5-O-benzoyl-2,3-dideoxy-2-fluoro-α-D-arabinofuranosyl bromide | 136228-19-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-O-benzoyl-2,3-dideoxy-2-fluoro-α-D-arabinofuranosyl bromide
• 英文别名: [(2S,4S,5R)-5-bromo-4-fluorooxolan-2-yl]methyl benzoate
• CAS: 136228-19-8
• 化学式: C₁₂H₁₂BrFO₃
• 分子量: 303.128
• InChiKey: ZBESIJKGLHBFCJ-DCAQKATOSA-N

物化性质

• 沸点：
  350.5±42.0 °C(Predicted)
• 密度：
  1.51±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-O-benzoyl-2,3-dideoxy-2-fluoro-α-D-arabinofuranosyl bromide 在 甲醇 、 氨 作用下， 以 甲醇 为溶剂， 反应 4.0h， 生成 1-(2,3-二脱氧-2-氟呋喃戊糖基)胞嘧啶
  参考文献：
  名称：

  2'-氟-2'，3'-双脱氧阿拉伯呋喃糖基嘧啶的化学性质和抗HIV特性。

  摘要：

  为了寻找有用的抗爱滋病药物，已经研究了一系列1-（2,3-二脱氧-2-氟-β-D-thopenopentofuranosyl）pyrimidines的合成，化学，生物化学和抗HIV活性。通过2，3-二脱氧核糖中间体进行合成，该中间体通过在与尿嘧啶或胞嘧啶糖苷配子缩合之前而不是之后除去糖的3'-羟基来促进类似物的制备。2'-F-dd-尿苷类似物7a-d（在5位上具有H，F，Cl和CH3取代）以及4-脱氧化合物（12b）对感染了ATH8或CEM的细胞无保护作用HIV-1。在相应的胞苷系列中，5-氯类似物（11）没有活性。然而，2′-氟-2′，3′-二脱氧阿拉伯糖基胞嘧啶10a和其5-氟类似物10b都具有活性。虽然这两种化合物都不具有像ddC或5-F-ddC那样的强效作用（2b），但10b可以完全抵抗两种宿主细胞系中HIV的细胞病变作用。2'-氟取代赋予双脱氧核苷化学和酶稳定性。尽管双脱氧嘧啶核

  DOI：

  10.1021/jm00090a008
• 作为产物：
  描述：

  [(3aR,5S,6aR)-2,2-dimethyltetrhydrofuro[2,3-d][1,3]dioxol-5-yl]methyl benzoate 在 二乙胺基三氟化硫 、 硫酸 、 氢溴酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 6.0h， 生成 5-O-benzoyl-2,3-dideoxy-2-fluoro-α-D-arabinofuranosyl bromide
  参考文献：
  名称：

  Enhanced Brain Delivery of an Anti-HIV Nucleoside 2'-F-ara-ddI by Xanthine Oxidase Mediated Biotransformation

  摘要：

  In order to enhance the brain delivery of 2'-F-ara-ddI, 2'-F-ara-ddP 6 was synthesized and its in vitro and in vivo bioconversion reaction studied. For the study, a new efficient synthetic method for 2'-F-ara-ddP 6 was developed from 5-benzoyl-1,2-0-isopropylidene-3-deoxyribose 1. For in vitro study 2'-F-ara-ddP was incubated in pH 2, mouse liver homogenate, and mouse serum at 37-degrees-C. No degradation was observed in pH 2 and serum, while in liver homogenate 2'-F-ara-ddP was almost completely converted to 2'-F-ara-ddI within 20 min (t1/2 = 3.54 min). In order to determine the role of xanthine oxidase in the conversion of 2'-F-ara-ddP to 2'-F-ara-ddI, in vitro studies were conducted in phosphate buffer (pH 7.4) in the presence or absence of allopurinol, in which the half-lives of 2'-F-ara-ddP were 7.4 and 3.4 h, respectively, indicating the conversions were catalyzed by the xanthine oxidase. A similar experiment with aldehyde oxidase isolated from the human liver did not affect the biotransformation. The biotransformation was also detected in the brain homogenate, although the rate of conversion was low and incomplete. In order to assess the bioconversion in vivo, pharmacokinetic studies of 2'-F-ara-ddP and 2'-F-ara-ddI were conducted in mice. The maximum serum concentrations of 2'-F-ara-ddI administered itself and as 2'-F-ara-ddP reached 48.1 +/- 10.00 and 89.3 +/- 26.0 muM and were observed in 1 and 0.25 h, respectively. The data indicate that 2'-F-ara-ddI is absorbed at a slower rate than that of 2'-F-ara-ddP. The bioavailability of the prodrug after oral administration was 60.7 %. The concentration of 2'-F-ara-ddI following oral administration of 2'-ara-ddI was close to the detection limits while 2'-F-ara-ddI was detected at significantly higher concentrations in the brain after oral administration of 2'-F-ara-ddP. From this study, we have administered the enhanced brain delivery of anti-HIV nucleoside utilizing an in vivo biotransformation system.

  DOI：

  10.1021/jm00032a017

文献信息

• [EN] INHIBITORS OF CD73-MEDIATED IMMUNOSUPPRESSION<br/>[FR] INHIBITEURS DE L'IMMUNOSUPPRESSION MÉDIÉE PAR CD73
  申请人：ARCUS BIOSCIENCES INC

  公开号：WO2018094148A1

  公开（公告）日：2018-05-24

  Compounds that modulate the conversion of AMP to adenosine by 5'- nucleotidase, ecto, and compositions containing the compounds and methods for synthesizing the compounds, are described herein. The use of such compounds and compositions for the treatment and/or prevention of a diverse array of diseases, disorders and conditions, including cancer- and immune-related disorders, that are mediated by 5'- nucleotidase, ecto is also provided.

  本文描述了调节AMP转化为腺苷的5'-核苷酸酶外切的化合物，以及含有这些化合物的组合物和合成这些化合物的方法。还提供了这些化合物和组合物用于治疗和/或预防多种疾病、紊乱和病况，包括由5'-核苷酸酶外切介导的癌症和免疫相关紊乱的用途。
• 4-Azido-2-pyrimidinone Nucleosides and Related Chemistry
  作者：Lakshmi P. Kotra、PingPing Wang、Michael G. Bartlett、Kirupa Shanmuganathan、Zusheng Xu、Sócrates Cavalcanti、M. Gary Newton、Chung K. Chu

  DOI：10.1021/jo970761t

  日期：1997.10.1

  The X-ray analysis indicated that compound 4 exists as 1-(beta-D-arabinofuranosyl)tetrazolo[4,5-c]pyrimidin-2-one, with the azide moiety cyclized. To understand if the chemical instability of the nucleoside 4 was due to the arabino configuration of 2'-OH or due to the azido moiety, we also studied 1-(2,3-dideoxy-2-fluoro-beta-D-arabinofuranosyl)tetrazolo[4,5-c]pyrimidin-2-one (11) and 4-azido-1-methyl-2-pyrimidinone

  作为叠氮化物前药方法的一部分，我们合成了ara-C的4-叠氮基类似物（4）作为ara-C的前药。从1-（β-D-阿拉伯呋喃糖基）尿嘧啶（1）中分三步得到化合物4。在pH值为7.0和11.0时，观察到化合物4的UV吸收损失，该转化通过一维，二维NMR和串联质谱研究鉴定转化产物5证明。在NMR研究中，在化合物4和5之间的5、6、1'和2'位置观察到了化学位移的变化。在质谱图中观察到m / z 270.1（MH（+））的分子峰鉴定化合物4和转化产物5。在180.2的片段被鉴定为化合物6，其包含化合物5的6,2'-脱水键。X射线分析表明，化合物4以1-（β-D-阿拉伯呋喃糖基）四唑并[4，5-c]嘧啶-2-一存在，叠氮化物部分被环化。为了了解核苷4的化学不稳定性是由于2'-OH的阿拉伯糖构型还是由于叠氮基部分，我们还研究了1-（2,3-dideoxy-2-fluoro-beta-D-arabinofuranosyl）四唑并[4
• Wysocki Jr.; Siddiqui; Barchi Jr., Synthesis, 1991, # 11, p. 1005 - 1008
  作者：Wysocki Jr.、Siddiqui、Barchi Jr.、Driscoll、Marquez

  DOI：——

  日期：——
• Chemistry and Anti-HIV Activity of 2′-β-Fluoro-2′,3′-dideoxyguanosine
  作者：Harry Ford、John S. Driscoll、Maqbool Siddiqui、James A. Kelley、Hioraki Mitsuya、Takuma Shirasaka、David G. Johns、Victor E. Marquez

  DOI：10.1080/15257779408013236

  日期：1994.3

  The 2'-beta-fluoro analogue of 2',3'-dideoxyguanosine has been prepared by two synthetic routes. This compound and two analogues have anti-HIV activity in at least two of three host cell systems used (ATH8, CEM, PEL). These compounds, as well as their ddGuo parents, have been characterized with regard to their acid-stabilities, octanol-water partition coefficients, and enzyme substrate properties for adenosine deaminase and purine nucleoside phosphorylase. F-ddGuo analogues are less potent but more stable than their non-fluorinated parent compounds.
• CYCLIC DINUCLEOTIDES AS ANTICANCER AGENTS
  申请人：Bristol-Myers Squibb Company

  公开号：EP3658565B1

  公开（公告）日：2022-11-09