(2S,3R,4S,5R)-4-fluoro-3-hydroxy-5-(6-methoxy-9H-purin-9-yl)tetrahydrofuran-2-carboxylic acid | 875534-29-5

• 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: (2S,3R,4S,5R)-4-fluoro-3-hydroxy-5-(6-methoxy-9H-purin-9-yl)tetrahydrofuran-2-carboxylic acid
• 英文别名: (2S,3R,4S,5R)-4-fluoro-3-hydroxy-5-(6-methoxypurin-9-yl)oxolane-2-carboxylic acid
• CAS: 875534-29-5
• 化学式: C₁₁H₁₁FN₄O₅
• 分子量: 298.231
• InChiKey: ZKNLWCVIELANPR-SXVXDFOESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.48
• 重原子数：
  21.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  119.59
• 氢给体数：
  2.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  (2S,3R,4S,5R)-4-fluoro-3-hydroxy-5-(6-methoxy-9H-purin-9-yl)tetrahydrofuran-2-carboxylic acid 在 偶氮二甲酸二异丙酯 、 一溴化碘 、 三苯基膦 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 diphenyl [5-(R)-(6-methoxypurin-9-yl)-4-(R)-fluoro-3-(R)-iodo-tetrahydrofuran-2(R)-yloxymethyl]phosphonic acid
  参考文献：
  名称：

  CYCLOPENTENE-OXYMETHYLENE PHOSPHONAMIDATES AND RELATED COMPOUNDS AND THEIR USE IN TREATING MEDICAL CONDITIONS

  摘要：

  Substituted cyclopentene-oxymethylene phosphonamidates and related compounds, pharmaceutical compositions, their use for inhibiting LINE1 reverse transcriptase and/or HERV- K reverse transcriptase activity, and their use in the treatment of medical disorders, such as cancer, are disclosed herein.

  公开号：

  WO2024107859A1
• 作为产物：
  描述：

  (3S,4R,5R)-5-((benzoyloxy)methyl)-3-fluorotetrahydrofuran-2,4-diyl dibenzoate 在 Jones reagent 、 氢溴酸 、 silica gel 、 sodium hydride 、 potassium carbonate 、 溶剂黄146 作用下， 以 二氯甲烷 、 丙酮 、 乙腈 、 mineral oil 为溶剂， 反应 68.0h， 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] 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

• [EN] SALTS OF HIV INHIBITOR COMPOUNDS<br/>[FR] SELS DE COMPOSÉS INHIBITEURS DU VIH
  申请人：GILEAD SCIENCES INC

  公开号：WO2010005986A1

  公开（公告）日：2010-01-14

  The invention is related to salts of anti-viral compounds, compositions containing such salts, and therapeutic methods that include the administration of such salts, as well as to processes and intermediates useful for preparing such salts.

  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。
• 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.