9-(5',6'-dideoxy-6'-phosphono-β-D-ribo-hexofuranosyl)adenine | 22257-15-4

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 5'-脱氧核糖核苷
• 英文名称: 9-(5',6'-dideoxy-6'-phosphono-β-D-ribo-hexofuranosyl)adenine
• 英文别名: ACP；2-[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]ethylphosphonic acid
• CAS: 22257-15-4
• 化学式: C₁₁H₁₆N₅O₆P
• 分子量: 345.252
• InChiKey: ZUNJAJMPPKRIGU-IOSLPCCCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.4
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  177
• 氢给体数：
  5
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  9-(5',6'-dideoxy-6'-phosphono-β-D-ribo-hexofuranosyl)adenine 在 吡啶 、 氨 作用下， 生成 {2-[(2R,3S,4R,5R)-5-(6-Amino-purin-9-yl)-3,4-dihydroxy-tetrahydro-furan-2-yl]-ethyl}-phosphonic acid; compound with ammonia
  参考文献：
  名称：

  Mikhailov, Sergei N.; Padyukova, Nelly Sh.; Karpeiskii, Marat Ya., Collection of Czechoslovak Chemical Communications, 1989, vol. 54, # 4, p. 1055 - 1066

  摘要：

  DOI：
• 作为产物：
  描述：

  [(2R,3R,4R,5S)-4,5-diacetyloxy-2-(2-diethoxyphosphorylethyl)oxolan-3-yl] benzoate 在 甲醇 、 三甲基溴硅烷 、 氨 、 四氯化锡 作用下， 以 1,2-二氯乙烷 为溶剂， 生成 9-(5',6'-dideoxy-6'-phosphono-β-D-ribo-hexofuranosyl)adenine
  参考文献：
  名称：

  5'-核苷酸膦酸酯类似物合成的新方案

  摘要：

  提出了一种方便且通用的方法，以5-脱氧-1,2-O-异亚丙基-α-D-木糖六呋喃糖为原料合成5'-核苷酸膦酸酯类似物（1）。

  DOI：

  10.1016/s0040-4039(00)95552-7

文献信息

• Thiazole-4-carboxamide adenine dinucleotide (TAD). Analogs stable to phosphodiesterase hydrolysis
  作者：Victor E. Marquez、Christopher K. H. Tseng、Gulilat Gebeyehu、David A. Cooney、Gurpreet S. Ahluwalia、James A. Kelley、Maha Dalal、Richard W. Fuller、Yvonne A. Wilson、David G. Johns

  DOI：10.1021/jm00159a027

  日期：1986.9

  Thiazole-4-carboxamide adenine dinucleotide (TAD), the active metabolite of the oncolytic C-nucleoside tiazofurin (TR), is susceptible to phosphodiesteratic breakdown by a unique phosphodiesterase present at high levels in TR-resistant tumors. Since accumulation of TAD, as regulated by its synthetic and degradative enzymes, appears to be an important determinant for sensitivity to the drug, a series of hydrolytically resistant phosphonate analogues of TAD were synthesized with the intent of producing more stable compounds with an ability to inhibit IMP dehydrogenase equivalent to TAD itself. Isosteric phosphonic acid analogues of TR and adenosine nucleotides were coupled with activated forms of AMP and TR monophosphate to give dinucleotides 2 and 4. Coupling of protected adenosine 5'-(alpha, beta-methylene)diphosphate with isopropylidene-TR in the presence of DCC afforded compound 3 after deprotection. These compounds are more resistant than TAD toward hydrolysis and still retain potent activity against IMP dehydrogenase in vitro. beta-Methylene-TAD (3), the most stable of the TAD phosphonate analogues, produced a depletion of guanine nucleotide pools in an experimentally induced TR-resistant P388 tumor variant that was superior to that obtained with TR in the corresponding sensitive line.
• Design, Synthesis, and Antiviral Activity of Adenosine 5‘-Phosphonate Analogues as Chain Terminators against Hepatitis C Virus
  作者：Yung-hyo Koh、Jae Hoon Shim、Jim Zhen Wu、Weidong Zhong、Zhi Hong、Jean-Luc Girardet

  DOI：10.1021/jm049029u

  日期：2005.4.1

  A series of adenosine 5'-phosphonate analogues were designed to mimic naturally occurring adenosine monophosphate. These compounds (1-5) were synthesized and evaluated in a cellular hepatitis C virus (HCV) replication assay. To improve cellular permeability and enhance the anti-HCV activity of these phosphonates, a bis(S-acyl-2-thioethyl) prodrug for compound 5 was prepared, and its cellular activity was determined. To elucidate the mechanism of action of these novel adenosine phosphonates, their diphosphate derivatives (1a-5a) were synthesized. Further nucleotide incorporation assays by HCV NS5B RNA-dependent RNA polymerase revealed that 2a and 3a can serve as chain terminators, whereas compounds 1a, 4a, and 5a are competitive inhibitors with ATP. Additional steady-state kinetic analysis determined the incorporation efficiency of 2a and 3a as well as the inhibition constants for 1a, 4a, and 5a. The structure -activity relationships among these compounds were analyzed, and the implication for nucleoside phosphonate drug design was discussed.
• Hollmann, Juergen; Schlimme, Eckhard, Liebigs Annalen der Chemie, 1984, # 1, p. 98 - 107
  作者：Hollmann, Juergen、Schlimme, Eckhard

  DOI：——

  日期：——
• Moriguchi, Tomohisa; Yanagi, Terukazu; Wada, Takeshi, Journal of the Chemical Society. Perkin transactions I, 1999, # 13, p. 1859 - 1865
  作者：Moriguchi, Tomohisa、Yanagi, Terukazu、Wada, Takeshi、Sekine, Mitsuo

  DOI：——

  日期：——
• PADYUKOVA, N. SH.;KARPEISKY, M. YA.;KOLOBUSHKINA, L. I.;MIKHAILOV, S. N., TETRAHEDRON LETT., 28,(1987) N 31, 3623-3626
  作者：PADYUKOVA, N. SH.、KARPEISKY, M. YA.、KOLOBUSHKINA, L. I.、MIKHAILOV, S. N.

  DOI：——

  日期：——