title: [Synthesis and antineoplastic activity of N,N'-disubstituted phenyl-3,6-dimethyl-1,4-dihydro-1,2,4,5-tetrazine-1,4-dicarboamide derivatives].
abstract: OBJECTIVE
  To search for antineoplastic drugs with fewer side effects and improved activities, using tetrazine derivatives with different substituted groups in their phenyl rings.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Fine Chemistry, Zhejiang University of Technology, Hangzhou 310032, China. caizb-h@163.net
authors.forename: Z B
authors.initials: ZB
authors.lastname: Cai
authors.forename: M
authors.initials: M
authors.lastname: Zhou
authors.forename: W X
authors.initials: WX
authors.lastname: Hu
authors.forename: Z Y
authors.initials: ZY
authors.lastname: Yang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D051379:Mice; D013777:Tetrazoles / Q000138:chemical synthesis*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis*
chemical_list: D000970:Antineoplastic Agents; D013777:Tetrazoles; D014508:Urea