title: Synthesis and antitumor activity of 3-methyl-4-oxo-3,4-dihydroimidazo [5,1-d][1,2,3,5]tetrazine-8-carboxylates and -carboxamides.
abstract: Seventeen novel 3-methyl-4-oxo-3,4-dihydroimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxylate and -carboxamide derivatives were synthesized and evaluated for their growth inhibition in seven human solid tumor and a human leukemia HL-60 cell lines. Compound IVa showed more activity than the other compounds and the positive control temozolomide. In the presence of 40 μg/mL of IVa, the survival rate of all tested tumor cells was less than 10%. Esters displayed more potent antitumour activity than amides and temozolomide against HL-60 cells. These compounds also exhibited considerably enhanced water-solubility.
authors.affiliation: Key Laboratory of Structure-Based Drugs Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Yang
authors.forename: Jie
authors.initials: J
authors.lastname: Cheng
authors.forename: Lin-Xiang
authors.initials: LX
authors.lastname: Zhao
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D018922:HL-60 Cells; D006574:Heterocyclic Compounds, 2-Ring / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D012995:Solubility; D000077204:Temozolomide; D014867:Water / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D006574:Heterocyclic Compounds, 2-Ring; D014867:Water; D003606:Dacarbazine; D000077204:Temozolomide