(2'R,5'R)-1-(5-phosphonylmethoxy-2,5-dihydrofuran-2-yl)thymine | 733711-56-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: (2'R,5'R)-1-(5-phosphonylmethoxy-2,5-dihydrofuran-2-yl)thymine
• 英文别名: [(2R,5R)-5-(5-methyl-2,4-dioxo-pyrimidin-1-yl)-2,5-dihydrofuran-2-yl]oxymethylphosphonic acid；[(2R,5R)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)-2,5-dihydrofuran-2-yl]oxymethylphosphonic acid
• CAS: 733711-56-3
• 化学式: C₁₀H₁₃N₂O₇P
• 分子量: 304.196
• InChiKey: GFOIEUKLMHXAEP-SFYZADRCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.9
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  125
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2'R,5'R)-1-(5-phosphonylmethoxy-2,5-dihydrofuran-2-yl)thymine 在 N,N'-羰基二咪唑 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 以39%的产率得到(β,γ-imido)diphosphoryl-(2'R,5'R)-1-(5-phosphonylmethoxy-2,5-dihydrofuran-2-yl)thymine
  参考文献：
  名称：

  Isosteric triphosphonate analogues of dNTP: Synthesis and substrate properties toward various DNA polymerases

  摘要：

  Isosteric triphosphonate derivatives of 2',3'-dideoxy-2',3'-didehydroadenosine and 3'-deoxy-2',3'-didehydrothymidine and their beta,gamma-substituted analogues were synthesized. Their substrate properties toward a number of reverse transcriptases of the human immunodeficiency and avian myeloblastosis viruses, human DNA polymerases alpha and beta, and the Klenow fragment of Escherichia coli DNA polymerase I were studied.

  DOI：

  10.1134/s1068162007050056
• 作为产物：
  描述：

  (2'R,3'S,5'R)-1-(2-diethoxyphosphinoylmethoxy-3-iodotetrahydrofuran-5-yl)thymine 在 三甲基溴硅烷 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 N,N-二甲基甲酰胺 、 四氢呋喃 为溶剂， 反应 27.5h， 以70%的产率得到(2'R,5'R)-1-(5-phosphonylmethoxy-2,5-dihydrofuran-2-yl)thymine
  参考文献：
  名称：

  Isosteric triphosphonate analogues of dNTP: Synthesis and substrate properties toward various DNA polymerases

  摘要：

  Isosteric triphosphonate derivatives of 2',3'-dideoxy-2',3'-didehydroadenosine and 3'-deoxy-2',3'-didehydrothymidine and their beta,gamma-substituted analogues were synthesized. Their substrate properties toward a number of reverse transcriptases of the human immunodeficiency and avian myeloblastosis viruses, human DNA polymerases alpha and beta, and the Klenow fragment of Escherichia coli DNA polymerase I were studied.

  DOI：

  10.1134/s1068162007050056

文献信息

• Synthesis, anti-HIV activity, and resistance profile of thymidine phosphonomethoxy nucleosides and their bis-isopropyloxymethylcarbonyl (bisPOC) prodrugs
  作者：Richard L. Mackman、Lijun Zhang、Vidya Prasad、Constantine G. Boojamra、Janet Douglas、Deborah Grant、Hon Hui、Choung U. Kim、Genevieve Laflamme、Jay Parrish、Antitsa D. Stoycheva、Swami Swaminathan、KeYu Wang、Tomas Cihlar

  DOI：10.1016/j.bmc.2007.05.047

  日期：2007.8

  (NRTIs), 3'-azido-2',3'-dideoxythymidine (AZT), 2',3'-didehydro-2',3'-dideoxythymidine (d4T), and 2',3'-dideoxythymidine (ddT), were synthesized. The anti-HIV activity against wild-type and several major nucleoside-resistant strains of HIV-1 was evaluated together with the inhibition of wild-type HIV reverse transcriptase (RT). Phosphonomethoxy analog of d4T, 8 (d4TP), demonstrated antiviral activity with

  含胸腺嘧啶核苷逆转录酶抑制剂（NRTIs），3'-叠氮基2'，3'-二脱氧胸苷（AZT），2'，3'-二脱氢-2'，3'-二脱氧胸苷（d4T）的膦甲氧基核苷类似物，合成2'，3'-二脱氧胸苷（ddT）。与野生型HIV逆转录酶（RT）的抑制作用一起评估了抗HIV-1对野生型和几种主要的抗核苷主要毒株的抗HIV活性。d4T，8（d4TP）的膦氧甲氧基类似物表现出抗病毒活性，其EC（50）值为26 microM，而ddT，7（ddTP）和AZT，6（AZTP）的膦酰甲氧基类似物在浓度升高时均无活性到200 microM。双异丙氧基甲氧羰基（bisPOC）前药分别将7和8的抗HIV活性提高了150倍和29倍，从而确定抗病毒耐药性。与bisPOC PMPA（替诺福韦DF）1相比，K65R RT突变病毒对bisPOC前药7和8的耐药性更高。但是，bisPOC前药7对含有多个胸苷类似物突变（6TAMs）
• Synthesis, anti-HIV activity, and resistance profiles of ribose modified nucleoside phosphonates
  作者：Richard L. Mackman、Constantine G. Boojamra、Vidya Prasad、Lijun Zhang、Kuei-Ying Lin、Oleg Petrakovsky、Darius Babusis、James Chen、Janet Douglas、Deborah Grant、Hon C. Hui、Choung U. Kim、David Y. Markevitch、Jennifer Vela、Adrian Ray、Tomas Cihlar

  DOI：10.1016/j.bmcl.2007.10.038

  日期：2007.12

  A series of nucleoside phosphonate reverse transcriptase (RT) inhibitors have been synthesized and their anti-HIV activity and resistance profiles evaluated. The most potent analog [5-(6-amino-purin-9-yl)-2,5-dihydro-furan-2-yloxymethyl]-phosphonic acid (d4AP) demonstrated a HIV EC50 = 2.1 mu M, and the most favorable resistance profile against HIV-1 variants with K65R, M184V or multiple thymidine analog mutations in RT. (c) 2007 Elsevier Ltd. All rights reserved.