Study For The Synthesis And Biological Activity Of The Mo Acetazolamide Derivatives

Temozolomide is one of the new imidazoletetrazine compounds,which has good antitumour active to brain glioma,leukemia,melanoma,lymphoma and solid tumor. Many research workers have synthesized many temozolomide derivatives which were substituted in 3-,4-,6- and 8-,and the testing of biological activity indicated that 8-substituted amide derivatives of temozolomide had better antitumour active.On the base of the characteristics of temozolomide and its derivatives, 5-diazoimidazole-4-carboxamide was prepared from 5-aminoimidazole-4-carboxa mide through diazotization reaction,methyl isocyanate was prepared from methyl carbamyl chloride by elimination reaction,the two intermediates was stirred at room temperature and temozolomide was gotten.General yield was increased to 69.69% from 65.66%under the optimum reaction condition.In order to inhencing the fat-soluble we could introduce aryl in 8- of temozolomide.Temozolomide was carboxylated and acyl chloridized,then reacted with aryl amines and obtained fourteen N-substituted-3-methyl-imidazol[5,1 -d][1,2,3,5]tetrazine-8-carboxamide derivatives,three bis-temozolomide aryl derivatives and three bis-temozolomide acyclic derivatives were synthsized as control study,all of them have never been reported in literature.The structure of final products were characterized correcttly by elemental analysis,IR,¹H-NMR,and ¹³C-NMR,the structure and spectral data of TD-2 were elucidated in details in the paper.Preliminary studies on inhibitory activity of temozolomide derivatives against prostatic neoplasms(PC3) showed that TD-5, TD-6,TD-9,TD-10 and TD-20 had certain antitumor actives to PC3 at 1μM and TD-7,TD-8,TD-11,TD-13,TD-19 had certain antitumor actives to PC3 at 10μM.