The synthesis of 4-amino-1-beta-D-ribofuranosylpyrrolo[2,3-d]pyridazin-7 (6H)-one (3) from the reaction of ethyl 3-cyano-1-beta-D-ribofuranosylpyrrole-2-carboxylate (10) and hydrazine is described. The 5:6 pyrrolo[2,3-d]pyridazin-7(6H)-one structure of 3 was established via a three-step conversion of 3 into 1-beta-D-ribofuranosylpyrrolo[2,3-d]pyridazin-4,7(5H,6H)- dio ne (14). 4-Amino-3-chloro-1-beta-D-ribofuranosylpyrrolo[2,3-d]pyridazin+ ++-7(6H)-one (16) 4-amino-3-bromo-1-beta-D-ribofuranosylpyrrolo[2,3-d]pyridazin++ +-7(6H)-one (18) were prepared via N-chlorosuccinimide or N-bromosuccinimide treatment of 4-amino-1-(2,3,5-tri-O-benzyl-beta- D-ribofuranosyl)pyrrolo[2,3-d]pyridazin-7(6H)-one (7) followed by a removal of the benzyl groups with boron trichloride. Direct treatment of 3 with N-iodosuccinimide furnished 4-amino-3-iodo-1-beta-D-ribofuranosylpyrrolo[2,3-d]pyridazin -7(6H)-one (19). The antiproliferative activity of the compounds was determined in L1210, H. Ep. 2 and several additional human tumor cell lines. In L1210 cells, the 3-halo-substituted compounds 16, 18, and 19 exhibited significant cytotoxicity (IC50 = 0.2, 0.1, 0.08 microM, respectively), in contrast to the 3-unsubstituted compound 3, which had only slight activity. The greater antiproliferative activity of 18 and 19 in contrast to 3 was confirmed in H. Ep. 2 cells and KB cells. The antiviral evaluation of these compounds revealed that compounds 16, 18, and 19 were active against human cytomegalovirus in both plaque- and yield-reduction assays. However, this activity was only partially separated from cytotoxicity in human cell lines.

中文翻译：

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4-氨基-1-（β-D-呋喃呋喃糖基）吡咯并[2,3-d]哒嗪-7（6H）-one及其相关衍生物的合成，抗增殖和抗病毒活性。

3-乙基氰基-1-β-D-呋喃呋喃糖基吡咯-2的反应合成4-氨基-1-β-D-呋喃呋喃糖基吡咯并[2,3-d]哒嗪-7（6H）-一（3）。描述了-羧酸盐（10）和肼。5：6吡咯并[2,3-d]哒嗪-7（6H）-1的结构是通过将3转化为1-beta-D-核呋喃核糖基吡咯并[2,3-d]哒嗪-的三步反应建立的4,7（5H，6H）-二烯（14）。4-氨基-3-氯-1-β-D-呋喃核糖基吡咯并[2,3-d]哒嗪+ ++-7（6H）-一（16）4-氨基-3-溴-1-β-D-核呋喃糖基吡咯并[2,3-d] pyridazin ++ + -7（6H）-one（18）是通过N-氯代琥珀酰亚胺或N-溴代琥珀酰亚胺处理4-氨基-1-（2,3,5-三-O-苄基- β-D-呋喃核糖基）吡咯并[2,3-d]哒嗪-7（6H）-一（7），然后用三氯化硼除去苄基。用N-碘代琥珀酰亚胺直接处理的3提供的4-amino-3-iodo-1-beta-D-rifurfuranosylpyrrolo [2,3-d] pyridazin -7（6H）-one（19）。该化合物的抗增殖活性在L1210，H.Ep。2和其他几种人类肿瘤细胞系。在L1210细胞中，3-卤代化合物16、18和19表现出显着的细胞毒性（IC50分别为0.2、0.1、0.08 microM），而3-3-取代的化合物3的活性很小。在H.Ep.中确认了18和19与3相比具有更大的抗增殖活性。2个单元格和KB单元格。这些化合物的抗病毒评估表明，化合物16、18和19在噬菌斑减少和产量减少试验中均具有抗人巨细胞病毒的活性。然而，