5-amino-3-(5'-O-tert-butyl-dimethylsilanyl-β-D-ribofuranosyl)-3H-thiazolo[4,5-d]pyrimidin-2-one

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-amino-3-(5'-O-tert-butyl-dimethylsilanyl-β-D-ribofuranosyl)-3H-thiazolo[4,5-d]pyrimidin-2-one
• 英文别名: 5-Amino-3-(5'-o-tert-butyl-dimethylsilanyl-beta-d-ribofuranosyl)-3h-thiazolo[4,5-d]pyrimidin-2-one；5-amino-3-[(2R,3R,4S,5R)-5-[[tert-butyl(dimethyl)silyl]oxymethyl]-3,4-dihydroxyoxolan-2-yl]-[1,3]thiazolo[4,5-d]pyrimidin-2-one
• 化学式: C₁₆H₂₆N₄O₅SSi
• 分子量: 414.558
• InChiKey: VTXKDEUZXBCXIH-UORFTKCHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.08
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  156
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  5-amino-3-(5'-O-tert-butyl-dimethylsilanyl-β-D-ribofuranosyl)-3H-thiazolo[4,5-d]pyrimidin-2-one 在 氢氟酸 、 三乙胺 作用下， 以 四氢呋喃 、 吡啶 、 乙腈 为溶剂， 反应 26.0h， 生成 (2R,3R,4R,5R)-2-(hydroxymethyl)-5-(5-amino-2-oxothiazolo[4,5-d]pyrimidin-3(2H)-yl)tetrahydrofuran-3,4-diyl diacetate
  参考文献：
  名称：

  [EN] 3-beta-D-RIBOFURANOSYLTHIAZOLO[4,5-d]PYRIDIMINE NUCLEOSIDES AND USES THEREOF
  [FR] NUCLEOSIDES 3-20051222WO03045968A1ANADYS PHARMACEUTICALS INC [US]20030605WX1-20XUS5041426AROBINS ROLAND K [US], et al19910820compounds 6,7,41,42X1,2,12XWO03045968A1ANADYS PHARMACEUTICALS INC [US]20030605"Remington's Pharmaceutical Sciences"Remington's Pharmaceutical SciencesBARANOV ET AL., CHEM. HET. COMPOUNDS, vol. 11, 1975, pages 73BARANOV ET AL.CHEM. HET. COMPOUNDS19751173

  摘要：

  本发明涉及3-ß-D-核糖呋喃噻唑[4,5-d]吡啶嘧啶核苷和含有此类化合物的药物组合物，具有免疫调节活性。本发明还涉及这类化合物和组合物的治疗或预防用途，以及通过给予这类化合物的有效剂量来治疗本文所述的疾病和疾病的方法。

  公开号：

  WO2005121162A1
• 作为产物：
  描述：

  7-thia-8-oxoguanosine 在 咪唑 、 4-二甲氨基吡啶 、 氯化亚砜 、 potassium carbonate 、 溶剂黄146 、 锌 作用下， 以 甲醇 、 DMF (N,N-dimethylformamide) 、 氯仿 、 乙腈 为溶剂， 反应 78.0h， 生成 5-amino-3-(5'-O-tert-butyl-dimethylsilanyl-β-D-ribofuranosyl)-3H-thiazolo[4,5-d]pyrimidin-2-one
  参考文献：
  名称：

  [EN] 3-beta-D-RIBOFURANOSYLTHIAZOLO[4,5-d]PYRIDIMINE NUCLEOSIDES AND USES THEREOF
  [FR] NUCLEOSIDES 3-20051222WO03045968A1ANADYS PHARMACEUTICALS INC [US]20030605WX1-20XUS5041426AROBINS ROLAND K [US], et al19910820compounds 6,7,41,42X1,2,12XWO03045968A1ANADYS PHARMACEUTICALS INC [US]20030605"Remington's Pharmaceutical Sciences"Remington's Pharmaceutical SciencesBARANOV ET AL., CHEM. HET. COMPOUNDS, vol. 11, 1975, pages 73BARANOV ET AL.CHEM. HET. COMPOUNDS19751173

  摘要：

  本发明涉及3-ß-D-核糖呋喃噻唑[4,5-d]吡啶嘧啶核苷和含有此类化合物的药物组合物，具有免疫调节活性。本发明还涉及这类化合物和组合物的治疗或预防用途，以及通过给予这类化合物的有效剂量来治疗本文所述的疾病和疾病的方法。

  公开号：

  WO2005121162A1

文献信息

• Administration of TLR7 ligands and prodrugs thereof for treatment of infection by hepatitis C virus
  申请人：Averett R. Devron

  公开号：US20050054590A1

  公开（公告）日：2005-03-10

  This invention relates to methods for treating or preventing hepatitis C virus infections in mammals using Toll-Like Receptor (TLR)7 ligands and prodrugs thereof. More particularly, this invention relates to methods of orally administering a therapeutically effective amount of one or more prodrugs of TLR7 ligands for the treatment or prevention of hepatitis C viral infection. Oral administration of these TLR7 immunomodulating ligands and prodrugs thereof to a mammal provides therapeutically effective amounts and reduced undesirable side effects.

  这项发明涉及使用Toll样受体（TLR）7配体及其前药治疗或预防哺乳动物体内的丙型肝炎病毒感染的方法。更具体地，这项发明涉及口服给予一种或多种TLR7配体前药的治疗有效量，用于治疗或预防丙型肝炎病毒感染。将这些TLR7免疫调节配体及其前药口服给哺乳动物可提供治疗有效量并减少不良副作用。
• 3-B-D-ribofuranosylthiazolo [4,5-d] pyridimine nucleosides and uses thereof
  申请人：Averett R. Devron

  公开号：US20050070556A1

  公开（公告）日：2005-03-31

  The invention is directed to 3-β-D-ribofuranosylthiazolo[4,5-d]pyridimine nucleosides and pharmaceutical compositions containing such compounds that have immunomodulatory activity. The invention is also directed to the therapeutic or prophylactic use of such compounds and compositions, and to methods of treating diseases and disorders described herein, by administering effective amounts of such compounds.

  这项发明涉及3-β-D-核糖呋喃基噻唑并[4,5-d]吡啶嘧啶核苷及含有这种化合物的具有免疫调节活性的药物组合物。该发明还涉及这种化合物和组合物的治疗或预防用途，以及通过给予这种化合物的有效量来治疗本文描述的疾病和紊乱的方法。
• Discovery of ANA975: An Oral Prodrug of the TLR-7 Agonist Isatoribine
  作者：Alan X. Xiang、Stephen E. Webber、Bradley M. Kerr、Erik J. Rueden、Joseph R. Lennox、Gregory J. Haley、Tingmin Wang、John S. Ng、Mark R. Herbert、David L. Clark、Virginia N. Banh、Wei Li、Simon P. Fletcher、Kevin R. Steffy、Darian M. Bartkowski、Leonid I. Kirkovsky、Lisa A. Bauman、Devron R. Averett

  DOI：10.1080/15257770701490472

  日期：2007.11.26

  5-d]pyrimidin-2-one derivative, was synthesized in the search of an oral prodrug of isatoribine, a small molecule toll-like receptor 7 (TLR-7) agonist. Several strategies were studied to enable the kilogram-scale synthesis of ANA975. Three general total syntheses are described. In the phase I clinical study of ANA975 against hepatitis C virus (HCV), conversion to isatoribine in plasma was rapid and effective, delivering

  ANA975是一种5-氨基-3-β-D-呋喃呋喃糖基-3H-噻唑并[4,5-d]嘧啶-2-一衍生物，其合成是寻找一种小分子收费类似的伊沙托立宾的口服前药受体7（TLR-7）激动剂。研究了几种策略以实现ANA975的公斤级合成。描述了三个一般的总合成。在针对丙型肝炎病毒（HCV）的ANA975的I期临床研究中，血浆中快速转化为isatoribine的效果是提供与临床相关的isatoribine水平。
• 3-Beta-D-Ribofuranosylthiazolo[ 4,5-D] Pyridimine Nucleosides and Uses Thereof
  申请人：Averett Devron R.

  公开号：US20080070852A1

  公开（公告）日：2008-03-20

  The invention is directed to 3-β-D-ribofuranosylthiazolo[4,5-d]pyrimidine nucleosides and pharmaceutical compositions containing such compounds that have immunomodulatory activity. The invention is also directed to the therapeutic or prophylactic use of such compounds and compositions, and to methods of treating diseases and disorders described herein, by administering effective amounts of such compounds.

  本发明涉及3-β-D-核糖呋喃基噻唑[4,5-d]嘧啶核苷及含有这种化合物的药物组合物，其具有免疫调节活性。本发明还涉及使用这种化合物和组合物进行治疗或预防，以及通过给予有效剂量的这种化合物来治疗本文所述的疾病和障碍的方法。
• 3-B-D-RIBOFURANOSYLTHIAZOLO[4,5-d]PYRIMIDINE NUCLEOSIDES AND USES THEREOF
  申请人：Averet Devron R.

  公开号：US20080255063A1

  公开（公告）日：2008-10-16

  The invention is directed to 3-β-D-ribofuranosylthiazolo[4,5-d]pyrimidine nucleosides and pharmaceutical compositions containing such compounds that have immunomodulatory activity. The invention is also directed to the therapeutic or prophylactic use of such compounds and compositions, and to methods of treating diseases and disorders described herein, by administering effective amounts of such compounds.

  本发明涉及3-β-D-核糖呋喃噻唑并[4,5-d]嘧啶核苷及含有这种化合物的制药组合物，该化合物具有免疫调节活性。本发明还涉及使用这种化合物和组合物的治疗或预防用途，以及通过给予有效剂量的这种化合物来治疗本文所述的疾病和障碍的方法。