2',3'-O-isopropylidene-N⁶-ethyladenosine | 185848-21-9

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 2',3'-O-isopropylidene-N⁶-ethyladenosine
• 英文别名: ((3aR,4R,6R,6aR)-6-(6-(ethylamino)-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol；N6-ethyl-2',3'-O-isopropylideneadenosine；[(3aR,4R,6R,6aR)-4-[6-(ethylamino)purin-9-yl]-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methanol
• CAS: 185848-21-9
• 化学式: C₁₅H₂₁N₅O₄
• 分子量: 335.363
• InChiKey: YELWFOGDKIKNGH-IDTAVKCVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2',3'-O-isopropylidene-N⁶-ethyladenosine 在 sodium hydride 、 氨基磺酰氯 作用下， 以 四氢呋喃 、 乙二醇二甲醚 为溶剂， 反应 16.5h， 以76%的产率得到N6-ethyl-2',3'-O-isopropylidene-5'-O-(sulfamoyl)adenosine
  参考文献：
  名称：

  用核苷双底物类似物抑制结核分枝杆菌中的铁载体生物合成：5'-O-[N-（水杨酰基）氨磺酰基]腺苷核碱基结构域的构效关系。

  摘要：

  5'-O-[N-(水杨基)氨磺酰基]腺苷 (Sal-AMS) 是一类新型抗结核药物的原型，可抑制参与分枝杆菌素生物合成的称为 MbtA 的芳酸腺苷酸化酶 (AAAE)。在此，我们报告了一系列全面系统的类似物的基于结构的设计、合成、生化和生物学评估，探索了 Sal-AMS 嘌呤核碱基结构域的构效关系。值得注意的是，2-苯基-Sal-AMS 衍生物 26 表现出异常有效的抗结核活性，在 0.049 microM 的缺铁条件下具有 MIC99，而 N-6-环丙基-Sal-AMS 16 导致提高的效力和 64-增强铁缺乏条件下相对于铁充足条件下的活性，与设计的作用机制一致的表型。

  DOI：

  10.1021/jm800567v
• 作为产物：
  描述：

  6-氯嘌呤核苷 在 硫酸 、 三乙胺 作用下， 以 乙醇 为溶剂， 反应 18.5h， 生成 2',3'-O-isopropylidene-N⁶-ethyladenosine
  参考文献：
  名称：

  α,β-Methylene-ADP (AOPCP) Derivatives and Analogues: Development of Potent and Selective ecto-5′-Nucleotidase (CD73) Inhibitors

  摘要：

  ecto-5'-Nucleotidase (eN, CD73) catalyzes the hydrolysis of extracellular AMP to adenosine. eN inhibitors have potential for use as cancer therapeutics. The eN inhibitor alpha,beta-methylene-ADP (AOPCP, adenosine-5'-O-[(phosphonomethyl)phosphonic acid]) was used as a lead structure, and derivatives modified in various positions were prepared. Products were tested at rat recombinant eN. 6-(Ar)alkylamino substitution led to the largest improvement in potency. N-6-Monosubstitution was superior to symmetrical N-6,N-6-disubstitution. The most potent inhibitors were N-6-(4chlorobenzyl)-(10l, PSB-12441, K-i 7.23 n.M), N-6-phenylethyl(10h, PSB-12425, K-i 8.04 nM), and N-6-benzyl-adenosine-5'-O[(phosphonomethyl)phosphonic acid] (10g, PSB-12379, K-i 9.03 nM). Replacement of the 6-NH group in 10g by 0 (10q, PSB-12431) or S (10r, PSB-12553) yielded equally potent inhibitors (10q, 9.20 nM; 10r, 9.50 aM). Selected compounds investigated at the human enzyme did not show species differences; they displayed high selectivity versus other ecto-nudeotidases and ADP-activated P2Y receptors. Moreover, high metabolic stability was observed. These compounds represent the most potent eN inhibitors described to date.

  DOI：

  10.1021/acs.jmedchem.5b00802

文献信息

• Inhibitors of DNA Methyltransferase
  申请人：Wahhab Amal

  公开号：US20080132525A1

  公开（公告）日：2008-06-05

  The invention relates to the inhibition of DNA methyltransferase isoforms DNMT1 and DNMT3b2. The invention provides compounds and methods for inhibiting DNMT1 and DNMT3b2.

  这项发明涉及抑制DNA甲基转移酶亚型DNMT1和DNMT3b2。该发明提供了用于抑制DNMT1和DNMT3b2的化合物和方法。
• Copper-Catalyzed Intramolecular Alkoxylation of Purine Nucleosides: One-Step Synthesis of 5′-<i>O</i>,8-Cyclopurine Nucleosides
  作者：Mingwu Yu、Zhiqian Wang、Junbin Hu、Shunlai Li、Hongguang Du

  DOI：10.1021/acs.joc.5b01360

  日期：2015.10.2

  A novel copper-catalyzed intramolecular dehydrogenative alkoxylation of purine nucleosides has been developed successfully, providing the 5′-O,8-cyclopurine nucleosides in one-step with a yield up to 90%. The method, which utilized an inexpensive CuCl catalyst and a di-tert-butyl peroxide (DTBP) oxidant was suitable in a broad substrate scope and proceeded well even in gram scale.

  已成功开发了一种新型的铜催化的嘌呤核苷分子内脱氢烷氧基化反应，一步即可提供5'- O，8-环嘌呤核苷，产率高达90％。该方法使用了廉价的CuCl催化剂和二叔丁基过氧化物（DTBP）氧化剂，适用于广泛的底物范围，即使以克为单位，也能很好地进行。
• Inhibition of Siderophore Biosynthesis in <i>Mycobacterium tuberculosis</i> with Nucleoside Bisubstrate Analogues: Structure−Activity Relationships of the Nucleobase Domain of 5′-<i>O</i>-[<i>N</i>-(Salicyl)sulfamoyl]adenosine
  作者：João Neres、Nicholas P. Labello、Ravindranadh V. Somu、Helena I. Boshoff、Daniel J. Wilson、Jagadeshwar Vannada、Liqiang Chen、Clifton E. Barry、Eric M. Bennett、Courtney C. Aldrich

  DOI：10.1021/jm800567v

  日期：2008.9.11

  5'-O-[N-(salicyl)sulfamoyl]adenosine (Sal-AMS) is a prototype for a new class of antitubercular agents that inhibit the aryl acid adenylating enzyme (AAAE) known as MbtA involved in biosynthesis of the mycobactins. Herein, we report the structure-based design, synthesis, biochemical, and biological evaluation of a comprehensive and systematic series of analogues, exploring the structure-activity relationship

  5'-O-[N-(水杨基)氨磺酰基]腺苷 (Sal-AMS) 是一类新型抗结核药物的原型，可抑制参与分枝杆菌素生物合成的称为 MbtA 的芳酸腺苷酸化酶 (AAAE)。在此，我们报告了一系列全面系统的类似物的基于结构的设计、合成、生化和生物学评估，探索了 Sal-AMS 嘌呤核碱基结构域的构效关系。值得注意的是，2-苯基-Sal-AMS 衍生物 26 表现出异常有效的抗结核活性，在 0.049 microM 的缺铁条件下具有 MIC99，而 N-6-环丙基-Sal-AMS 16 导致提高的效力和 64-增强铁缺乏条件下相对于铁充足条件下的活性，与设计的作用机制一致的表型。
• α,β-Methylene-ADP (AOPCP) Derivatives and Analogues: Development of Potent and Selective <i>ecto</i>-5′-Nucleotidase (CD73) Inhibitors
  作者：Sanjay Bhattarai、Marianne Freundlieb、Jan Pippel、Anne Meyer、Aliaa Abdelrahman、Amelie Fiene、Sang-Yong Lee、Herbert Zimmermann、Gennady G. Yegutkin、Norbert Sträter、Ali El-Tayeb、Christa E. Müller

  DOI：10.1021/acs.jmedchem.5b00802

  日期：2015.8.13

  ecto-5'-Nucleotidase (eN, CD73) catalyzes the hydrolysis of extracellular AMP to adenosine. eN inhibitors have potential for use as cancer therapeutics. The eN inhibitor alpha,beta-methylene-ADP (AOPCP, adenosine-5'-O-[(phosphonomethyl)phosphonic acid]) was used as a lead structure, and derivatives modified in various positions were prepared. Products were tested at rat recombinant eN. 6-(Ar)alkylamino substitution led to the largest improvement in potency. N-6-Monosubstitution was superior to symmetrical N-6,N-6-disubstitution. The most potent inhibitors were N-6-(4chlorobenzyl)-(10l, PSB-12441, K-i 7.23 n.M), N-6-phenylethyl(10h, PSB-12425, K-i 8.04 nM), and N-6-benzyl-adenosine-5'-O[(phosphonomethyl)phosphonic acid] (10g, PSB-12379, K-i 9.03 nM). Replacement of the 6-NH group in 10g by 0 (10q, PSB-12431) or S (10r, PSB-12553) yielded equally potent inhibitors (10q, 9.20 nM; 10r, 9.50 aM). Selected compounds investigated at the human enzyme did not show species differences; they displayed high selectivity versus other ecto-nudeotidases and ADP-activated P2Y receptors. Moreover, high metabolic stability was observed. These compounds represent the most potent eN inhibitors described to date.