Study On The Synthesis Of 3,6-dialkyl-s-tetrazine Derivatives And The Antitumor Activity

Cancer is the principle disease that endangers human's life. At present the research of antitumor drugs is one of the main field of scientific development. This dissertation is chiefly engaged in studying on the synthesis of tetrazine derivatives, and inspecting its antitumor activities.This dissertation study on the synthesis of 3,6-dialkylhexahydro-s-tetrazine and its derivatives. Four hexahydro-s-tetrazines and its four 1,4-diacyl derivatives were synthesized. The reaction mechanism was proposed. The research on the synthesis of 3,6-diarylhexahydro-s-tetrazine have been taken,and we found that it could not form the compounds from the reaction of azine with hydrazine.Twenty six compounds were synthesized via the reaction of 1,6-dihydro-s-tetrazine with chloride formate,substituted phenyl isocyanate and anhydride. The 'HNMR of monosubstituted 1,6-dihydro-s-tetrazine derivatives was discussed.In the presence of DMAP,eight N,N' -disubstituted phenyl-3,6-dialkyl-l,4-dihydro -s-tetrazine-l,4-dicarboamides were synthesized. By the analysis of the crystal structure,we found that this kind of derivatives showed a boat conformation.The antitumor activity in vitro was evaluated. The results show that monosubstituted derivatives of 1,6-dihydro-s-tetrazine display some antitumor activities. When the concentration become diluted, the antitumor antivity disceased quickly. 1,4-diacyl -3,6- dialkylhexahydro-s-tetrazine had little antitumor activity even in high concentration.The antitumor activity of N,N" -disubstituted phenyl-3,6-dialkyl -l,4-dihydro-s-tetrazine-l,4-dicarboamides is the best.