(2R,3R,4S,5R)-4-fluoro-2-(hydroxymethyl)-5-(6-methoxy-9H-purin-9-yl)tetrahydrofuran-3-ol

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: (2R,3R,4S,5R)-4-fluoro-2-(hydroxymethyl)-5-(6-methoxy-9H-purin-9-yl)tetrahydrofuran-3-ol
• 英文别名: (2R,3R,4S,5R)-4-fluoro-2-(hydroxymethyl)-5-(6-methoxypurin-9-yl)oxolan-3-ol
• 化学式: C₁₁H₁₃FN₄O₄
• 分子量: 284.247
• InChiKey: BQLCZDLJTPAFTK-WCGPTHBMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  103
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (2R,3R,4S,5R)-4-fluoro-2-(hydroxymethyl)-5-(6-methoxy-9H-purin-9-yl)tetrahydrofuran-3-ol 在 10 % platinum on carbon 氧气 、 碳酸氢钠 、 盐酸 作用下， 以 水 为溶剂， 生成 (2S,3R,4S,5R)-4-fluoro-3-hydroxy-5-(6-methoxy-9H-purin-9-yl)tetrahydrofuran-2-carboxylic acid
  参考文献：
  名称：

  [EN] SALTS OF HIV INHIBITOR COMPOUNDS
  [FR] SELS DE COMPOSÉS INHIBITEURS DU VIH

  摘要：

  这项发明涉及抗病毒化合物的盐、含有这种盐的组合物，以及包括给予这种盐的治疗方法，还涉及用于制备这种盐的过程和中间体。

  公开号：

  WO2010005986A1
• 作为产物：
  描述：

  (3S,4R,5R)-5-((benzoyloxy)methyl)-3-fluorotetrahydrofuran-2,4-diyl dibenzoate 在 氢溴酸 、 sodium hydride 、 potassium carbonate 、 溶剂黄146 作用下， 以 二氯甲烷 、 乙腈 、 mineral oil 为溶剂， 反应 48.0h， 生成 (2R,3R,4S,5R)-4-fluoro-2-(hydroxymethyl)-5-(6-methoxy-9H-purin-9-yl)tetrahydrofuran-3-ol
  参考文献：
  名称：

  [EN] METHODS OF TREATING MEDICAL CONDITIONS AND INHIBITING LINE1 REVERSE TRANSCRIPTASE USING A SUBSTITUTED 4-FLUORO-2,5-DIHYDROFURANYL PHOSPHONIC ACID OR RELATED COMPOUND
  [FR] MÉTHODES DE TRAITEMENT D'ÉTATS MÉDICAUX ET D'INHIBITION DE LA TRANSCRIPTASE INVERSE DE LA LINE1 À L'AIDE D'UN ACIDE 4-FLUORO-2,5-DIHYDROFURANYLE PHOSPHONIQUE SUBSTITUÉ OU D'UN COMPOSÉ APPARENTÉ

  摘要：

  The invention provides methods and compositions for treating medical disorders, such as cancer, and inhibiting LINE1 reverse transcriptase and/or HERV-K reverse transcriptase using a substituted 4-fluoro-2,5-dihydrofuranyl phosphonic acid or related compound.

  公开号：

  WO2022245814A1

文献信息

• Deoxyfluoronucleoside process
  申请人：Bristol-Myers Squibb Company

  公开号：EP0428109A2

  公开（公告）日：1991-05-22

  There is disclosed a process for synthesizing 2′-­fluoro-2′,3′-dideoxyarabinofuranose derivatives of inosine and adenine on a large scale which involves coupling of a fluorosugar derivative and a purine reactant to provide a purine nucleoside intermediate which is then deoxygenated. 6-Chloro or 6-benzamidopurine and 1,3,5-tri-O-benzoyl-2-­deoxy-2-fluoroarabinofuranose are used as starting materials.

  本发明公开了一种大规模合成肌苷和腺嘌呤的 2′-氟-2′,3′-二脱氧阿拉伯呋喃糖衍生物的工艺，该工艺包括将一种氟糖衍生物和一种嘌呤反应物偶联，以提供一种嘌呤核苷中间体，然后将其脱氧。6-Cloro 或 6-benzamidopurine 和 1,3,5-tri-O-benzoyl-2-de-deoxy-2-fluoroarabinofuranose 可用作起始原料。
• Discovery of GS-9131: Design, synthesis and optimization of amidate prodrugs of the novel nucleoside phosphonate HIV reverse transcriptase (RT) inhibitor GS-9148
  作者：Richard L. Mackman、Adrian S. Ray、Hon C. Hui、Lijun Zhang、Gabriel Birkus、Constantine G. Boojamra、Manoj C. Desai、Janet L. Douglas、Ying Gao、Deborah Grant、Genevieve Laflamme、Kuei-Ying Lin、David Y. Markevitch、Ruchika Mishra、Martin McDermott、Rowchanak Pakdaman、Oleg V. Petrakovsky、Jennifer E. Vela、Tomas Cihlar

  DOI：10.1016/j.bmc.2010.03.041

  日期：2010.5

  GS-9148 [(5-(6-amino-purin-9-yl)-4-fluoro-2,5-dihydro-furan-2-yloxymethyl)phosphonic acid] 4 is a novel nucleoside phosphonate HIV-1 reverse transcriptase (RT) inhibitor with a unique resistance profile toward N(t)RTI resistance mutations. To effectively deliver 4 and its active phosphorylated metabolite 15 into target cells, a series of amidate prodrugs were designed as substrates of cathepsin A, an intracellular lysosomal carboxypeptidase highly expressed in peripheral blood mononuclear cells (PBMCs). The ethylalaninyl phosphonamidate prodrug 5 (GS-9131) demonstrated favorable cathepsin A substrate properties, in addition to favorable in vitro intestinal and hepatic stabilities. Following oral dosing (3 mg/kg) in Beagle dogs, high levels (>9.0 mu M) of active metabolite 15 were observed in PBMCs, validating the prodrug design process and leading to the nomination of 5 as a clinical candidate. (C) 2010 Elsevier Ltd. All rights reserved.
• Antiviral compounds
  申请人：THE WELLCOME FOUNDATION LIMITED

  公开号：EP0417999B1

  公开（公告）日：1996-03-13
• 2-Fluoro-arabinofuranosyl purine nucleosides
  申请人：Sloan-Kettering Institute For Cancer Research

  公开号：EP0219829B1

  公开（公告）日：1992-12-30
• US5420115A
  申请人：——

  公开号：US5420115A

  公开（公告）日：1995-05-30