methyl 1-(β-D-2',3',5'-tri-O-benzoylribofuranosyl)-4-iodo-pyrazole-3-carboxylate | 138786-93-3

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物
• 英文名称: methyl 1-(β-D-2',3',5'-tri-O-benzoylribofuranosyl)-4-iodo-pyrazole-3-carboxylate
• 英文别名: methyl 4-iodo-1-(2',3',5'-tribenzoyl-β-D-ribofuranosyl)pyrazole-3-carboxylate；methyl 1-[(2R,3R,4R,5R)-3,4-dibenzoyloxy-5-(benzoyloxymethyl)oxolan-2-yl]-4-iodopyrazole-3-carboxylate
• CAS: 138786-93-3
• 化学式: C₃₁H₂₅IN₂O₉
• 分子量: 696.452
• InChiKey: JBHFANYLABSGCF-MIRJVGOZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.48
• 重原子数：
  43.0
• 可旋转键数：
  9.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  132.25
• 氢给体数：
  0.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  methyl 1-(β-D-2',3',5'-tri-O-benzoylribofuranosyl)-4-iodo-pyrazole-3-carboxylate 在 sodium hydroxide 、 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 6.0h， 生成 4-iodo-1-β-D-ribofuranosylpyrazole-3-carboxylic acid
  参考文献：
  名称：

  Manfredini, Stefano; Bazzanini, Rita; Baraldi, Pier Giovanni, Medicinal Chemistry Research, 1996, vol. 6, # 5, p. 293 - 311

  摘要：

  DOI：
• 作为产物：
  描述：

  甲基4-碘-1H-吡唑-3-羧酸酯 在 三甲基氯硅烷 、 三氟甲磺酸三甲基硅酯 、 对甲苯磺酸 、 六甲基二硅氮烷 作用下， 以 乙腈 为溶剂， 反应 4.0h， 生成 methyl 1-(β-D-2',3',5'-tri-O-benzoylribofuranosyl)-4-iodo-pyrazole-3-carboxylate
  参考文献：
  名称：

  A new direct glycosylation of pyrimidine, pyrazole, imidazole and purine heterocycles via their N-tetrahydropyranyl (THP) derivatives

  摘要：

  嘧啶、哌唑、咪唑和嘌呤N-四氢吡喃基（THP）衍生物在一锅反应中以区域和立体选择性方式转化为相应的β-D-2′,3′,5′-三-O-苯甲酰核糖苷衍生物，反应中使用了1-β-乙酰-2′,3′,5′-三-O-苯甲酰核糖、六甲基二硅氮烷（HMDS）、三甲基氯硅烷（TMSCI）和三甲基硅烷三氟甲磺酸盐（TMST）。

  DOI：

  10.1039/c39940000583

文献信息

• Pyrazole-related nucleosides. Synthesis and antiviral/antitumor activity of some substituted pyrazole and pyrazolo[4,3-d]-1,2,3-triazin-4-one nucleosides
  作者：Stefano Manfredini、Rita Bazzanini、Pier Giovanni Baraldi、Mario Guarneri、Daniele Simoni、Maria E. Marongiu、Alessandra Pani、Paolo La Colla、Enzo Tramontano

  DOI：10.1021/jm00083a017

  日期：1992.3

  preparation, diazotization, and in situ cyclization of opportune pyrazole glycosides 9 and 10 was required. Moreover derivatives having the general formula 5 were considered not only as synthetic intermediates in the synthesis of 3 but also as carbon bioisosteres of ribavirin 4. All compounds were evaluated in vitro for cytostatic and antiviral activity. The pyrazolo[4,3-d]-1,2,3-triazin-4-one nucleosides that

  制备了几种吡唑和吡唑并[4,3-d] -1,2,3-三嗪-4-一核糖核苷，并测试了其抗病毒/抗肿瘤活性。通过标准方法制备适当的杂环碱。吡唑6a-e，g，i和吡唑并[4,3-d] -1,2,3-三嗪-4-酮12f-1的糖基化反应，是通过六甲基二硅氮烷与1-β-O-乙酰基-甲硅烷基化作用介导的2,3,5-三-O-苯甲酰基-D-呋喃呋喃糖的相应糖苷7a-e，g，8g，i，13f，h，k和14f的收率很高，但不能应用于化合物12g ，i，j，l。为了克服这种情况，需要一种不同的策略，涉及适当的吡唑糖苷9和10的制备，重氮化和原位环化。此外，具有通式5的衍生物不仅被认为是3的合成中的合成中间体，而且还被认为是利巴韦林4的碳生物等排体。在体外对所有化合物进行了细胞抑制和抗病毒活性的评价。所产生的吡唑并[4，3-d] -1,2,3-三嗪-4-酮核苷基本上没有任何活性。仅15h，k显示出对T细胞的中等细胞
• Design, synthesis and antiproliferative activity of methyl 4-Iodo-1-β-D-ribofuranosyl-pyrazole-3-carboxylate and related compounds
  作者：Stefano Manfredini、Rita Bazzanini、Pier Giovanni Baraldi、Daniele Simoni、Silvia Vertuani、Alessandra Pani、Elisabetta Pinna、Franca Scintu、Donatella Lichino、Paolo La Colla

  DOI：10.1016/0960-894x(96)00216-8

  日期：1996.6

  In a SAR study on azole-related nucleosides we have designed some pyrazole-nucleoside analogs characterised, for the first time, by a carboxylic ester moiety. 4-Iodo-1-beta-D-ribofuranosyl-pyrazole-3-carboxylate showed a wide spectrum of antiproliferative activity and a particularly low cytotoxicity against resting PBL, being, unlike the other azole nucleosides, more active than the corresponding primary amide. Copyright (C) 1996 Elsevier Science Ltd
• Effects of Introduction of Hydrophobic Group on Ribavirin Base on Mutation Induction and Anti-RNA Viral Activity
  作者：Kei Moriyama、Tetsuya Suzuki、Kazuo Negishi、Jason D. Graci、Corinne N. Thompson、Craig E. Cameron、Masahiko Watanabe

  DOI：10.1021/jm7009952

  日期：2008.1.1

  One of the possible mechanisms of antiviral action of ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide, 1) is the accumulation of mutations in viral genomic RNA. The ambiguous incorporation of 5'-triphosphate of ribavirin (RTP, 8) by a viral RNA-dependent RNA polymerase (RdRp) is a key step of the mutation induction. We synthesized three ribavirin analogues that possess hydrophobic groups, 4-iodo-1- 1-beta-D-ribofuranosylpyrazole-3-carboxamide (7a), 4-propynyl-1-beta-D-ribofuranosylpyrazole-3-carboxamide (7b), and 4-phenylethynyl-1-beta-D-ribofuranosylpyrazole-3-carboxamide (7c), and the corresponding triphosphates (9a, 9b, and 9c, respectively). Steady-state kinetics analysis of the incorporation of these triphosphate analogues by a poliovirus RdRp, 3D(pol), revealed that while the incorporation efficiency of 9a was comparable to RTP, 9b and 9c showed lower efficiency than RTP. Antipolioviral activity of 7a and 7b was much more moderate than ribavirin, and 7c showed no antipolioviral activity. Effects of substituting groups on the incorporation efficiency by 3D(pol) and a strategy for a rational design of more active ribavirin analogues are discussed.