9-(2-deoxy-2-fluoro-4-thio-α,β-D-arabino-pentofuranosyl)-2,6-diaminopurine | 248601-56-1

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: 9-(2-deoxy-2-fluoro-4-thio-α,β-D-arabino-pentofuranosyl)-2,6-diaminopurine
• 英文别名: 9-(2-deoxy-2-fluoro-4-thio-D-arabinofuranosyl)-2,6-diaminopurine；(2R,3S,4S)-5-(2,6-diaminopurin-9-yl)-4-fluoro-2-(hydroxymethyl)thiolan-3-ol
• CAS: 248601-56-1
• 化学式: C₁₀H₁₃FN₆O₂S
• 分子量: 300.317
• InChiKey: CHJNRPSUWOMJIA-VPRFCXCPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  161
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  9-(2-deoxy-2-fluoro-4-thio-α,β-D-arabino-pentofuranosyl)-2,6-diaminopurine 在 adenosine deaminase 作用下， 以 various solvent(s) 为溶剂， 反应 6.0h， 以42%的产率得到9-(2-deoxy-2-fluoro-4-thio-β-D-arabino-pentofuranosyl)guanine
  参考文献：
  名称：

  2'-脱氧-2'-氟-4'-硫代阿拉伯呋喃糖基嘧啶和-嘌呤核苷的合成及生物活性。

  摘要：

  作为我们正在进行的生物学上有趣的2'-修饰的4'-硫代核苷合成研究的一部分，我们合成了2'-脱氧-2'-氟-4'-硫代阿拉伯呋喃糖基嘧啶和-嘌呤核苷，并评估了它们的抗病毒和抗肿瘤活性。在嘧啶系列中，5-乙基尿嘧啶，5-碘尿嘧啶，5-氯乙基尿嘧啶和5-碘胞嘧啶衍生物的β-端基异构体在体外显示有效和选择性的抗HSV-1和HSV-2活性。在嘌呤系列中，鸟嘌呤和2,6-二氨基嘌呤衍生物显示出显着的抗病毒活性，并具有轻微的细胞毒性。另一方面，5-氟胞嘧啶衍生物（5F-4'-thioFAC）对白血病和实体瘤均显示出有效的抗肿瘤活性。将其针对14种人实体瘤和一种白血病细胞系的抗肿瘤谱与4' -thioFAC。结果显示5F-4'-thioFAC具有与4'-thioFAC相似的抗肿瘤光谱。但是，5F-4'-thioFAC的活性比4'-thioFAC低约10倍。

  DOI：

  10.1016/s0968-0896(00)00065-1
• 作为产物：
  描述：

  2,6-二氨基嘌呤 在 氨 作用下， 以 甲醇 、 水 为溶剂， 生成 9-(2-deoxy-2-fluoro-4-thio-α,β-D-arabino-pentofuranosyl)-2,6-diaminopurine
  参考文献：
  名称：

  An Alternative Synthesis of the Antineoplastic Nucleoside 4‘-ThioFAC and Its Application to the Synthesis of 4‘-ThioFAG and 4‘-Thiocytarazid

  摘要：

  Previously, we synthesized 4'-thioFAC, a novel antineoplastic cytosine nucleoside, by developing an original method. However, several problems remained. To overcome these problems, we have developed an alternative method far the synthesis of 4'-thionucleosides. In the original synthesis, carbons from C1 to C5 of D-glucose were used. The new method also starts from D-glucose but uses carbons closer to the tail (C2-C6). A dibenzoyl derivative obtained by this approach was brominated at the anomeric position to give a 1-bromide derivative. Fusion of the I-bromide and persilylated acetylcytosine, followed by deprotection, predominantly gave a beta-anomer of 4'-thioFAC. The reaction of 2,6-diaminopurine with the I-bromide in the presence of TMS triflate gave a glycosylated product in good yield. After deprotection, the resulting 1:1 anomeric mixture of free nucleosides was treated with adenosine deaminase to give a beta-anomer of 4'-thioFAG, a guanine congener of 4'-thioFAC, selectively. Using a similar approach, we synthesized 4'-thiocytarazid, which was not possible using the original method.

  DOI：

  10.1021/jo990958g

文献信息

• 9-(2-deoxy-2-fluoro-4-thio-beta-D-arabinofuranosyl)purine derivatives
  申请人：Yamasa Corporation

  公开号：US06103707A1

  公开（公告）日：2000-08-15

  The present invention relates to 9-(2-deoxy-2-fluoro-4-thio-beta-D-arabinofuranosyl)purine derivatives having antiviral activity, represented by formula [I]: ##STR1## wherein B represents a base selected from the group consisting of purine, azapurine and deazapurine, which may be substituted with halogen, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, amino, alkylamino, hydroxyl, hydroxyamino, aminoxy, alkoxy, mercapto, alkylmercapto, aryl, aryloxy or cyano; and R represents a hydrogen atom or a phosphoric acid residue, and to a process for the production and use thereof.

  本发明涉及具有抗病毒活性的9-(2-去氧-2-氟-4-硫-β-D-阿拉伯呋喃糖基)嘌呤衍生物，其表示为公式[I]：##STR1## 其中B代表从嘌呤、氮杂嘌呤和去氮杂嘌呤中选择的碱基，可以用卤素、烷基、卤代烷基、烯基、卤代烯基、炔基、氨基、烷基氨基、羟基、羟基氨基、氨氧基、烷氧基、巯基、烷基巯基、芳基、芳基氧基或氰基进行取代；R代表氢原子或磷酸残基，并提供一种制备和使用它们的方法。
• 9-(2-DEOXY-2-FLUORO-4-THIO-BETA-D-ARABINOFURANOSYL)PURINE DERIVATIVES
  申请人：YAMASA CORPORATION

  公开号：EP0839813A1

  公开（公告）日：1998-05-06

  The present invention relates to 9-(2-deoxy-2-fluoro-4-thio-beta-D-arabinofuranosyl)purine derivatives having antiviral activity, represented by formula [I]: wherein B represents a base selected from the group consisting of purine, azapurine and deazapurine, which may be substituted with halogen, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, amino, alkylamino, hydroxyl, hydroxyamino, aminoxy, alkoxy, mercapto, alkylmercapto, aryl, aryloxy or cyano; and R represents a hydrogen atom or a phosphoric acid residue, and to a process for the production and use thereof.

  本发明涉及具有抗病毒活性的 9-(2-脱氧-2-氟-4-硫代-beta-D-阿拉伯呋喃糖基)嘌呤衍生物，由式[I]表示： 其中 B 代表选自嘌呤、氮杂嘌呤和去氮杂嘌呤的碱基，可被卤素、烷基、卤代烷基、烯基、卤代烯基、炔基、氨基、烷基氨基、羟基、羟基氨基、氨基氧基、烷氧基、巯基、烷基巯基、芳基、芳氧基或氰基取代；R 代表氢原子或磷酸残基，并涉及其生产和使用过程。
• US6103707A
  申请人：——

  公开号：US6103707A

  公开（公告）日：2000-08-15
• An Alternative Synthesis of the Antineoplastic Nucleoside 4‘-ThioFAC and Its Application to the Synthesis of 4‘-ThioFAG and 4‘-Thiocytarazid
  作者：Yuichi Yoshimura、Mikari Endo、Shinji Miura、Shinji Sakata

  DOI：10.1021/jo990958g

  日期：1999.10.1

  Previously, we synthesized 4'-thioFAC, a novel antineoplastic cytosine nucleoside, by developing an original method. However, several problems remained. To overcome these problems, we have developed an alternative method far the synthesis of 4'-thionucleosides. In the original synthesis, carbons from C1 to C5 of D-glucose were used. The new method also starts from D-glucose but uses carbons closer to the tail (C2-C6). A dibenzoyl derivative obtained by this approach was brominated at the anomeric position to give a 1-bromide derivative. Fusion of the I-bromide and persilylated acetylcytosine, followed by deprotection, predominantly gave a beta-anomer of 4'-thioFAC. The reaction of 2,6-diaminopurine with the I-bromide in the presence of TMS triflate gave a glycosylated product in good yield. After deprotection, the resulting 1:1 anomeric mixture of free nucleosides was treated with adenosine deaminase to give a beta-anomer of 4'-thioFAG, a guanine congener of 4'-thioFAC, selectively. Using a similar approach, we synthesized 4'-thiocytarazid, which was not possible using the original method.
• Synthesis and biological activities of 2′-deoxy-2′-fluoro-4′-thioarabinofuranosylpyrimidine and -purine nucleosides
  作者：Yuichi Yoshimura、Kenji Kitano、Kohei Yamada、Shinji Sakata、Shinji Miura、Noriyuki Ashida、Haruhiko Machida

  DOI：10.1016/s0968-0896(00)00065-1

  日期：2000.7

  As part of our ongoing investigation of the synthesis of biologically interesting 2'-modified-4'-thionucleosides, we synthesized 2'-deoxy-2'-fluoro-4'-thioarabinofuranosylpyrimidine and -purine nucleosides, and evaluated their antiviral and antitumor activities. In the pyrimidine series, beta-anomers of 5-ethyluracil, 5-iodouracil, 5-chloroethyluracil, and 5-iodocytosine derivatives showed potent and

  作为我们正在进行的生物学上有趣的2'-修饰的4'-硫代核苷合成研究的一部分，我们合成了2'-脱氧-2'-氟-4'-硫代阿拉伯呋喃糖基嘧啶和-嘌呤核苷，并评估了它们的抗病毒和抗肿瘤活性。在嘧啶系列中，5-乙基尿嘧啶，5-碘尿嘧啶，5-氯乙基尿嘧啶和5-碘胞嘧啶衍生物的β-端基异构体在体外显示有效和选择性的抗HSV-1和HSV-2活性。在嘌呤系列中，鸟嘌呤和2,6-二氨基嘌呤衍生物显示出显着的抗病毒活性，并具有轻微的细胞毒性。另一方面，5-氟胞嘧啶衍生物（5F-4'-thioFAC）对白血病和实体瘤均显示出有效的抗肿瘤活性。将其针对14种人实体瘤和一种白血病细胞系的抗肿瘤谱与4' -thioFAC。结果显示5F-4'-thioFAC具有与4'-thioFAC相似的抗肿瘤光谱。但是，5F-4'-thioFAC的活性比4'-thioFAC低约10倍。