using the carrageenan-induced rat foot paw oedema-2 (CFE-2) assay, the mycobacterium-induced rat foot pad oedema assay (MFE) and various other tests. However, no specific biological data are presented.

Chemistry: Twenty-four compounds are exemplified. One compound is most preferred and six intermediate compounds are preferred.

Structure: