2-氨基-6-氟嘌呤 | 34798-94-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 中文名称: 2-氨基-6-氟嘌呤
• 英文名称: 2-amino-6-fluoropurine
• 英文别名: 6-fluoro-7(9)H-purin-2-ylamine；2-Amino-6-fluorpurin；6-fluoro-7H-purin-2-amine
• CAS: 34798-94-2
• 化学式: C₅H₄FN₅
• 分子量: 153.119
• InChiKey: UEPHHWZTSMVBMM-UHFFFAOYSA-N

物化性质

• 熔点：
  206-208 °C
• 沸点：
  240.7±50.0 °C(Predicted)
• 密度：
  2.05

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  80.5
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  2-氨基-6-氟嘌呤 、 2',3'-二脱氧尿苷 反应 3.0h， 以21.7%的产率得到[(2S,5R)-5-(2-氨基-6-氟嘌呤-9-基)四氢呋喃-2-基]甲醇
  参考文献：
  名称：

  Escherichia coli mediated biosynthesis and in vitro anti-HIV activity of lipophilic 6-halo-2',3'-dideoxypurine nucleosides

  摘要：

  A series of 6-substituted 2',3'-dideoxypurine ribofuranosides (ddP) was enzymatically synthesized with live E. coli in an effort to enhance the lipophilicity of this class of anti-human immunodeficiency virus (HIV) compounds and thereby facilitate drug delivery into the central nervous system. All 6-halo-substituted ddPs were substantially more lipophilic, as defined by their octanol-water partition coefficient (P), than their nonhalogenated congeners 2',3'-dideoxyinosine (ddI) or 2',3'-dideoxyguanosine (ddG). For this class of compounds, log P's ranged from +0.5 to -1.2 in the following order: 6-iodo, 2-amino-6-iodo > 6-bromo, 2-amino-6-bromo > 6-chloro, 2-amino-6-chloro > 6-fluoro, 2-amino-6-fluoro >> ddG > ddI. These compounds were evaluated in vitro for ability to suppress the infectivity, replication, and cytopathic effect of HIV. 2-Amino-6-fluoro-, 2-amino-6-chloro-, and 6-fluoro-ddP exhibited a potent activity against HIV comparable to that of ddI or ddG and completely blocked the infectivity of HIV without affecting the growth of target cells. The comparative order of in vitro anti-HIV activity was 2-amino-6-fluoro, 2-amino-6-chloro, 6-fluoro > 2-amino-6-bromo > 2-amino-6-iodo, 6-chloro > 6-bromo > 6-iodo. These compounds also exhibited potent in vitro activity against HIV-2 and 3'-azido-3'-deoxythymidine-resistant HIV-1 variants. All 2-amino-6-halo-ddPs and 6-halo-ddPs were substrates for adenosine deaminase (ADA) and were converted to ddG or ddI, respectively. In the presence of the potent ADA inhibitor 2'-deoxycoformycin, 6-halo-substituted ddPs failed to exert an in vitro antiretroviral effect. These dideoxypurine nucleoside analogues represent a new class of lipophilic prodrugs of ddG and ddI that possess the potential for more effective therapy of HIV-induced neurologic disorders.

  DOI：

  10.1021/jm00109a012
• 作为产物：
  描述：

  (2-氨基嘌呤-6-基)三甲基氯化铵 在 potassium hydrogen difluoride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以0.12 g的产率得到2-氨基-6-氟嘌呤
  参考文献：
  名称：

  抗Ｂ型肝炎ウイルス剤

  摘要：

  提供含有核酸类似物作为有效成分的抗乙型肝炎病毒药物，以及用于预防或治疗乙型肝炎病毒相关疾病的药物。抗乙型肝炎病毒药物和乙型肝炎病毒相关疾病的预防或治疗药物包含以下式（1）所示的化合物或其前体（其中，R代表卤原子、氨基、甲氧基或氰基），或其药学上可接受的盐，或它们的溶剂物。【选择图】无

  公开号：

  JP2020147532A

文献信息

• Synthesis of Some Biologically Active Halogenopurines
  作者：Hu, Yu Lin、Liu, Xiang、Lu, Ming、Ge, Qiang、Liu, Xiao Bin

  DOI：10.5012/jkcs.2010.54.4.429

  日期：2010.8.20

  Guanine (1)으로부터 생물활성이 있는 halogenopurines계 화합물을 합성하였다. Guanine을 acetic anhydride와 반응시켜서 2,9-diacetylguanine (2-1)을 합성하여 얻어진 화합물을 $POCl_3$와 반응시켜서 화합물 3a를 합성하고, 다음 단계에서 2-amino-6-halogenopurines (3b-d)를 합성하였다. 2-Halogenopurines (2-2a-d, 4-2a-d, 5a-d)을 2-amino-6-substituted purines (1, 3a, 4-1)로부터 효율적으로 합성한 후에, 새로운 화합물인 2-2a, 2-2c, 2-2d, 4-2c, 4-2d, 5b, 5c 및 5d를 합성하였다. 합성한 화합물의 구조를 원소분석, $^1H$ NMR, mass spectral data로 확인하였으며, 합성한 화합물에 대한 항균 활성을 시험하였다. A series of some biologically active halogenopurines were synthesized from commercially available guanine (1). The reaction of guanine with acetic anhydride yielded 2,9-diacetylguanine (2-1) by acetylation reaction. Further treatment of 2-1 with $POCl_3$ by PEG-2000 phase transfer catalysis furnished the important compound 3a, then 2-amino-6-halogenopurines (3b-d) were obtained through chlorine-exchange halogenations between KX and 3a by TPPB phase transfer catalyst. Further, 2-halogenopurines (2-2a-d, 4-2a-d, 5a-d) were efficiently prepared from 2-amino-6-substituted purines (1, 3a, 4-1) via a diazotization catalyzed by their corresponding CuX, and some new compounds 2-2a, 2-2c, 2-2d, 4-2c, 4-2d, 5b, 5c and 5d have been discovered. The structures of synthesized compounds were mainly established on the basis of their elemental analysis, $^1H$ NMR, as well as their mass spectral data. All the title compounds were screened for their antifungal activities, and some of the compounds showed promising activity.

  鸟嘌呤 (1)으로부터 생물활성이 있는 卤嘌呤 계화합물을 합성하였다.Guanine을 acetic anhydride와 반응시켜서 2,9-diacetylguanine (2-1)을 합성하여 얻어진 화합물을 $POCl_3$와 반응시켜서 화합물 3a를 합성하고, 다음 단계에서 2-amino-6-halogenopurines (3b-d)를 합성하였다.2-amino-6-substituted purines (1, 3a, 4-1)로부터 효율적으로 합성한 후에, 새로운 화합물인 2-2a, 2-2c, 2-2d, 4-2c, 4-2d, 5b, 5c 및 5d를 합성하였다.합성한 화합물의 구조를 원소분석, $^1H$ NMR, mass spectral data로 확인하였으며, 합성한 화합물에 대한 항균 활성을 시험하였다. 利用市售鸟嘌呤合成了一系列具有生物活性的卤代嘌呤 (1)。鸟嘌呤与乙酸酐反应，通过乙酰化反应得到 2,9-二乙酰鸟嘌呤（2-1）。在 PEG-2000 相转移催化剂的作用下，2-1 与 $POCl_3$ 进一步处理，得到了重要的化合物 3a，然后在 TPPB 相转移催化剂的作用下，通过 KX 与 3a 之间的氯交换卤化反应，得到了 2-氨基-6-卤代嘌呤（3b-d）。在相应的 CuX 催化下，2-氨基-6-取代嘌呤（1、3a、4-1）通过重氮化反应有效地制备了 2-卤代嘌呤（2-2a-d、4-2a-d、5a-d），并发现了一些新化合物 2-2a、2-2c、2-2d、4-2c、4-2d、5b、5c 和 5d。合成化合物的结构主要是根据其元素分析、$^1H$核磁共振以及质谱数据确定的。对所有标题化合物进行了抗真菌活性筛选，其中一些化合物显示出良好的活性。
• The effect of the c-6 substituent on the regioselectivity of n-alkylation of 2-aminopurines
  作者：Graham R. Geen、Trevor J. Grinter、Peter M. Kincey、Richard L. Jarvest

  DOI：10.1016/s0040-4020(01)87878-9

  日期：1990.1
• MURAKAMI, KUNICHIKA;SHIRASAKA, TAKUMA;YOSHIOKA, HIDETOSHI;KOJIMA, EIJI;AO+, J. MED. CHEM., 34,(1991) N, C. 1606-1612
  作者：MURAKAMI, KUNICHIKA、SHIRASAKA, TAKUMA、YOSHIOKA, HIDETOSHI、KOJIMA, EIJI、AO+

  DOI：——

  日期：——
• Escherichia coli mediated biosynthesis and in vitro anti-HIV activity of lipophilic 6-halo-2',3'-dideoxypurine nucleosides
  作者：Kunichika Murakami、Takuma Shirasaka、Hidetoshi Yoshioka、Eiji Kojima、Shizuko Aoki、Harry Ford、John S. Driscoll、James A. Kelley、Hiroaki Mitsuya

  DOI：10.1021/jm00109a012

  日期：1991.5

  A series of 6-substituted 2',3'-dideoxypurine ribofuranosides (ddP) was enzymatically synthesized with live E. coli in an effort to enhance the lipophilicity of this class of anti-human immunodeficiency virus (HIV) compounds and thereby facilitate drug delivery into the central nervous system. All 6-halo-substituted ddPs were substantially more lipophilic, as defined by their octanol-water partition coefficient (P), than their nonhalogenated congeners 2',3'-dideoxyinosine (ddI) or 2',3'-dideoxyguanosine (ddG). For this class of compounds, log P's ranged from +0.5 to -1.2 in the following order: 6-iodo, 2-amino-6-iodo > 6-bromo, 2-amino-6-bromo > 6-chloro, 2-amino-6-chloro > 6-fluoro, 2-amino-6-fluoro >> ddG > ddI. These compounds were evaluated in vitro for ability to suppress the infectivity, replication, and cytopathic effect of HIV. 2-Amino-6-fluoro-, 2-amino-6-chloro-, and 6-fluoro-ddP exhibited a potent activity against HIV comparable to that of ddI or ddG and completely blocked the infectivity of HIV without affecting the growth of target cells. The comparative order of in vitro anti-HIV activity was 2-amino-6-fluoro, 2-amino-6-chloro, 6-fluoro > 2-amino-6-bromo > 2-amino-6-iodo, 6-chloro > 6-bromo > 6-iodo. These compounds also exhibited potent in vitro activity against HIV-2 and 3'-azido-3'-deoxythymidine-resistant HIV-1 variants. All 2-amino-6-halo-ddPs and 6-halo-ddPs were substrates for adenosine deaminase (ADA) and were converted to ddG or ddI, respectively. In the presence of the potent ADA inhibitor 2'-deoxycoformycin, 6-halo-substituted ddPs failed to exert an in vitro antiretroviral effect. These dideoxypurine nucleoside analogues represent a new class of lipophilic prodrugs of ddG and ddI that possess the potential for more effective therapy of HIV-induced neurologic disorders.
• 抗Ｂ型肝炎ウイルス剤
  申请人：ダイキン工業株式会社

  公开号：JP2020147532A

  公开（公告）日：2020-09-17

  【課題】核酸アナログを有効成分として含有する、抗Ｂ型肝炎ウイルス剤及びＢ型肝炎ウイルス関連疾患の予防又は治療剤を提供する。【解決手段】抗Ｂ型肝炎ウイルス剤及びＢ型肝炎ウイルス関連疾患の予防又は治療剤は、次式（１）：（式中、Ｒは、ハロゲン原子、アミノ基、メトキシ基、又はシアノ基である。）で表される化合物若しくはそのプロドラッグ、又はそれらの薬学的に許容される塩、或いはそれらの溶媒和物を有効成分として含有する。【選択図】なし

  提供含有核酸类似物作为有效成分的抗乙型肝炎病毒药物，以及用于预防或治疗乙型肝炎病毒相关疾病的药物。抗乙型肝炎病毒药物和乙型肝炎病毒相关疾病的预防或治疗药物包含以下式（1）所示的化合物或其前体（其中，R代表卤原子、氨基、甲氧基或氰基），或其药学上可接受的盐，或它们的溶剂物。【选择图】无