Application of 3-methylthiopyrido[4,3-e]-1,4,2-dithiazine 1,1-dioxide to the synthesis of novel series of 4H-pyrido[4,3-e]-1,2,4-thiadiazine derivatives with potential biological activity

Two series of 4H‐pyrido[4,3‐e]‐1,2,4‐thiadiazine derivatives 3, 4, 5 and 7, 8, 9, 10, 11, 12 were synthesized by the reactions of 3‐methylthiopyrido[4,3‐e]‐1,4,2‐dithiazine 1,1‐dioxide 1 with 2‐or 6‐hydrazinoazines and 2‐aminophenols or 2‐aminothiophenol, respectively. Aminolysis of 8 (R = Me, Y = O) afforded the corresponding 3‐(R‐amino)‐4‐(2‐hydroxy‐5‐methylphenyl)‐4H‐pyrido[4,3‐e]‐1,2,4‐thiadiazine 1,1‐dioxides 13, 14, 15, 16, 17, 18. The structures of these compounds were confirmed on the basis of elemental analysis, spectral data, and X‐ray crystallography. Compounds 3, 4, 5, 7, 8, 9, 10, 12, 13, 14, 15, and 17, 18 were screened in vitro for antibacterial activity. Moreover, preliminary in vitro anticancer assay was performed for compounds 3, 7, 10, 11, 12, 13, and 17, 18 at the National Cancer Institute (Bethesda, MD) at a single dose (10 μM) in the full NCI 60 cell panel. J. Heterocyclic Chem., (2009).