6-氯-9-(2-C-甲基-beta-D-呋喃核糖基)-9H-嘌呤 | 205171-05-7

• 物质功能分类: 有机原料 - 杂环化合物
• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 中文名称: 6-氯-9-(2-C-甲基-beta-D-呋喃核糖基)-9H-嘌呤
• 英文名称: 6-chloro-9-(2-C-methyl-β-D-ribofuranosyl)-9H-purine
• 英文别名: 6-chloro-9H-(2-C-methyl-β-D-ribofuranosyl)purine；(2R,3R,4R,5R)-2-(6-Chloro-9H-purin-9-yl)-5-(hydroxymethyl)-3-methyltetrahydrofuran-3,4-diol；(2R,3R,4R,5R)-2-(6-chloropurin-9-yl)-5-(hydroxymethyl)-3-methyloxolane-3,4-diol
• CAS: 205171-05-7
• 化学式: C₁₁H₁₃ClN₄O₄
• 分子量: 300.702
• InChiKey: MOMRKSMRPOKFCN-YRKGHMEHSA-N

物化性质

• 沸点：
  590.1±60.0 °C(Predicted)
• 密度：
  1.86

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  114
• 氢给体数：
  3
• 氢受体数：
  7

安全信息

• 危险性防范说明：
  P264,P280,P302+P352,P337+P313,P305+P351+P338,P362+P364,P332+P313
• 危险性描述：
  H315,H319
• 储存条件：
  温度：2-8°C，存储时应使用惰性气体。

反应信息

• 作为反应物：
  描述：

  6-氯-9-(2-C-甲基-beta-D-呋喃核糖基)-9H-嘌呤 在 chromium(VI) oxide 、 氯化亚砜 、 硫酸 、 对甲苯磺酸 、 三乙胺 、 原甲酸三乙酯 作用下， 以 丙酮 、 乙腈 为溶剂， 反应 101.0h， 生成 (3aR,4S,6R,6aR)-6-[6-(3-Iodo-benzylamino)-purin-9-yl]-2,2,6a-trimethyl-tetrahydro-furo[3,4-d][1,3]dioxole-4-carboxylic acid ethyl ester
  参考文献：
  名称：

  2‘-C-Methyl Analogues of Selective Adenosine Receptor Agonists:  Synthesis and Binding Studies

  摘要：

  2'-C-Methyl analogues of selective adenosine receptor agonists such as (R)-PIA, CPA, CCPA, NECA, and IB-MECA were synthesized in order to further investigate the subdomain that binds the ribose moiety. Binding affinities of these new compounds at A(1) and A(2A) receptors in bovine brain membranes and at A(3) in rat testis membranes were determined and compared. It was found that the 2'-C-methyl modification resulted in a decrease of the affinity, particularly at A(2A) and A(3) receptors. When such modification was combined with N-6-substitutions with groups which induce high potency and selectivity at Al receptors, the high affinity was retained and the selectivity was increased. Thus, 2-chloro-2'-C-methyl-N-6-cyclopentyladenosine (2'-Me-CCPA), which displayed a K-i value of 1.8 nM at A(1) receptors, was selective for A(1) vs A(2A) and A(3) receptors by 2166- and 2777-fold, respectively, resulting in one of the most potent and A(1)-selective agonists so far known. In functional assay, this compound inhibited forskolin-stimulated adenylyl cyclase activity with an IC50 value of 13.1 nM, acting as a full agonist.

  DOI：

  10.1021/jm9707737
• 作为产物：
  描述：

  1,2,3,5-四苯甲酰氧基-2-C-甲基-beta-D-呋喃核糖 在 三氟甲磺酸三甲基硅酯 、 氨 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 乙腈 为溶剂， 反应 11.0h， 生成 6-氯-9-(2-C-甲基-beta-D-呋喃核糖基)-9H-嘌呤
  参考文献：
  名称：

  2‘-C-Methyl Analogues of Selective Adenosine Receptor Agonists:  Synthesis and Binding Studies

  摘要：

  2'-C-Methyl analogues of selective adenosine receptor agonists such as (R)-PIA, CPA, CCPA, NECA, and IB-MECA were synthesized in order to further investigate the subdomain that binds the ribose moiety. Binding affinities of these new compounds at A(1) and A(2A) receptors in bovine brain membranes and at A(3) in rat testis membranes were determined and compared. It was found that the 2'-C-methyl modification resulted in a decrease of the affinity, particularly at A(2A) and A(3) receptors. When such modification was combined with N-6-substitutions with groups which induce high potency and selectivity at Al receptors, the high affinity was retained and the selectivity was increased. Thus, 2-chloro-2'-C-methyl-N-6-cyclopentyladenosine (2'-Me-CCPA), which displayed a K-i value of 1.8 nM at A(1) receptors, was selective for A(1) vs A(2A) and A(3) receptors by 2166- and 2777-fold, respectively, resulting in one of the most potent and A(1)-selective agonists so far known. In functional assay, this compound inhibited forskolin-stimulated adenylyl cyclase activity with an IC50 value of 13.1 nM, acting as a full agonist.

  DOI：

  10.1021/jm9707737

文献信息

• Structure−Activity Relationship of Purine Ribonucleosides for Inhibition of Hepatitis C Virus RNA-Dependent RNA Polymerase
  作者：Anne B. Eldrup、Charles R. Allerson、C. Frank Bennett、Sanjib Bera、Balkrishen Bhat、Neelima Bhat、Michele R. Bosserman、Jennifer Brooks、Christine Burlein、Steven S. Carroll、P. Dan Cook、Krista L. Getty、Malcolm MacCoss、Daniel R. McMasters、David B. Olsen、Thazha P. Prakash、Marija Prhavc、Quanlai Song、Joanne E. Tomassini、Jie Xia

  DOI：10.1021/jm030424e

  日期：2004.4.1

  to identify inhibitors of hepatitis C viral (HCV) replication, we report here the synthesis and evaluation of a series of nucleoside analogues and their corresponding triphosphates. Nucleosides were evaluated for their ability to inhibit HCV RNA replication in a cell-based, subgenomic replicon system, while nucleoside triphosphates were evaluated for their ability to inhibit in vitro RNA synthesis mediated

  作为识别丙型肝炎病毒 (HCV) 复制抑制剂的持续努力的一部分，我们在此报告了一系列核苷类似物及其相应的三磷酸盐的合成和评估。评估了核苷在基于细胞的亚基因组复制子系统中抑制 HCV RNA 复制的能力，而评估了核苷三磷酸抑制由 HCV RNA 依赖性 RNA 聚合酶 NS5B 介导的体外 RNA 合成的能力。2'-C-甲基腺苷和 2'-C-甲基鸟苷被确定为 HCV RNA 复制的有效抑制剂，并且发现相应的三磷酸盐是 HCV NS5B 介导的 RNA 合成的有效抑制剂。在基于细胞的测定中产生的数据证明了围绕活性核苷的相当严格的构效关系。发现 C2 上超过甲基的空间体积增加、甲基取代基的立体化学或区域化学的变化，或杂碱的特性变化超过内源性腺嘌呤或鸟嘌呤的变化，会导致抑制活性的丧失。结果突出了核糖构型 2'-和 3'-羟基药效团在基于细胞的测定中抑制 HCV RNA 复制的重要性，并证明包含 2
• Nucleoside derivatives for treating hepatitis C virus infection
  申请人：Genelabs Technologies, Inc.

  公开号：US20040147464A1

  公开（公告）日：2004-07-29

  Disclosed are compounds, compositions and methods for treating hepatitis C virus infections.

  本文揭示了用于治疗丙型肝炎病毒感染的化合物、组合物和方法。
• Compounds and Pharmaceutical Compositions for the Treatment of Viral Infections
  申请人：SOMMADOSSI Jean-Pierre

  公开号：US20090238790A2

  公开（公告）日：2009-09-24

  Provided herein are compounds, compositions and methods for the treatment of liver disorder, including HCV and/or HBV infections. Specifically, compound and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents.

  本文提供了用于治疗肝脏疾病，包括HCV和/或HBV感染的化合物、组合物和方法。具体来说，披露了核苷衍生物的化合物和组合物，可以单独或与其他抗病毒药物联合使用。
• NUCLEOSIDE DERIVATIVES FOR TREATING HEPATITIS C VIRUS INFECTION
  申请人：Roberts Christopher Don

  公开号：US20080249060A1

  公开（公告）日：2008-10-09

  Disclosed are compounds, compositions and methods for treating hepatitis C virus infections.

  本发明涉及用于治疗丙型肝炎病毒感染的化合物、组合物和方法。
• Compounds and pharmaceutical compositions for the treatment of viral infections
  申请人：Sommadossi Jean-Pierre

  公开号：US20080286230A1

  公开（公告）日：2008-11-20

  Provided herein are compounds, compositions and methods for the treatment of liver disorder, including HCV and/or HBV infections. Specifically, compound and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents.

  本文提供了用于治疗肝脏疾病，包括HCV和/或HBV感染的化合物、组合物和方法。具体地，本文公开了核苷衍生物的化合物和组合物，可以单独或与其他抗病毒药物联合使用。