New compounds derived from dihydropyrazines having DNA strand-breakage activity

Article abstract of DOI:10.1016/S0040-4020(98)01079-5

Dihydropyrazine derivatives such as 2,3-dihydro-5,6-dimethylpyrazine (1), 2,3-dihydro-2,5,6-trimethylpyrazine (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 stereoisomeric 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.