(1'R,4'S)-9-[4-(hydroxymethyl)cyclopent-2-en-1-yl]adenine | 147332-45-4

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: (1'R,4'S)-9-[4-(hydroxymethyl)cyclopent-2-en-1-yl]adenine
• 英文别名: (-)-(1'R,4'S)-9-[4-(hydroxymethyl)cyclopent-2-enyl]adenine；[(1S,4R)-4-(6-amino-9H-purin-9-yl)cyclopent-2-enyl]methanol；(1′R,4′S)-9-[4′-(hydroxymethyl)cyclopent-2′-en-1′-yl]adenine；(1α,4α)-4-(6-Amino-9H-purin-9-yl)-2-cyclopentenylcarbinol；9-[(1'R,4'S)-4-(Hydroxymethyl)-2-cyclopenten-1-yl]adenine；((1s,4r)-4-(6-Amino-9h-purin-9-yl)cyclopent-2-enyl)methanol；[(1S,4R)-4-(6-aminopurin-9-yl)cyclopent-2-en-1-yl]methanol
• CAS: 147332-45-4
• 化学式: C₁₁H₁₃N₅O
• 分子量: 231.257
• InChiKey: COZAZKCWQGBJDE-SFYZADRCSA-N

物化性质

• 熔点：
  183-185 °C(Solv: chloroform (67-66-3); methanol (67-56-1))
• 沸点：
  516.9±60.0 °C(Predicted)
• 密度：
  1.61±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  89.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (1'R,4'S)-9-[4-(hydroxymethyl)cyclopent-2-en-1-yl]adenine 在 sodium hydride 、 氨基磺酰氯 作用下， 以 乙二醇二甲醚 为溶剂， 反应 16.5h， 以55%的产率得到(1'R,4'S)-9-[4-((sulfamoyl)oxymethyl)cyclopent-2-en-1-yl]adenine
  参考文献：
  名称：

  Antitubercular Nucleosides That Inhibit Siderophore Biosynthesis:  SAR of the Glycosyl Domain

  摘要：

  Tuberculosis is the leading cause of infectious disease mortality in the world by a bacterial pathogen. We previously demonstrated that a bisubstrate inhibitor of the adenylation enzyme MbtA, which is responsible for the second step of mycobactin biosynthesis, exhibited potent antitubercular activity. Here we systematically investigate the structure-activity relationships of the bisubstrate inhibitor glycosyl domain resulting in the identification of a carbocyclic analogue that possesses a K-I(app) value of 2.3 nM and MIC99 values of 1.56 mu M against M. tuberculosis H37Rv. The SAR data suggest the intriguing possibility that the bisubstrate inhibitors utilize a transporter for entry across the mycobacterial cell envelope. Additionally, we report improved conditions for the expression of MbtA and biochemical analysis, demonstrating that MbtA follows a random sequential enzyme mechanism for the adenylation half-reaction.

  DOI：

  10.1021/jm061068d
• 作为产物：
  描述：

  (1R,4S)-4-[(1S,2S)-1,2-bis[[tert-butyl(dimethyl)silyl]oxy]-2-[(1S,4R)-4-hydroxycyclopent-2-en-1-yl]ethyl]cyclopent-2-en-1-ol 在 吡啶 、 4-二甲氨基吡啶 、 tris(dibenzylideneacetone)dipalladium(0) chloroform complex 、 sodium tetrahydroborate 、 sodium periodate 、 三异丙基亚磷酸酯 、 四丁基氟化铵 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二甲基亚砜 为溶剂， 反应 8.0h， 生成 (1'R,4'S)-9-[4-(hydroxymethyl)cyclopent-2-en-1-yl]adenine
  参考文献：
  名称：

  A New Synthetic Route to Nucleosides:  Dissymmetric Construction of a Cyclopentene System by Double [3,3]-Sigmatropic Rearrangement and Double Ring-Closing Metathesis

  摘要：

  [GRAPHICS]The dissymmetric synthesis of a carbocyclic nucleoside was achieved by a novel double [3,3]-sigmatropic rearrangement/double ring-closing metathesis strategy with a high stereoselectivity.

  DOI：

  10.1021/ol040006j

文献信息

• Bisubstrate Inhibitors for the Enzyme Catechol O-Methyltransferase (COMT): Dramatic Effects of Ribose Modifications on Binding Affinity and Binding Mode
  作者：Christian Lerner、Romain Siegrist、Eliane Schweizer、François Diederich、Volker Gramlich、Roland Jakob-Roetne、Gerhard Zürcher、Edilio Borroni

  DOI：10.1002/hlca.200390093

  日期：2003.4

  Inhibition of the enzyme catechol O-methyltransferase (COMT) is of significant interest in the therapy of Parkinson's disease. Described herein are structural analogs of the potent bisubstrate inhibitor (−)-1 (IC50=9 nM; Table 1) for COMT, with target modifications of the central ribose moiety. Their synthesis involves, as key intermediates, adenosine derivatives, which are transformed to the potential

  抑制儿茶酚O-甲基转移酶（COMT）在帕金森氏病的治疗中具有重大意义。本文描述了用于COMT的强效双底物抑制剂（-）- 1（IC 50 = 9 nM;表1）的结构类似物，具有中心核糖部分的目标修饰。其合成包括，关键中间体，腺苷衍生物，其由六个步骤：（a类似序列转化到电势双底物抑制剂方案1 - 4）。将化合物进行酶促测定以测定其体外通过动力学测量分析了对COMT的抑制活性，以及​​对辅因子S-腺苷甲硫氨酸（SAM）的结合侧的抑制机理（图3）。结合亲和力和结合模式都对核糖部分的修饰极其敏感（表1）。从（-）- 1变为（-）- 2（IC 50 = 28μM）后2'-OH基团的去除导致结合亲和力下降超过三个数量级。同时，相对于SAM结合位点保持竞争抑制动力学，从而支持双底物结合模式。与（−）- 2不同，双脱氧核糖抑制剂（-）- 3（IC 50 = 3μM）表现出混合，而环戊烷衍生物（+）- 4（IC
• Antibacterial Agents
  申请人：Aldrich Courtney

  公开号：US20080293666A1

  公开（公告）日：2008-11-27

  The invention provides compounds of formula (I) and salts thereof: R 1 -L-R 2 —B wherein R 1 , L, R 2 , and B have any of the values defined herein, as well as compositions comprising such compounds, and therapeutic methods comprising the administration of such compounds or salts. The compounds block siderophore production in bacteria and are useful as antibacterial agents.

  这项发明提供了化合物的公式(I)及其盐：R1-L-R2—B，其中R1、L、R2和B具有本文中定义的任何值，以及包含这种化合物的组合物，以及包含这种化合物或盐的治疗方法。这些化合物可以阻断细菌中的铁载体产生，并可用作抗菌剂。
• Application of Phosphoramidate ProTide Technology Significantly Improves Antiviral Potency of Carbocyclic Adenosine Derivatives
  作者：Christopher McGuigan、Alshaimaa Hassan-Abdallah、Sheila Srinivasan、Yikang Wang、Adam Siddiqui、Susan M. Daluge、Kristjan S. Gudmundsson、Huiqiang Zhou、Ed W. McLean、Jennifer P. Peckham、Thimysta C. Burnette、Harry Marr、Richard Hazen、Lynn D. Condreay、Lance Johnson、Jan Balzarini

  DOI：10.1021/jm060776w

  日期：2006.11.30

  phosphoramidate pronucleotide (ProTide) technology to the antiviral agent carbocyclic L-d4A (L-Cd4A). The phenyl methyl alaninyl parent ProTide of L-Cd4A was prepared by Grignard-mediated phosphorochloridate reaction and resulted in a compound with significantly improved anti-HIV (2600-fold) and HBV activity. We describe modifications of the aryl, ester, and amino acid regions of the ProTide and how these changes

  我们报告了氨基磷酸酯原核苷酸（ProTide）技术在抗病毒剂碳环L-d4A（L-Cd4A）中的应用。L-Cd4A的苯基甲基丙氨酸基母体ProTide是通过格利雅（Grignard）介导的磷酰氯反应制备的，得到的化合物具有显着改善的抗HIV（2600倍）和HBV活性。我们描述了ProTide的芳基，酯和氨基酸区域的修饰，以及这些变化如何影响抗病毒活性和代谢稳定性。注意到针对HIV和HBV的SAR分别且不同。另外，由D-核苷D-Cd4A和双脱氧类似物L-CddA和D-CddA制备ProTide。与母体药物相比，这些化合物显示出更适度的效能改善。综上所述，当将ProTide方法应用于L-Cd4A时，在体外的效价提高了9000倍，非常成功，抗HIV的能力提高了。为了临床前候选人的选择，我们使用食蟹猴肝脏和肠道S9馏分进行了代谢稳定性研究。
• Dideoxycarbocyclic nucleosides
  申请人：Regents of the University of Minnesota

  公开号：US04916224A1

  公开（公告）日：1990-04-10

  Antiviral and antitumor compounds are disclosed of general formula: ##STR1## wherein Z is H, OH or NH.sub.2, Y is CH or N, the bond indicated by C.sub.1 '--C.sub.2 ' is absent or, in combination with the C.sub.1 '--C.sub.2 ' bond is the unit CH.dbd.CH, and X is selected from the group consisting of H, N(R.sub.2), SR, OR or halogen, wherein R is H, lower (C.sub.1 -C.sub.4)alkyl, aryl or mixtures thereof, and the pharmaceutically acceptable salts thereof.

  抗病毒和抗肿瘤化合物的一般公式为：##STR1## 其中 Z 为 H、OH 或 NH2，Y 为 CH 或 N，由 C1'--C2' 指示的键缺失或者与 C1'--C2' 键组合为 CH.dbd.CH 单元，X 选自 H、N(R2)、SR、OR 或卤素的组，其中 R 为 H、较低的（C1-C4）烷基、芳基或它们的混合物，以及其药用盐。
• STABILIZED NUCLEOTIDES FOR MEDICAL TREATMENT
  申请人：Deshpande Milind

  公开号：US20160016986A1

  公开（公告）日：2016-01-21

  5′-Deuterated nucleosides and nucleotides and modifications thereof are provided for use in medical therapies, including as antiviral, anti-tumor and anti-neoplastic agents. In one embodiment, compounds, methods and uses are provided for the treatment of hepatitis C, RSV, HSV and other viral diseases in a host, including a human.

  提供了用于医疗疗法的5'-氘代核苷和核苷酸以及其修饰，包括作为抗病毒、抗肿瘤和抗肿瘤剂。在一个实施例中，提供了化合物、方法和用途，用于治疗丙型肝炎、RSV、HSV和其他病毒性疾病在宿主中，包括人类。