(3R,4R,5R)-5-(2-acetoxyethyl)tetrahydrofuran-2,3,4-triyl triacetate | 828937-35-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (3R,4R,5R)-5-(2-acetoxyethyl)tetrahydrofuran-2,3,4-triyl triacetate
• 英文别名: 2-[(2R,3R,4R)-3,4,5-triacetyloxyoxolan-2-yl]ethyl acetate
• CAS: 828937-35-5
• 化学式: C₁₄H₂₀O₉
• 分子量: 332.307
• InChiKey: NRNYITKXKITZQC-ZHZAVPAVSA-N

物化性质

• 沸点：
  392.7±42.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.09
• 重原子数：
  23.0
• 可旋转键数：
  6.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  114.43
• 氢给体数：
  0.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  (3R,4R,5R)-5-(2-acetoxyethyl)tetrahydrofuran-2,3,4-triyl triacetate 在 三甲基氯硅烷 、 三氟甲磺酸三甲基硅酯 、 氨 、 六甲基二硅氮烷 作用下， 以 甲醇 为溶剂， 生成 9-(5-Desoxy-β-D-ribo-hexofuranosyl)adenin
  参考文献：
  名称：

  5′-Homoaristeromycin. Synthesis and antiviral activity against orthopox viruses

  摘要：

  An efficient synthesis of 5'-homoaristeromycin has been developed. This permitted an extensive antiviral analysis, which found potent activity toward vaccinia, cowpox, and monkeypox viruses. For comparative purposes, 5'-homoadenosine was made available by a newly designed route and found to be inactive. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.10.019
• 作为产物：
  描述：

  2-[(3aR,5R,6R,6aR)-6-acetyloxy-2,2-dimethyl-3a,5,6,6a-tetrahydrofuro[2,3-d][1,3]dioxol-5-yl]ethyl acetate 生成 (3R,4R,5R)-5-(2-acetoxyethyl)tetrahydrofuran-2,3,4-triyl triacetate
  参考文献：
  名称：

  SALCINES, ELLEN M.;SCHNELLER, STEWART W., NUCLEOSIDES AND NUCLEOTIDES, 8,(1989) N-6, C. 1083-1084

  摘要：

  DOI：

文献信息

• Orally Bioavailable Small-Molecule CD73 Inhibitor (OP-5244) Reverses Immunosuppression through Blockade of Adenosine Production
  作者：Xiaohui Du、Jared Moore、Brian R. Blank、John Eksterowicz、Dena Sutimantanapi、Natalie Yuen、Todd Metzger、Brenda Chan、Tom Huang、Xi Chen、Yuping Chen、Frank Duong、Wayne Kong、Jae H. Chang、Jessica Sun、Tatiana Zavorotinskaya、Qiuping Ye、Melissa R. Junttila、Chudi Ndubaku、Lori S. Friedman、Valeria R. Fantin、Daqing Sun

  DOI：10.1021/acs.jmedchem.0c01086

  日期：2020.9.24

  The adenosinergic pathway represents an attractive new therapeutic approach in cancer immunotherapy. In this pathway, ecto-5-nucleotidase CD73 has the unique function of regulating production of immunosuppressive adenosine (ADO) through the hydrolysis of AMP. CD73 is overexpressed in many cancers, resulting in elevated levels of ADO that correspond to poor patient prognosis. Therefore, reducing the level of ADO via inhibition of CD73 is a potential strategy for treating cancers. Based on the binding mode of adenosine 5'-(alpha,beta-methylene)-diphosphate (AOPCP) with human CD73, we designed a series of novel monophosphonate small-molecule CD73 inhibitors. Among them, OP-5244 (35) proved to be a highly potent and orally bioavailable CD73 inhibitor. In preclinical studies, 35 completely inhibited ADO production in both human cancer cells and CD8(+) T cells. Furthermore, 35 lowered the ratio of ADO/AMP significantly and reversed immunosuppression in mouse models, indicating its potential as an in vivo tool compound for further development.