2,6-dichloro-9-(2,3-dideoxy-β-D-glycero-pentofuranosyl)-9H-purine | 132194-27-5

• 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: 2,6-dichloro-9-(2,3-dideoxy-β-D-glycero-pentofuranosyl)-9H-purine
• 英文别名: 2,6-Dichloro-9-(2,3-dideoxy-beta-D-glycero-pentofuranosyl)-9H-purine；[(2S,5R)-5-(2,6-dichloropurin-9-yl)oxolan-2-yl]methanol
• CAS: 132194-27-5
• 化学式: C₁₀H₁₀Cl₂N₄O₂
• 分子量: 289.121
• InChiKey: RGYWJHROUWPNRP-NTSWFWBYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  18
• 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：
  73.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2,6-二氯嘌呤 、 2',3'-二脱氧尿苷 反应 3.0h， 以9.7%的产率得到2,6-dichloro-9-(2,3-dideoxy-β-D-glycero-pentofuranosyl)-9H-purine
  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

文献信息

• 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：——
• PURINE DERIVATIVES AS CD73 INHIBITORS FOR THE TREATMENT OF CANCER
  申请人：Boehringer Ingelheim International GmbH

  公开号：EP3134411B1

  公开（公告）日：2021-06-30
• 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.