9-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-N²-isobutyrylguanine | 308356-20-9

• 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: 9-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-N²-isobutyrylguanine
• 英文别名: N2-isobutyryl-9-(2'-deoxy-2'-fluoro-β-D-arabinofuranosyl)guanine；N-[9-[(2R,3S,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-oxo-1H-purin-2-yl]-2-methylpropanamide
• CAS: 308356-20-9
• 化学式: C₁₄H₁₈FN₅O₅
• 分子量: 355.326
• InChiKey: SLHADUUWJSVYGQ-NDORMNELSA-N

物化性质

• 密度：
  1.78±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  138
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  9-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-N²-isobutyrylguanine 在 咪唑 、 sodium azide 、 二苯基-2-吡啶膦 、 偶氮二甲酸二异丙酯 、 四丁基氟化铵 、 戴斯-马丁氧化剂 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 80.0h， 生成 9-(3'-azido-2'3'-dideoxy-2'-fluoro-β-D-arabinofuranosyl)guanine
  参考文献：
  名称：

  抗ウィルス薬

  摘要：

  This invention provides nucleoside analogs with excellent antiviral activity (especially anti-hepatitis B virus activity). The compound represented by the following formula (I): (wherein each symbol is as defined in the present specification) or its salt. No drawings are included.

  公开号：

  JP2020164521A
• 作为产物：
  描述：

  异丁酸酐 、 9-(2-脱氧-2-氟阿拉伯呋喃基)鸟嘌呤 在 吡啶 、 ammonium hydroxide 、 三甲基氯硅烷 作用下， 以70%的产率得到9-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-N²-isobutyrylguanine
  参考文献：
  名称：

  2'-氟修饰的核苷膦酸酯的合成及其抗HIV活性：GS-9148的类似物。

  摘要：

  合成了GS-9148 [5-（6-氨基-嘌呤-9-基）-4-氟-2,5-二氢呋喃-2-基氧基甲基]-膦酸（2'-Fd4AP）的修饰嘌呤类似物，他们的抗艾滋病毒效力进行了评估。鸟嘌呤类似物（2'-Fd4GP）的抗病毒活性与MT-2细胞中2'-Fd4AP的抗病毒活性相当，但选择性降低。

  DOI：

  10.1016/j.bmcl.2007.11.126

文献信息

• Nucleoside 5'-methylene phosphonates
  申请人：Gilead Sciences, Inc.

  公开号：US05672697A1

  公开（公告）日：1997-09-30

  Novel oligonucleotides analogs and nucleoside analogs as well as methods for their synthesis are described. The oligonucleotides are useful in diagnostic and therapeutic applications. The oligonucleotides are stable to nuclease degradation.

  描述了新型寡核苷酸类似物和核苷酸类似物以及它们的合成方法。这些寡核苷酸在诊断和治疗应用中非常有用。这些寡核苷酸对核酸酶降解具有稳定性。
• WO2020016782A5
  申请人：——

  公开号：WO2020016782A5

  公开（公告）日：2022-07-14
• The abundant DNA adduct N7-methyl deoxyguanosine contributes to miscoding during replication by human DNA polymerase η
  作者：Olive J. Njuma、Yan Su、F. Peter Guengerich

  DOI：10.1074/jbc.ra119.008986

  日期：2019.6

  Aside from abasic sites and ribonucleotides, the DNA adduct N-7-methyl deoxyguanosine (N-7-CH3 dG) is one of the most abundant lesions in mammalian DNA. Because N-7-CH3 dG is unstable, leading to deglycosylation and ring-opening, its miscoding potential is not well-understood. Here, we employed a 2 '-fluoro isostere approach to synthesize an oligonucleotide containing an analog of this lesion (N-7-CH3 2 '-F dG) and examined its miscoding potential with four Y-family translesion synthesis DNA polymerases (pols): human pol (hpol) eta, hpol kappa, and hpol iota and Dpo4 from the archaeal thermophile Sulfolobus solfataricus. We found that hpol eta and Dpo4 can bypass the N-7-CH3 2 '-F dG adduct, albeit with some stalling, but hpol kappa is strongly blocked at this lesion site, whereas hpol iota showed no distinction with the lesion and the control templates. hpol eta yielded the highest level of misincorporation opposite the adduct by inserting dATP or dTTP. Moreover, hpol eta did not extend well past an N-7-CH3 2 '-F dG:dT mispair. MS-based sequence analysis confirmed that hpol eta catalyzes mainly error-free incorporation of dC, with misincorporation of dA and dG in 5-10% of products. We conclude that N-7-CH3 2 '-F dG and, by inference, N-7-CH3 dG have miscoding and mutagenic potential. The level of misincorporation arising from this abundant adduct can be considered as potentially mutagenic as a highly miscoding but rare lesion.