Synthesis and anti-inflammatory evaluation of 3-methylthio-1,2,4-triazines, 3-alkoxy-1,2,4-triazines, and 3-aryloxy-1,2,4-triazines

Article abstract of DOI:10.1002/jps.2600690310

To develop nonacidic, nonsteroidal anti-inflammatory agents without GI complications, a series of asymmetric triazines was synthesized and evaluated for anti-inflammatory efficacy in the carrageenan-induced pedal edema assay. Toxicity was estimated by determination of approximate LD₅₀ values in mice. 25 Compounds possessed activity comparable to the standard, indomethacin. Thirteen of the 25 compounds were selected for dose-response evaluation in the carrageenan assay based on their relative toxicity and anti-inflammatory activity. Neurotoxicity of the 13 triazines was estimated by determination of NTD₅₀ values in mice. Five of the 13 compounds tested in the dose-response assay were active in terms of anti-inflammatory efficacy (ED₅₀ values) and lack of overt neurotoxicity (NTD₅₀ values) when compared to indomethacin. To determine the effect of these five developmental triazines on chronic inflammation, they were evaluated in the adjuvant-induced polyarthritis assay. One was comparable to indomethacin in reducing adjuvant-induced inflammation in this assay.