New compounds derived from dihydropyrazines having DNA strand-breakage activity

Dihydropyrazine derivatives such as 2,3-dihydro-5,6-dimethylpyrazine (1), 2,3-dihydro-2,5,6-trimethyl-pyrazine (2) and 2,3-dihydro-2,2,5,6-teramethylpyrazine (3) were found to be transformed into (2R∗, 3S∗, 5R∗)-1,2 ethylene-imino-1,7,10-triaza-2,3,6-trimethyl-3-hydroxy-spiro [4,5] decan-6-ene (4), the stereo-isomeric mixtures of 2,4aR∗,7,9aS∗-tetramethylcyclohexano [1,2-e: 4,5-e′]-dipiperazin-6-ene (5) and (4aR∗, 9aS∗)-2,2,4a,7,7,9a-hexamethylcyclohexano [1,2-e: 4,5-e′]-dipiperazin-6-ene (6), respectively. These dimerized compounds (4, 5 and 6), whose structures were determined by X-ray and nmr spectral analyses, showed almost the same DNA strand-breakage activity as their parent dihydropyrazines. The dimerization pathway is discussed on the basis of the PM3 calculation data.