5'-amino-N(6),N(6)-bis(tert-butoxycarbonyl)-5'-deoxy-2',3'-O-isopropylideneadenosine | 1192228-09-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 5'-amino-N(6),N(6)-bis(tert-butoxycarbonyl)-5'-deoxy-2',3'-O-isopropylideneadenosine
• 英文别名: 5'- amino-N⁶,N⁶-bis(tert-butoxycarbonyl)-5'-deoxy-2',3'-O-isopropylideneadenosine
• CAS: 1192228-09-3
• 化学式: C₂₃H₃₄N₆O₇
• 分子量: 506.559
• InChiKey: XDHBFMPGLIXCFY-SCFUHWHPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.88
• 重原子数：
  36.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  153.15
• 氢给体数：
  1.0
• 氢受体数：
  12.0

反应信息

• 作为反应物：
  描述：

  5'-amino-N(6),N(6)-bis(tert-butoxycarbonyl)-5'-deoxy-2',3'-O-isopropylideneadenosine 、 N-(苄氧基羰基)磺酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以6.94 g的产率得到5'-[(N-benzyloxycarbonyl)sulfamoylamino]-N(6),N(6)-bis(tert-butoxycarbonyl)-5'-deoxy-2',3'-O-isopropylideneadenosine
  参考文献：
  名称：

  A critical electrostatic interaction mediates inhibitor recognition by human asparagine synthetase

  摘要：

  The first sulfoximine-based inhibitor of human asparagine synthetase (ASNS) with nanomolar potency has been shown to suppress proliferation of asparaginase-resistant MOLT-4 cells in the presence of L-asparaginase. This validates literature hypotheses concerning the viability of human ASNS as a target for new drugs against acute lymphoblastic leukemia and ovarian cancer. Developing structure-function relationships for this class of human ASNS inhibitors has proven diffcult, however, primarily because of the absence of rapid synthetic procedures for constructing highly functionalized sulfoximines. We now report conditions for the efficient preparation of these compounds by coupling sulfoxides and sulfamides in the presence of a rhodium catalyst. Access to this methodology has permitted the construction of two new adenylated sulfoximines, which were expected to exhibit similar binding affinity and better bioavailability than the original human ASNS inhibitor. Steady-state kinetic characterization of these compounds, however, has revealed the importance of a localized negative charge on the inhibitor that mimics that of the phosphate group in a key acyl-adenylate reaction intermediate. These experiments place an important constraint on the design of sulfoximine libraries for screening experiments to obtain ASNS inhibitors with increased potency and bioavailability. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.07.071
• 作为产物：
  描述：

  5'-azido-5'-deoxy-2',3'-O-isopropylidene adenosine 在 4-二甲氨基吡啶 、 palladium 10% on activated carbon 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 1.5h， 生成 5'-amino-N(6),N(6)-bis(tert-butoxycarbonyl)-5'-deoxy-2',3'-O-isopropylideneadenosine
  参考文献：
  名称：

  [EN] NOVEL HISTONE METHYLTRANSFERASE INHIBITORS
  [FR] NOUVEAUX INHIBITEURS D'HISTONE MÉTHYLTRANSFÉRASES

  摘要：

  本发明涉及式(I)定义的新的化合物。这些化合物是七-β-链家族组蛋白甲基转移酶的抑制剂，特别是KMT9的抑制剂。

  公开号：

  WO2021053158A1

文献信息

• Dinucleosides with Non-Natural Backbones: A New Class of Ribonuclease A and Angiogenin Inhibitors
  作者：Joy Debnath、Swagata Dasgupta、Tanmaya Pathak

  DOI：10.1002/chem.201102816

  日期：2012.2.6

  Ribonuclease A (RNase A) serves as a convenient model enzyme in the identification and development of inhibitors of proteins that are members of the ribonuclease superfamily. This is principally because the biological activity of these proteins, such as angiogenin, is linked to their catalytic ribonucleolytic activity. In an attempt to inhibit the biological activity of angiogenin, which involves new

  核糖核酸酶A（RNase A）在鉴定和开发作为核糖核酸酶超家族成员的蛋白质的抑制剂中，是一种方便的模型酶。这主要是因为这些蛋白质（例如血管生成素）的生物学活性与它们的催化核糖核酸分解活性有关。为了抑制涉及新血管形成的血管生成素的生物活性，我们采用了具有不同非天然骨架的不同二核苷。这些化合物是通过将氨基核苷与二元羧酸偶联以及将氨基和羧基核苷与氨基酸偶联而合成的。这些分子表现出竞争抑制作用，其抑制常数（K i）值为（59±3）和（155±5）μM还发现该化合物与相应的K i以竞争方式抑制血管生成素值在微摩尔范围内。发现与二核苷主链连接的另一个极性基团的存在是造成与两种蛋白质紧密结合的原因。由于在两个核苷部分之间掺入了非天然骨架，因此发现了不同的核糖核酸水解亚位点的特异性发生了变化。尽管磷酸酯基团被非天然接头取代，但发现这些分子与血管生成素的核糖核酸裂解位点残基选择性相互作用，而细胞结合位点和核