5'-deoxy-5-iodotubercidin | 85209-84-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5'-deoxy-5-iodotubercidin
• 英文别名: 4-amino-5-iodo-7-(5-deoxy-β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine；5-iodo-5'-deoxytubercidin；4-Amino-7-(5-deoxy-beta-D-ribofuranosyl)-5-iodo-7H-pyrrolo[2,3-d] pyrimidine；4-Amino-7-(5-deoxy-beta-D-ribofuranosyl)-5-iodo-7H-pyrrolo[2,3-d]pyrimidine；7-(5-Deoxy-Beta-D-Ribofuranosyl)-5-Iodo-7h-Pyrrolo[2,3-D]pyrimidin-4-Amine；(2R,3R,4S,5R)-2-(4-amino-5-iodopyrrolo[2,3-d]pyrimidin-7-yl)-5-methyloxolane-3,4-diol
• CAS: 85209-84-3
• 化学式: C₁₁H₁₃IN₄O₃
• 分子量: 376.154
• InChiKey: NTXUAWGNGBSCRS-TZQXKBMNSA-N

物化性质

• 熔点：
  242-243 °C
• 沸点：
  629.4±55.0 °C(Predicted)
• 密度：
  2.36±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  106
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5'-deoxy-5-iodotubercidin 、 苯硼酸 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 乙醇 、 二乙二醇二甲醚 为溶剂， 反应 4.0h， 以78%的产率得到(2R,3R,4S,5R)-2-(4-Amino-5-phenyl-pyrrolo[2,3-d]pyrimidin-7-yl)-5-methyl-tetrahydro-furan-3,4-diol
  参考文献：
  名称：

  Adenosine Kinase Inhibitors. 2. Synthesis, Enzyme Inhibition, and Antiseizure Activity of Diaryltubercidin Analogues

  摘要：

  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.

  DOI：

  10.1021/jm0000259
• 作为产物：
  描述：

  4-氯-5-碘-7H-吡咯并[2,3-d]嘧啶 在 甲醇 、 N,O-双三甲硅基乙酰胺 、 氨 作用下， 以 乙腈 为溶剂， 反应 13.42h， 生成 5'-deoxy-5-iodotubercidin
  参考文献：
  名称：

  通过Vorbrüggen糖基化高效合成5'-脱氧结核精及其类似物

  摘要：

  据报道以10克的规模有效有效地合成了天然存在的海洋核苷5'-脱氧结核菌素，其总收率良好。关键步骤是吡咯并[2,3- d ]嘧啶与5-脱氧-1,2,3-三-O-乙酰基-β - d-呋喃核糖的Vorbrüggen糖基化。 5'-脱氧tubercidin-Vorbrüggen糖基化-吡咯并[2,3- d ]嘧啶-海洋核苷-7-脱氮嘌呤

  DOI：

  10.1055/s-0030-1259975

文献信息

• 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。
• KAZLAUSKAS, R.
  作者：KAZLAUSKAS, R.

  DOI：——

  日期：——
• WATER-SOLUBLE ADENOSINE KINASE INHIBITORS
  申请人：Metabasis Therapeutics, Inc.

  公开号：EP0836613B1

  公开（公告）日：2005-05-25
• ORALLY ACTIVE ADENOSINE KINASE INHIBITORS
  申请人：Metabasis Therapeutics, Inc.

  公开号：EP0832092B1

  公开（公告）日：2004-11-17
• REGULATED BIOCIRCUIT SYSTEMS
  申请人：Obsidian Therapeutics, Inc.

  公开号：US20190192691A1

  公开（公告）日：2019-06-27

  The present invention provides regulatable biocircuit systems. Such systems provide modular and tunable protein expression systems in support of the discovery and development of therapeutic modalities.