4-chloro-5-iodo-7-(5'-O-tert-butyldimethylsilyl-2',3'-O-isopropylidene-β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine | 291535-38-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 英文名称: 4-chloro-5-iodo-7-(5'-O-tert-butyldimethylsilyl-2',3'-O-isopropylidene-β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine
• 英文别名: 4-chloro-5-iodo-7-(5-tert-butyldimethylsilyl-2,3-O-isopropylidene-β-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine；4-chloro-5-iodo-7-(5'-O-tert-butyldimethylsilyl-2',3'-O-iso-β-D-propylidene-β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine；4-chloro-5-iodo-7-[5-O-[(1,1-dimethylethyl)dimethysilyl]-2,3-O-(1-methylethylidene)-β-D-ribofuranosyl]-7H-pyrrolo[2,3-d]pyrimidine；7-(5-O-tert-butyldimethylsilyl-2,3-O-isopropylidene-β-D-ribofuranosyl)-4-chloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidine；[(3aR,4R,6R,6aR)-4-(4-chloro-5-iodopyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methoxy-tert-butyl-dimethylsilane
• CAS: 291535-38-1
• 化学式: C₂₀H₂₉ClIN₃O₄Si
• 分子量: 565.911
• InChiKey: BLWPIACCJPPZNL-SCFUHWHPSA-N

物化性质

• 沸点：
  575.2±50.0 °C(Predicted)
• 密度：
  1.58±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.13
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  67.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-chloro-5-iodo-7-(5'-O-tert-butyldimethylsilyl-2',3'-O-isopropylidene-β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine 在 potassium carbonate 、 三氟乙酸 作用下， 以 甲醇 为溶剂， 反应 12.0h， 生成 4-methoxy-5-iodo-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine
  参考文献：
  名称：

  Study on the Synthesis and PKA-I Binding Activities of 5-Alkynyl Tubercidin Analogues

  摘要：

  5-Alkynyl tubercidin analogues were synthesized and their biological activities were evaluated. It was found that protein kinase A could be activated by 5-alkynyl tubercidin (9a) and cAMP-binding ability to PKA-I was selectively inhibited by it. Molecular modeling showed that the interaction of 9a and PKA-I was associated with the existence of hydrophobic alkynyl group, During (he synthesis of tubercidin analogues, a pair of 2'-carbonyl participating abnormal coupling products (11a, 11b) was obtained, the structure was identified by X-ray crystalline diffraction. (C). 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00341-8
• 作为产物：
  描述：

  4-氯吡咯并嘧啶 在 N-碘代丁二酰亚胺 、 sodium hydride 作用下， 反应 44.0h， 生成 4-chloro-5-iodo-7-(5'-O-tert-butyldimethylsilyl-2',3'-O-isopropylidene-β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine
  参考文献：
  名称：

  Study on the Synthesis and PKA-I Binding Activities of 5-Alkynyl Tubercidin Analogues

  摘要：

  5-Alkynyl tubercidin analogues were synthesized and their biological activities were evaluated. It was found that protein kinase A could be activated by 5-alkynyl tubercidin (9a) and cAMP-binding ability to PKA-I was selectively inhibited by it. Molecular modeling showed that the interaction of 9a and PKA-I was associated with the existence of hydrophobic alkynyl group, During (he synthesis of tubercidin analogues, a pair of 2'-carbonyl participating abnormal coupling products (11a, 11b) was obtained, the structure was identified by X-ray crystalline diffraction. (C). 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00341-8

文献信息

• A 7-Deazaadenosylaziridine Cofactor for Sequence-Specific Labeling of DNA by the DNA Cytosine-C5 Methyltransferase M.HhaI
  作者：Falk Kunkel、Rudi Lurz、Elmar Weinhold

  DOI：10.3390/molecules201119723

  日期：——

  transfer of the activated methyl group of the cofactor S-adenosyl-l-methionine (AdoMet or SAM) to the exocyclic amino groups of adenine or cytosine or the C5 ring atom of cytosine within specific DNA sequences. The DNA adenine-N6 MTase from Thermus aquaticus (M.TaqI) is also capable of coupling synthetic N-adenosylaziridine cofactor analogues to its target adenine within the double-stranded 5′-TCGA-3′

  DNA 甲基转移酶 (MTases) 催化辅助因子 S-腺苷-1-甲硫氨酸（AdoMet 或 SAM）的活化甲基转移到特定 DNA 序列中腺嘌呤或胞嘧啶的环外氨基或胞嘧啶的 C5 环原子。来自水生栖热菌 (M.TaqI) 的 DNA 腺嘌呤-N6 MTase 还能够将合成的 N-腺苷氮丙啶辅因子类似物与其双链 5'-TCGA-3' 序列内的靶腺嘌呤偶联。利用这种 M.TaqI 介导的偶联反应，使用在腺嘌呤环的 8 位带有报告基团的 N-腺苷氮丙啶衍生物，将荧光团和生物素序列特异性地传递到 DNA 中。然而，这些 8 修饰的氮丙啶辅因子是来自溶血性嗜血杆菌 (M.HhaI) 的 DNA 胞嘧啶-C5 MTase 的不良底物。基于 M 的晶体结构。HhaI 与双链寡脱氧核苷酸和辅因子产物复合，我们合成了稳定的 7-脱氮腺苷氮丙啶衍生物，生物素基团通过灵活的接头连接到 7 位。这种 7 修饰的氮丙啶辅因子可以被
• Adenosine Kinase Inhibitors. 1. Synthesis, Enzyme Inhibition, and Antiseizure Activity of 5-Iodotubercidin Analogues
  作者：Bheemarao G. Ugarkar、Jay M. DaRe、Joseph J. Kopcho、Clinton E. Browne、Juergen M. Schanzer、James B. Wiesner、Mark D. Erion

  DOI：10.1021/jm000024g

  日期：2000.7.1

  side effects. Adenosine kinase inhibitors (AKIs) represent an alternative strategy, since AKIs may raise local adenosine levels in a more site- and event-specific manner and thereby elicit the desired pharmacology with a greater therapeutic window. Starting with 5-iodotubercidin (IC50 = 0.026 microM) and 5'-amino-5'-deoxyadenosine (IC50 = 0.17 microM) as lead inhibitors of the isolated human AK, a variety

  腺苷受体激动剂产生多种治疗上有用的药理学。然而，迄今为止，由于剂量限制的副作用，它们未能成功进行临床开发。腺苷激酶抑制剂（AKIs）代表了另一种策略，因为AKIs可以以更多位点和事件特异性的方式提高局部腺苷水平，从而以更大的治疗窗口引发所需的药理作用。从5-碘代小球蛋白（IC50 = 0.026 microM）和5'-氨基-5'-脱氧腺苷（IC50 = 0.17 microM）作为分离的人AK的主要抑制剂开始，各种吡咯并[2,3-d]嘧啶核苷类似物通过使用钠盐介导的糖基化方法将5-取代的4-取代的4-氯吡咯并[2,3-d]嘧啶碱基与核糖类似物偶联来设计和制备。5'-氨基-5' 发现5-溴和5-碘结核菌素的β-脱氧类似物是迄今为止报道的最有效的AKI（IC50S <0.001 microM）。在大鼠最大电击（MES）诱发的癫痫发作试验中，几种有效的AKIs表现出抗惊厥活性。
• Nucleoside compounds for treating viral infections
  申请人：Roberts D. Christopher

  公开号：US20060241064A1

  公开（公告）日：2006-10-26

  Disclosed are compounds, compositions and methods for treating viral infections caused by a Flaviviridae family virus, such as hepatitis C virus.

  揭示了用于治疗由黄病毒科病毒引起的病毒感染的化合物、组合物和方法，例如丙型肝炎病毒。
• Structure−Activity Relationships of 7-Deaza-6-benzylthioinosine Analogues as Ligands of<i>Toxoplasma gondii</i>Adenosine Kinase
  作者：Young Ah Kim、Ashoke Sharon、Chung K. Chu、Reem H. Rais、Omar N. Al Safarjalani、Fardos N. M. Naguib、Mahmoud H. el Kouni

  DOI：10.1021/jm800201s

  日期：2008.7

  Several 7-deaza-6-benzylthioinosine analogues with varied substituents on aromatic ring were synthesized and evaluated against Toxoplasma gondii adenosine kinase (EC.2.7.1.20). Structure-activity relationships indicated that the nitrogen atom at the 7-position does not appear to be a critical structural requirement. Molecular modeling reveals that the 7-deazapurine motif provided flexibility to the 6-benzylthio group as a result of the absence of H-bonding between N7 and Thr140. This flexibility allowed better fitting of the 6-benzylthio group into the hydrophobic pocket of the enzyme at the 6-position. In general, single substitutions at the para or meta position enhanced binding. On the other hand., single substitutions at the ortho position led to the loss of binding affinity. The most potent compounds, 7-deaza-p-cyano-6-benzylthioinosine (IC(50) = 5.3 mu M) and 7-deaza-p-methoxy-6-benzylthioinosine (IC(50) = 4.6 mu M), were evaluated in cell culture to delineate their selective toxicity.
• Adenosine Kinase Inhibitors. 2. Synthesis, Enzyme Inhibition, and Antiseizure Activity of Diaryltubercidin Analogues
  作者：Bheemarao G. Ugarkar、Angelo J. Castellino、Jay M. DaRe、Joseph J. Kopcho、James B. Wiesner、Juergen M. Schanzer、Mark D. Erion

  DOI：10.1021/jm0000259

  日期：2000.7.1

  In the preceding article (Ugarkar et al. J. Med. Chem. 2000, 43) we reported that analogues of tubercidin are potent adenosine kinase (AK) inhibitors with antiseizure activity in the rat maximum electroshock (MES) model. Despite the discovery of several highly potent AK inhibitors (AKIs), e.g., 5'-amino-5'-deoxy-5-iodotubercidin (1c) (IC50 = 0.0006 mu M), no compounds were identified that exhibited a safety, efficacy, and side effect profile suitable for further development. In this article, we demonstrate that substitution of the tubercidin molecule with aromatic rings at the N4- and the C5-positions not only retains AKI potency but also improves in vivo activity. Synthesis of such compounds entailed transformation of 4-arylanlino-5-iodotubercidin analogues to their corresponding 5-aryl derivatives via the Suzuki reaction. Alternatively, 4-N-suylamino-5-arylpyrrolo[2,3-d]pyrimdine bases were constructed and then glycosylated with appropriately protected alpha-ribofuranosyl chlorides using a phase-transfer catalyst. Several compounds exhibited potent activity in the rat MES seizure assay with ED(50)s less than or equal to 2.0 mg/kg, ip, and showed relatively mild side effects.