6-chloro-2-methylthiopurin-9-ylmethyl-2,2-dimethylpropionate | 793695-95-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 6-chloro-2-methylthiopurin-9-ylmethyl-2,2-dimethylpropionate
• 英文别名: 6-chloro-2-methylthiopurin-9-ylmethyl 2,2-dimethylpropionate；(6-chloro-2-methylsulfanylpurin-9-yl)methyl 2,2-dimethylpropanoate
• CAS: 793695-95-1
• 化学式: C₁₂H₁₅ClN₄O₂S
• 分子量: 314.796
• InChiKey: UFILOIUTGBIMFE-UHFFFAOYSA-N

物化性质

• 沸点：
  486.3±55.0 °C(Predicted)
• 密度：
  1.41±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  95.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6-chloro-2-methylthiopurin-9-ylmethyl-2,2-dimethylpropionate 在 sodium hydroxide 、 水 、 异丙醇 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 以56%的产率得到6-氯-2-甲硫基-7H-嘌呤
  参考文献：
  名称：

  [EN] PURINE DERIVATIVES AS A3 AND A1 ADENOSINE RECEPTOR AGONISTS
  [FR] DERIVES DE PURINE COMME AGONISTES DU RECEPTEUR D'ADENOSINE A3 ET A1

  摘要：

  揭示了一种公式为[N-甲烷卡巴腺嘌呤核苷]的高效A3腺苷受体激动剂，包括这种核苷的制药组合物，以及这些核苷的使用方法，其中R1-R6如规范中所定义。这些核苷被考虑用于治疗多种疾病，例如炎症、心肌缺血、中风、哮喘、糖尿病和心律失常。该发明还提供了既是A1受体又是A3受体激动剂的化合物，用于心脏保护。

  公开号：

  WO2006031505A1
• 作为产物：
  描述：

  二甲基二硫 、 2-amino-6-chloropurin-9-yl-methyl 2,2-dimethylpropionate 在 亚硝酸特丁酯 作用下， 以 乙腈 为溶剂， 以44.5 %的产率得到6-chloro-2-methylthiopurin-9-ylmethyl-2,2-dimethylpropionate
  参考文献：
  名称：

  [EN] A CYCLIN-DEPENDENT KINASE INHIBITOR
  [FR] INHIBITEUR DE KINASE DÉPENDANTE DE LA CYCLINE

  摘要：

  提供了一系列具有很强的抑制周期素依赖性激酶（CDK）活性的化合物或其药用可接受的盐。同时也提供了相应的组合物。

  公开号：

  WO2022206795A1

文献信息

• Purine Derivatives as A3 and A1 Adenosine Receptor Agonists
  申请人：Jacobson A. Kenneth

  公开号：US20070232626A1

  公开（公告）日：2007-10-04

  Disclosed are (N)-methanocarba adenine nucleosides of the formula: [Formula] as highly potent A 3 adenosine receptor agonists, pharmaceutical compositions comprising such nucleosides, and a method of use of these nucleosides, wherein R 1 -R 6 are as defined in the specification. These nucleosides are contemplated for use in the treatment a number of diseases, for example, inflammation, cardiac ischemia, stroke, asthma, diabetes, and cardiac arrhythmias. The invention also provides compounds that are agonists of both A 1 and A 3 adenosine receptors for use in cardioprotection.

  本发明公开了一种(N)-甲烷卡巴腺嘌呤核苷，其化学式为：[Formula]，作为高效的A3腺苷受体激动剂，包括这种核苷的制药组合物和使用这些核苷的方法，其中R1-R6如规范中所定义。这些核苷可用于治疗多种疾病，例如炎症，心脏缺血，中风，哮喘，糖尿病和心律失常。本发明还提供了既是A1受体激动剂又是A3受体激动剂的化合物，用于心脏保护。
• Purine derivatives as A3 and A1 adenosine receptor agonists
  申请人：The United States of America as represented by the Department of Health and Human Services

  公开号：US07825126B2

  公开（公告）日：2010-11-02

  Disclosed are (N)-methanocarba adenine nucleosides of the formula: as highly potent A3 adenosine receptor agonists, pharmaceutical compositions comprising such nucleosides, and a method of use of these nucleosides, wherein R1-R6 are as defined in the specification. These nucleosides are contemplated for use in the treatment a number of diseases, for example, inflammation, cardiac ischemia, stroke, asthma, diabetes, and cardiac arrhythmias. The invention also provides compounds that are agonists of both A1 and A3 adenosine receptors for use in cardioprotection.

  本发明涉及一种公式为(N)-methanocarba腺嘌呤核苷的化合物，其具有高效的A3腺苷受体激动剂作用，包括这些核苷的制药组合物和使用这些核苷的方法，其中R1-R6如规范所定义。这些核苷可用于治疗多种疾病，例如炎症、心脏缺血、中风、哮喘、糖尿病和心律失常。本发明还提供了既是A1受体又是A3受体激动剂的化合物，用于心脏保护。
• (<i>N</i>)-Methanocarba 2,<i>N</i>⁶-Disubstituted Adenine Nucleosides as Highly Potent and Selective A₃ Adenosine Receptor Agonists
  作者：Susanna Tchilibon、Bhalchandra V. Joshi、Soo-Kyung Kim、Heng T. Duong、Zhan-Guo Gao、Kenneth A. Jacobson

  DOI：10.1021/jm049580r

  日期：2005.3.1

  A series of ring-constrained (N)-methanocarba-5 '-uronamide 2,N-6-disubstituted adenine nucleosides have been synthesized via Mitsunobu condensation of the nucleobase precursor with a pseudosugar ring containing a 5 '-ester functionality. Following appropriate functionalization of the adenine ring, the ester group was converted to the 5 '-N-methylamide. The compounds, mainly 2-chloro-substituted derivatives, were tested in both binding and functional assays at human adenosine receptors (ARs), and many were found to be highly potent and selective A(3)AR agonists. Selected compounds were compared in binding to the rat A(3)AR to assess their viability for testing in rat disease models. The N-6-(3-chlorobenzyl) and N-6-(3-bromobenzyl) analogues displayed K-i values at the human A(3)AR of 0.29 and 0.38 nM, respectively. Other subnanomolar affinities were observed for the following N-6 derivatives: 2,5-dichlorobenzyl, 5-iodo-2-methoxybenzyl, trans-2-phenyl-1-cyclopropyl, and 2,2-diphenylethyl. Selectivity for the human A3AR in comparison to the A(3)AR was the following (fold): the N-6-(2,2-diphenylethyl) analogue 34 (1900), the N-6-(2,5-dimethoxybenzyl) analogue 26 (1200), the N-6-(2,5-dichlorobenzyl) and N-6-(2-phenyl-1-cyclopropyl) analogues 20 and 33 (1000), and the N-6-(3-substituted benzyl) analogues 17, 18, 28, and 29 (700-900). Typically, even greater selectivity ratios were obtained in comparison with the A(2A) and A(2B)ARs. The (N)-methanocarba-5 '-uronamide analogues were full agonists at the A(3)AR, as indicated by the inhibition of forskolin-stimluated adenylate cyclase at a concentration of 10 mu M. The N-6-(2,2-diphenylethyl) derivative was an A(3)AR agonist in the (N)-methanocarba-5 '-uronamide series, although it was an antagonist in the ribose series. Thus, many of the previously known groups that enhance A(3)AR affinity in the 9-riboside series, including those that reduce intrinsic efficacy, may be adapted to the (N)-methanocarba nucleoside series of full agonists.
• PURINE DERIVATIVES AS A3 AND A1 ADENOSINE RECEPTOR AGONISTS
  申请人：The Government of the United States of America, as repres. by the Secretary of Health and Human Services, Nat. Inst. of Health

  公开号：EP1794162A1

  公开（公告）日：2007-06-13
• US7825126B2
  申请人：——

  公开号：US7825126B2

  公开（公告）日：2010-11-02