Synthesis and antineoplastic activity of N,N'-disubstituted phenyl-3,6-dimethyl-1,4-dihydro-1,2,4,5-tetrazine-1,4-dicarboamide derivatives
Cai, Z.B.; Zhou, M.; Hu, W.X.; Yang, Z.Y.
Yao Xue Xue Bao 35(10): 793-796
2000
ISSN/ISBN: 0513-4870 PMID: 11372451 Document Number: 515255
To search for antineoplastic drugs with fewer side effects and improved activities, using tetrazine derivatives with different substituted groups in their phenyl rings. The title compounds have been synthesized by reacting 3,6-dimethyl-1,6-dihydro-1,2,4,5-tetrazine with substituted phenyl isocyanates in the presence of p-dimethylamino pyridine as catalyst. Eighteen new N,N'-disubstituted phenyl-3,6-dimethyl-1,4-dihydro-1,2,4,5-tetrazine-1,4-dicarboamides have been synthesized. Their structures have been confirmed by IR, 1HNMR and elemental analysis. The antineoplastic activities were screened. The structure-activity relationship has also been studied. The meta-substituted tetrazine derivatives showed marked antitumor activities against P388 and A-549 when electronic effect constants and hydrophobic constants of their substitutents are in a certain range.