2-[(3aS,4R,6R,6aR)-6-(hydroxymethyl)-2,2-dimethyl-4,5,6,6a-tetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]isoindole-1,3-dione | 1208988-90-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 2-[(3aS,4R,6R,6aR)-6-(hydroxymethyl)-2,2-dimethyl-4,5,6,6a-tetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]isoindole-1,3-dione
• CAS: 1208988-90-2
• 化学式: C₁₇H₁₉NO₅
• 分子量: 317.342
• InChiKey: RPYDZVPDSKNUKO-JXJLXUTGSA-N

物化性质

• 沸点：
  462.8±35.0 °C(Predicted)
• 密度：
  1.331±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  76.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-[(3aS,4R,6R,6aR)-6-(hydroxymethyl)-2,2-dimethyl-4,5,6,6a-tetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]isoindole-1,3-dione 在 盐酸 、 copper(l) iodide 、 四(三苯基膦)钯 、 2,2,6,6-四甲基哌啶氧化物 、 碘苯二乙酸 、 caesium carbonate 、 一水合肼 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 56.5h， 生成 (1S,2R,3S,5R)-3-(1-hydroxy-1-methyl-ethyl)-5-[[2-(2-methoxyethylamino)-6-methyl-5-(4-methylthiazolo[4,5-c]pyridin-2-yl)pyrimidin-4-yl]amino]cyclopentane-1,2-diol
  参考文献：
  名称：

  Synthesis and SAR of geminal substitutions at the C5′ carbosugar position of pyrimidine-derived HCV inhibitors

  摘要：

  The installation of geminal substitution at the C5' position of the carbosugar in our pyrimidine-derived hepatitis C inhibitor series is reported. SAR studies around the C5' position led to the installation of the dimethyl group as the optimal functionality. An improved route was subsequently designed to access these substitutions. Expanded SAR at the C2 amino position led to the utilization of C2 ethers. These compounds exhibited good potency, high selectivity, and excellent plasma exposure and bioavailability in rodent as well as in higher species. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.08.111
• 作为产物：
  描述：

  [(3aS,4R,6R,6aR)-4-(1,3-dioxoisoindol-2-yl)-2,2-dimethyl-4,5,6,6a-tetrahydro-3aH-cyclopenta[d][1,3]dioxol-6-yl]methyl methanesulfonate 在 sodium iodide 作用下， 以 丙酮 为溶剂， 反应 2.0h， 生成 2-[(3aS,4R,6R,6aR)-6-(hydroxymethyl)-2,2-dimethyl-4,5,6,6a-tetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]isoindole-1,3-dione
  参考文献：
  名称：

  Substituted pyridine and pyrimidine derivatives and their use in treating viral infections

  摘要：

  本发明提供了式(I)的化合物：以及所述化合物的互变异构体、异构体和酯，以及所述化合物的药学上可接受的盐、溶剂化合物和前药，其中R、R1、X、Y、Z、R2、R3、R4、R5、R6、R7、R8、R9、R18、R19和n中的每个都是独立选择并如本文所定义。还提供了包含这些化合物的组合物。本发明的化合物作为HCV的抑制剂是有效的，并且在治疗或预防病毒感染和与病毒相关的疾病或紊乱方面，单独或与其他治疗剂一起使用是有用的。

  公开号：

  US09433621B2

文献信息

• [EN] SUBSTITUTED PYRIDINE AND PYRIMIDINE DERIVATIVES AND THEIR USE IN TREATING VIRAL INFECTIONS<br/>[FR] DÉRIVÉS DE PYRIDINE ET PYRIMIDINE SUBSTITUÉES ET LEUR UTILISATION DANS LE TRAITEMENT D'INFECTIONS VIRALES
  申请人：SCHERING CORP

  公开号：WO2010022121A1

  公开（公告）日：2010-02-25

  The present invention provides compounds of Formula (I): and tautomers, isomers, and esters of said compounds, and pharmaceutically acceptable salts, solvates, and prodrugs of said compounds, wherein wherein each of R, R1, X, Y, Z, R2, R3, R4, R5, R6, R7, R8, R9, R18, R19 and n is selected independently and as defined herein. Compositions comprising such compounds are also provided. The compounds of the invention are effective as inhibitors of HCV, and are useful, alone and together with other therapeutic agents, in treating or preventing diseases or disorders such as viral infections and virus-related disorders.

  本发明提供了式(I)的化合物：以及所述化合物的互变异构体、同分异构体和酯，以及所述化合物的药学上可接受的盐、溶剂化合物和前药，其中R、R1、X、Y、Z、R2、R3、R4、R5、R6、R7、R8、R9、R18、R19和n中的每个均独立选择并如本文所定义。还提供了包含这些化合物的组合物。本发明的化合物作为HCV的抑制剂是有效的，并且在治疗或预防病毒感染和与病毒相关的疾病或紊乱方面，单独或与其他治疗剂一起使用是有用的。
• A notable conversion of a thiolacetate to its corresponding sulfonyl chloride
  作者：Yuhua Huang、Frank Bennett、Vishal Verma、F. George Njoroge、Malcolm MacCoss

  DOI：10.1016/j.tetlet.2012.03.111

  日期：2012.6

  A direct conversion of a thiolacetate to its corresponding sulfonyl chloride in the presence of acid and base sensitive functional groups is described.

  描述了在酸和碱敏感的官能团存在下硫羟乙酸盐直接转化为其相应的磺酰氯的方法。
• Construction of a chiral quaternary carbon center by a radical cyclization/ring-enlargement reaction: synthesis of 4α-azidoethyl carbocyclic ribose, a key unit for the synthesis of cyclic ADP-ribose derivatives of biological importance
  作者：Takatoshi Sato、Takayoshi Tsuzuki、Satoshi Takano、Kohtaro Kato、Hayato Fukuda、Mitsuhiro Arisawa、Satoshi Shuto

  DOI：10.1016/j.tet.2015.05.084

  日期：2015.8

  As a stable analog of the second messenger cyclic ADP-ribose (cADPR), we designed 4″-azidoethyl-cyclic ADP-carbocylic-ribose (N3-cADPcR). For the synthesis of N3-cADPcR, 1β-amino-2,3-O-isoproplylidene-4α-azidoethyl carbocyclic-ribose (4) having a chiral quaternary stereogenic center is required as the key unit. We successfully synthesized the desired unit 4 via construction of the quaternary stereogenic

  作为第二信使环ADP-核糖（cADPR）的稳定类似物，我们设计了4''-叠氮基乙基环ADP-碳氢核糖（N 3 -cADPcR）。为了合成N 3 -cADPcR，需要具有手性季立体中心的1β-氨基-2,3- O-异亚丙基-4α-叠氮基碳环核糖（4）作为关键单元。我们通过以硅系链的基团为基础的自由基环化/扩环反应，通过四级立体异构中心的构建成功地合成了所需的单元4。
• SUBSTITUTED PYRIMIDINE DERIVATIVES AND THEIR USE IN TREATING VIRAL INFECTIONS
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP2536410B1

  公开（公告）日：2015-09-23
• SUBSTITUTED PYRIDINE AND PYRIMIDINE DERIVATIVES AND THEIR USE IN TREATING VIRAL INFECTIONS
  申请人：Arasappan Ashok

  公开号：US20110318305A1

  公开（公告）日：2011-12-29

  The present invention provides compounds of Formula (I): and tautomers, isomers, and esters of said compounds, and pharmaceutically acceptable salts, solvates, and prodrugs of said compounds, wherein each of R, R 1 , X, Y, Z, R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 18 , R 19 and n is selected independently and as defined herein. Compositions comprising such compounds are also provided. The compounds of the invention are effective as inhibitors of HCV, and are useful, alone and together with other therapeutic agents, in treating or preventing diseases or disorders such as viral infections and virus-related disorders.