5-hydroxy-3'-fluoro-2',3'-dideoxyuridine | 1258493-98-9

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 5-hydroxy-3'-fluoro-2',3'-dideoxyuridine
• 英文别名: 1-[(2R,4S,5R)-4-fluoro-5-(hydroxymethyl)tetrahydrofuran-2-yl]-5-hydroxy-pyrimidine-2,4-dione；1-[(2R,4S,5R)-4-fluoro-5-(hydroxymethyl)oxolan-2-yl]-5-hydroxypyrimidine-2,4-dione
• CAS: 1258493-98-9
• 化学式: C₉H₁₁FN₂O₅
• 分子量: 246.195
• InChiKey: WFVQBSJAFMHYEB-UBKIQSJTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  99.1
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-hydroxy-3'-fluoro-2',3'-dideoxyuridine 、 3-溴丙炔 在 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 12.0h， 以19%的产率得到5-(2-propynyloxy)-3-N-(2-propynyl)-3'-fluoro-2',3'-dideoxyuridine
  参考文献：
  名称：

  C-5炔基（炔氧基或羟甲基）和/或N-3丙炔基取代的嘧啶核苷类似物作为新型抗菌剂的研究

  摘要：

  分支杆菌感染的复发和耐药菌株的出现迫切需要一类不同于当前疗法的新型药物。A组5-乙炔基（的6 - 10），5-（2-丙炔氧基）（16，18，20，22，24），5-（2-丙炔氧基）-3- ñ - （2-丙炔基）（17，19，21，23，25）和5-羟甲基-3- ñ - （2-丙炔基）（30 - 33）的嘧啶核苷衍生物的合成和对分枝杆菌[评价结核分枝杆菌（Mtb），牛分枝杆菌（BCG）和鸟分枝杆菌），革兰氏阳性菌（金黄色葡萄球菌和粪肠球菌）和革兰氏阴性菌（大肠杆菌，鼠伤寒沙门氏菌和铜绿假单胞菌与单独的药物合用）体外测定。尽管几种化合物在较高浓度下对Mtb，牛分枝杆菌，金黄色葡萄球菌和粪肠球菌均表现出明显的抑制活性。，它们在较低的浓度下与抗结核药异烟肼和利福平以及抗菌药庆大霉素具有出乎意料的协同作用和加性相互作用。还发现了活性类似物在感染了H37Ra的人单核细胞系中抑制细胞内Mtb。5-羟甲基-3-口服给药ñ

  DOI：

  10.1016/j.bmc.2016.09.008
• 作为产物：
  描述：

  3′-氟-2′,3′-二脱氧尿苷 在 水 、 溴 、 吡啶 作用下， 以 水 为溶剂， 以37%的产率得到5-hydroxy-3'-fluoro-2',3'-dideoxyuridine
  参考文献：
  名称：

  Synthesis and in vitro antiviral activities of 3′-fluoro (or chloro) and 2′,3′-difluoro 2′,3′-dideoxynucleoside analogs against hepatitis B and C viruses

  摘要：

  Chronic infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) lead to serious liver diseases worldwide. Co-infection with HBV and HCV is very common and is associated with increased risk of liver pathogenesis, liver cancer, and liver failure. Several 5-substituted 3'-fluoro (or chloro) (1-4, 6, 7, 17-19) and 2',3'-difluoro 2',3'-dideoxynucleosides (15 and 16) were synthesized and evaluated for in vitro antiviral activities against duck hepatitis B virus (DHBV), human hepatitis B virus, and hepatitis C virus. Of these compounds 4, 7, 17, and 19 demonstrated moderate anti-HBV activity, and 2, 4, 7, 8, and 19 were weak inhibitors of HCV. Although 5-iodo derivative (7) was most inhibitory against HCV, it exhibited a reduction in cellular RNA levels in Huh-7 cells. The 5-hydroxymethyl-3'-fluoro-2',3'-dideoxyuridine (4) and 1-(3-chloro-2,3-dideoxy-beta-D-erythro-pentofuranosyl)-5-fluorouracil (19) provided the most inhibition of both viruses without cytotoxicity. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.08.048

文献信息

• Investigation of C-5 alkynyl (alkynyloxy or hydroxymethyl) and/or N-3 propynyl substituted pyrimidine nucleoside analogs as a new class of antimicrobial agents
  作者：Saurabh Garg、Neeraj Shakya、Naveen C. Srivastav、Babita Agrawal、Dennis Y. Kunimoto、Rakesh Kumar

  DOI：10.1016/j.bmc.2016.09.008

  日期：2016.11

  infections and the emergence of drug-resistant strains urgently require a new class of agents that are distinct than current therapies. A group of 5-ethynyl (6–10), 5-(2-propynyloxy) (16, 18, 20, 22, 24), 5-(2-propynyloxy)-3-N-(2-propynyl) (17, 19, 21, 23, 25) and 5-hydroxymethyl-3-N-(2-propynyl) (30–33) derivatives of pyrimidine nucleosides were synthesized and evaluated against mycobacteria [Mycobacterium

  分支杆菌感染的复发和耐药菌株的出现迫切需要一类不同于当前疗法的新型药物。A组5-乙炔基（的6 - 10），5-（2-丙炔氧基）（16，18，20，22，24），5-（2-丙炔氧基）-3- ñ - （2-丙炔基）（17，19，21，23，25）和5-羟甲基-3- ñ - （2-丙炔基）（30 - 33）的嘧啶核苷衍生物的合成和对分枝杆菌[评价结核分枝杆菌（Mtb），牛分枝杆菌（BCG）和鸟分枝杆菌），革兰氏阳性菌（金黄色葡萄球菌和粪肠球菌）和革兰氏阴性菌（大肠杆菌，鼠伤寒沙门氏菌和铜绿假单胞菌与单独的药物合用）体外测定。尽管几种化合物在较高浓度下对Mtb，牛分枝杆菌，金黄色葡萄球菌和粪肠球菌均表现出明显的抑制活性。，它们在较低的浓度下与抗结核药异烟肼和利福平以及抗菌药庆大霉素具有出乎意料的协同作用和加性相互作用。还发现了活性类似物在感染了H37Ra的人单核细胞系中抑制细胞内Mtb。5-羟甲基-3-口服给药ñ
• Synthesis and in vitro antiviral activities of 3′-fluoro (or chloro) and 2′,3′-difluoro 2′,3′-dideoxynucleoside analogs against hepatitis B and C viruses
  作者：Naveen C. Srivastav、Neeraj Shakya、Michelle Mak、Chao Liang、D. Lorne J. Tyrrell、Babita Agrawal、Rakesh Kumar

  DOI：10.1016/j.bmc.2010.08.048

  日期：2010.11

  Chronic infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) lead to serious liver diseases worldwide. Co-infection with HBV and HCV is very common and is associated with increased risk of liver pathogenesis, liver cancer, and liver failure. Several 5-substituted 3'-fluoro (or chloro) (1-4, 6, 7, 17-19) and 2',3'-difluoro 2',3'-dideoxynucleosides (15 and 16) were synthesized and evaluated for in vitro antiviral activities against duck hepatitis B virus (DHBV), human hepatitis B virus, and hepatitis C virus. Of these compounds 4, 7, 17, and 19 demonstrated moderate anti-HBV activity, and 2, 4, 7, 8, and 19 were weak inhibitors of HCV. Although 5-iodo derivative (7) was most inhibitory against HCV, it exhibited a reduction in cellular RNA levels in Huh-7 cells. The 5-hydroxymethyl-3'-fluoro-2',3'-dideoxyuridine (4) and 1-(3-chloro-2,3-dideoxy-beta-D-erythro-pentofuranosyl)-5-fluorouracil (19) provided the most inhibition of both viruses without cytotoxicity. (C) 2010 Elsevier Ltd. All rights reserved.