1-((6a′R,8′R,9a′S)-2′,2′,4′,4′-tetraisopropyltetrahydrospiro[cyclopropane-1,9′-furo[3,2-f ][1,3,5,2,4]trioxadisilocin]-8′-yl)pyrimidine-2,4(1H,3H)-dione | 140902-00-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 1-((6a′R,8′R,9a′S)-2′,2′,4′,4′-tetraisopropyltetrahydrospiro[cyclopropane-1,9′-furo[3,2-f ][1,3,5,2,4]trioxadisilocin]-8′-yl)pyrimidine-2,4(1H,3H)-dione
• 英文别名: 1-((6a'R,8'R,9a'S)-2',2',4',4'-tetraisopropylhexahydrospiro[cyclopropane-1,9'-furo[3,2-f][1,3,5,2,4]trioxadisilocine]-8'-yl)pyrimidine-2,4(1H,3H)-dione；1-[(6aR,8R,9aS)-2,2,4,4-tetra(propan-2-yl)spiro[6,6a,8,9a-tetrahydrofuro[3,2-f][1,3,5,2,4]trioxadisilocine-9,1'-cyclopropane]-8-yl]pyrimidine-2,4-dione
• CAS: 140902-00-7
• 化学式: C₂₃H₄₀N₂O₆Si₂
• 分子量: 496.751
• InChiKey: MVWHOWANWWWTAF-HMXCVIKNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.17
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  86.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-((6a′R,8′R,9a′S)-2′,2′,4′,4′-tetraisopropyltetrahydrospiro[cyclopropane-1,9′-furo[3,2-f ][1,3,5,2,4]trioxadisilocin]-8′-yl)pyrimidine-2,4(1H,3H)-dione 在 吡啶 、 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 1.75h， 生成 1-((4R,6R,7S)-7-hydroxy-6-((4-methoxyphenyl)(diphenyl)methoxymethyl)-5-oxaspiro[2.4]hept-4-yl)-1H-pyrimidin-2,4(1H,3H)-dione
  参考文献：
  名称：

  Cyclopropyl polymerase inhibitors

  摘要：

  公开号：

  EP2141172B1
• 作为产物：
  描述：

  3-benzoyl-1-((6aR,8R,9aS)-2,2,4,4-tetraisopropyl-4',5',6,6a,8,9a-hexahydrospiro[furo[3,2-f][1,3,5,2,4]-trioxadisilocine-9,3'-pyrazole]-8-yl)pyrimidine-2,4(1H,3H)-dione 在 二苯甲酮 、 氨 作用下， 以 甲醇 、 二氯甲烷 、 乙腈 、 苯 为溶剂， 反应 1.0h， 生成 1-((6a′R,8′R,9a′S)-2′,2′,4′,4′-tetraisopropyltetrahydrospiro[cyclopropane-1,9′-furo[3,2-f ][1,3,5,2,4]trioxadisilocin]-8′-yl)pyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  Cyclopropyl polymerase inhibitors

  摘要：

  公开号：

  EP2141172B1

文献信息

• [EN] URACYL CYCLOPROPYL NUCLEOTIDES<br/>[FR] NUCLÉOTIDES DE TYPE URACYLCYCLOPROPYLE
  申请人：CENTOCOR ORTHO BIOTECH PRODUCT

  公开号：WO2010066699A1

  公开（公告）日：2010-06-17

  Compounds of the formula (I) including any possible stereoisomers thereof, wherein: R1 is hydrogen or halo; R4 is a monophosphate, diphosphate or triphosphate ester; or R4 is a group of formula (II) R7 is optionally substituted phenyl; naphthyl; indolyl or N-C1-C6alkyloxycarbonyl- indolyl; R8 is hydrogen, C1-C6alkyl, benzyl; R8' is hydrogen, C1-C6alkyl, benzyl; or R8 and R8' together with the carbon atom to which they are attached form C3-C7cycloalkyl; R9 is C1-C10alkyl, benzyl, or optionally substituted phenyl; or a pharmaceutically acceptable salt or solvate thereof. pharmaceutical formulations and the use of compounds I as HCV inhibitors.

  化合物的公式(I)，包括其任何可能的立体异构体，其中：R1是氢或卤素；R4是单磷酸酯、二磷酸酯或三磷酸酯；或者R4是公式(II)的基团，其中R7是可选取代的苯基；萘基；吲哚基或N-C1-C6烷氧羰基-吲哚基；R8是氢、C1-C6烷基、苄基；R8'是氢、C1-C6烷基、苄基；或者R8和R8'与它们所连接的碳原子形成C3-C7环烷基；R9是C1-C10烷基、苄基或可选取代的苯基；或其药学上可接受的盐或溶剂。制药配方和化合物I作为HCV抑制剂的用途。
• Preparation of 2′-Deoxy-2′-spirocyclopropylcytidine via an Alternative Cyclopropanation Reaction
  作者：Sébastien Lemaire、Coura Diène、Andrei Gavryushin、Xavier Mollat Du Jourdin、Léa Paolini、Xavier Jusseau、Paul Knochel、Vittorio Farina

  DOI：10.1021/acs.joc.8b02784

  日期：2019.4.19

  Herein we report the preparation of 2′-deoxy-2′-spirocyclopropylcytidine via an alternative cyclopropanation reaction starting from γ-silyl tertiary alcohols. Activation of the hydroxyl function with thionyl chloride in the presence of 4-DMAP allows the ring-closing step under mild conditions. Participation of the uracil moiety in the cyclization step is proposed.

  在本文中，我们报道了从γ-甲硅烷基叔醇开始的另一种环丙烷化反应，制备了2'-脱氧-2'-螺环丙基胞嘧啶核苷。在4-DMAP存在下用亚硫酰氯活化羟基官能团允许在温和条件下进行闭环步骤。提出了尿嘧啶部分参与环化步骤。
• 2′-Deoxy-2′-spirocyclopropylcytidine Revisited: A New and Selective Inhibitor of the Hepatitis C Virus NS5B Polymerase
  作者：Tim H. M. Jonckers、Tse-I Lin、Christophe Buyck、Sophie Lachau-Durand、Koen Vandyck、Steven Van Hoof、Leen A. M. Vandekerckhove、Lili Hu、Jan Martin Berke、Leen Vijgen、Lieve L. A. Dillen、Maxwell D. Cummings、Herman de Kock、Magnus Nilsson、Christian Sund、Christina Rydegård、Bertil Samuelsson、Åsa Rosenquist、Gregory Fanning、Kristof Van Emelen、Kenneth Simmen、Pierre Raboisson

  DOI：10.1021/jm101050a

  日期：2010.11.25

  The current therapy for hepatitis C virus (HCV) infection has limited efficacy, in particular against the genotype 1 virus, and a range of side effects. In this context of high unmet medical need, more efficacious drugs targeting HCV nonstructural proteins are of interest. Here we describe 2'-deoxy-2'-spirocyclo-propylcytidine (5) as a new inhibitor of the HCV NS5B RNA-dependent RNA polymerase, displaying an EC50 of 7.3 mu M measured in the Huh7-Rep cell line and no associated cytotoxicity (CC50 > 98.4 mu M). Computational results indicated high similarity between 5 and related HCV inhibiting nucleosides. A convenient synthesis was devised, facilitating synthesis of multigram quantities of 5. As the exposure measured after oral administration of 5 was found to be limited, the 3'-mono- and 3',5'-diisobutyryl ester prodrugs 20 and 23, respectively, were evaluated, The oral dosing of 23 led to substantially increased exposure to 5 in both rats and dogs.
• Nucleic acid and related compounds. 75. Synthesis and radical-induced ring-opening reactions of 2'-deoxyadenosine-2'-spirocyclopropane and its uridine analogs. Mechanistic probes for ribonucleotide reductases
  作者：Vicente Samano、Morris J. Robins

  DOI：10.1021/ja00036a077

  日期：1992.5
• Cyclopropyl polymerase inhibitors
  申请人：Janssen Products, L.P.

  公开号：EP2141172B1

  公开（公告）日：2012-10-24