4-amino-5-fluoro-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine | 750598-20-0

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 吡咯并嘧啶核苷和核苷酸
• 英文名称: 4-amino-5-fluoro-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine
• 英文别名: 7-fluoro-7-deaza-adenosine；7-fluoro-7-deazaadenosine；7-fluoro-D-tubercidin；5-fluorotubercidin；7-fluorotubercidin；4-amino-5-fluoro-7-(β-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine nucleoside；(2R,3R,4S,5R)-2-(4-Amino-5-fluoro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol；(2R,3R,4S,5R)-2-(4-amino-5-fluoropyrrolo[2,3-d]pyrimidin-7-yl)-5-(hydroxymethyl)oxolane-3,4-diol
• CAS: 750598-20-0
• 化学式: C₁₁H₁₃FN₄O₄
• 分子量: 284.247
• InChiKey: KRRZKBNCONNKPI-IOSLPCCCSA-N

物化性质

• 熔点：
  221-222 °C
• 沸点：
  650.2±55.0 °C(Predicted)
• 密度：
  1.99±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.2
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  127
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-amino-5-fluoro-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine 在 三氯硫磷 、 三辛胺 、 磷酸三乙酯 、 三丁基焦磷酸铵 作用下， 反应 2.0h， 生成
  参考文献：
  名称：

  Fluorine Substituted Adenosines As Probes of Nucleobase Protonation in Functional RNAs

  摘要：

  Ionized nucleobases are required for folding, conformational switching, or catalysis in a number of functional RNAs. A common strategy to study these sites employs nucleoside analogues with perturbed pK(a), but the interpretation of these studies is often complicated by the chemical modification introduced, in particular modifications that add, remove, or translocate hydrogen bonding groups in addition to perturbing pKa values. In the present study we present a series of fluorine substituted adenosine analogues that produce large changes in N1 pK(a) values with minimal structural perturbation. These analogues include fluorine for hydrogen substitutions in the adenine ring of adenosine and 7-deaza-adenosine with resulting N1 pK(a) values spanning more than 4 pKa units. To demonstrate the utility of these analogues we have conducted a nucleotide analogue interference mapping (NAIM) study on a self-ligating construct of the Varkud Satellite (VS) ribozyme. We find that each of the analogues is readily incorporated by T7 RNA polymerase and produces fully active transcripts when substituted at the majority of sites. Strong interferences are observed for three sites known to be critical for VS ribozyme function, most notably A756. Substitutions at A756 lead to slight enhancements in activity for elevated pK(a) analogues and dramatic interferences in activity for reduced pK(a) analogues, supporting the proposed catalytic role for this base. The structural similarity of these analogues, combined with their even incorporation and selective interference, provides an improved method for identifying sites of adenosine protonation in a variety of systems.

  DOI：

  10.1021/ja803336y
• 作为产物：
  描述：

  4-氯-5-氟-7H-吡咯并[2,3-D]-嘧啶 在 N,O-双三甲硅基乙酰胺 、 三氟甲磺酸三甲基硅酯 、 氨 作用下， 以 1,4-二氧六环 、 乙腈 为溶剂， 反应 15.0h， 生成 4-amino-5-fluoro-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine
  参考文献：
  名称：

  5-氟结核菌素的合成及生物活性

  摘要：

  研究了 4-氯吡咯并 [2,3-d] 嘧啶 (1) 的亲电氟化作用，最终使用 Selectfluor 将化合物 1 转化为 4-氯-5-氟吡咯并 [2,3-d] 嘧啶 (2) 的转化率为 59%。这种转化是通过 4-氯-5,6-二氢-5-氟-6-羟基吡咯并[2,3-d]嘧啶 (3) 以 9:1 的反式:顺式比例进行的。通过 1H NMR 和 19F NMR 研究了化合物 3 的反式异构体，并观察到 ​​5-H 互变异构体 (4) 作为另一个中间体。化合物2和四-O-乙酰核糖的改良Vorbruggen程序得到4-氯-5-氟-7-(2,3,5,-tri-O-苯甲酰基-β-d-呋喃核糖基)吡咯并[2,3- d]嘧啶 (6)，产率为 65%。在二恶烷中用氨 (l) 处理化合物 6 得到 5-氟结核菌素 (7)。未观察到抗菌活性。针对 Huh-7 肝细胞的 MTT 测定（Promega），用 Con

  DOI：

  10.1081/ncn-120027825

文献信息

• New small molecule inhibitors of histone methyl transferase DOT1L with a nitrile as a non-traditional replacement for heavy halogen atoms
  作者：Sophie S. Spurr、Elliott D. Bayle、Wenyu Yu、Fengling Li、Wolfram Tempel、Masoud Vedadi、Matthieu Schapira、Paul V. Fish

  DOI：10.1016/j.bmcl.2016.07.041

  日期：2016.9

  where the polar 5-nitrile group was shown by crystallography to bind in the hydrophobic pocket of DOT1L. In addition, we show that a polar nitrile group can be used as a non-traditional replacement for heavy halogen atoms.

  公开了许多新的核苷衍生物作为DOT1L活性的抑制剂。SARs证实，可以通过在5位（5、6、12）掺入极性基团和小的杂环或通过使用其他含氮碱基（18）来实现DOT1L抑制。根据这些结果，CN-SAH（19）被确定为DOT1L活性的有效和选择性抑制剂，其中结晶晶体显示极性5腈基结合在DOT1L的疏水口袋中。此外，我们表明极性腈基可以用作重卤素原子的非传统替代物。
• Cyclic di-nucleotide compounds as sting agonists
  申请人：Merck Sharp & Dohme Corp.

  公开号：US10106574B2

  公开（公告）日：2018-10-23

  A class of polycyclic compounds of general formula (I), of general formula (I′), or of general formula (I″), wherein Base1, Base2, Y, Ya, Xa, Xa1, Xb, Xb1, Xc, Xc1, Xd, Xd1, R1, R1a, R2, R2a, R3, R4, R4a, R5, R6, R6a, R7, R7a, R8, and R8a are defined herein, that may be useful as inductors of type I interferon production, specifically as STING active agents, are provided. Also provided are processes for the synthesis and use of compounds.

  一类通式(I)、通式(I′)或通式(I″)的多环化合物，其中Base1、Base2、Y、Ya、Xa、Xa1、Xb、Xb1、Xc、Xc1、Xd、Xd1、R1、R1a、R2、本文定义的 R2a、R3、R4、R4a、R5、R6、R6a、R7、R7a、R8 和 R8a 可用作 I 型干扰素产生的诱导剂，特别是 STING 活性剂。还提供了合成和使用这些化合物的工艺。
• Cyclic di-nucleotide compounds as STING agonists
  申请人：Merck Sharp & Dohme Corp.

  公开号：US10759825B2

  公开（公告）日：2020-09-01

  A class of polycyclic compounds of general formula (I), of general formula (I′), or of general formula (I″), wherein Base1, Base2, Y, Ya, Xa, Xa1, Xb, Xb1, Xc, Xc1, Xd, Xd1, R1, R1a, R2, R2a, R3, R4, R4a, R5, R6, R6a, R7, R7a, R8, and R8a are defined herein, that may be useful as inductors of type I interferon production, specifically as STING active agents, are provided. Also provided are processes for the synthesis and use of compounds.

  一类通式(I)、通式(I′)或通式(I″)的多环化合物，其中Base1、Base2、Y、Ya、Xa、Xa1、Xb、Xb1、Xc、Xc1、Xd、Xd1、R1、R1a、R2、本文定义的 R2a、R3、R4、R4a、R5、R6、R6a、R7、R7a、R8 和 R8a 可用作 I 型干扰素产生的诱导剂，特别是 STING 活性剂。还提供了合成和使用这些化合物的工艺。
• [EN] METHODS FOR THE PREPARATION OF 5-FLUORO-PYRROLO[2,3-d]PYRIMIDINE COMPOUNDS<br/>[FR] PROCEDES DE PREPARATION DE COMPOSES 5-FLUORO-PYRROLO[2,3-D]PYRIMIDINE
  申请人：ISIS PHARMACEUTICALS INC

  公开号：WO2005016878A3

  公开（公告）日：2005-06-02
• CYCLIC DI-NUCLEOTIDE COMPOUNDS AS STING AGONISTS
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP3334745A1

  公开（公告）日：2018-06-20