Goddard A J, Orr R M, Stock J A, Wilman D E
Drug Development Section, Institute of Cancer Research, Sutton, Surrey, UK.
Anticancer Drug Des. 1987 Dec;2(3):235-45.
A series of derivatives of the ribonucleotide reductase inhibitory anti-tumour agent 2,3-dihydro-1H-imidazo[1,2-b]pyrazole (IMPY), including all the methyl analogues, have been synthesised. IMPY itself caused 50% inhibition of L1210 tumour-derived ribonucleotide reductase at a concentration of 0.39 mM, comparable with enzyme obtained from other sources. The analogues proved to be no better than IMPY, either as inhibitors of this enzyme or of the growth of L1210 cells in vitro. No correlation was apparent between biological activity and position of substitution.
已合成了一系列核糖核苷酸还原酶抑制性抗肿瘤药物2,3-二氢-1H-咪唑并[1,2-b]吡唑（IMPY）的衍生物，包括所有甲基类似物。IMPY本身在浓度为0.39 mM时可使L1210肿瘤来源的核糖核苷酸还原酶抑制50%，这与从其他来源获得的酶相当。这些类似物作为该酶的抑制剂或对L1210细胞体外生长的抑制效果并不比IMPY更好。生物活性与取代位置之间没有明显的相关性。
