Synthesis of novel dipyrido-1,4-thiazines

An efficient synthesis of novel type of dipyrido-1,4-thiazine (4) was elaborated in the reactions of two pairs of 3,4-disubstituted pyridines in DMF. The reactions proceeded through the S -> N type of the Smiles rearrangement of the resulting 4,4'-dipyridinyl sulfide. In the case of formation of 10-(3'-nitro-4'pyridinyl)-2,7-diazaphenothiazine (5) double rearrangement was observed. 10H-2,7-diazaphenothiazine (4) was N-alkylated, N-arylated and N-heteroarylated to give 10-substituted (alkyl, arylalkyl, aryl, heteroaryl and dialkylarninoalkyl) derivatives (5) and (17-29). The NMR spectra were assigned with the help of the H-1-H-1 correlation (COSY) and NOE experiment of the methyl derivative (17). The crucial 10H-2,7-diazaphenothiazine (4) showed promising anticancer activity.