N-(9-{(2R,4S,5R)-5-[Bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-4-[(2R,3S,5R)-3-hydroxy-5-(4-hydroxy-5-methyl-2-oxo-2H-pyrimidin-1-yl)-tetrahydro-furan-2-ylmethoxymethoxy]-tetrahydro-furan-2-yl}-6-oxo-6,9-dihydro-1H-purin-2-yl)-isobutyramide | 215248-62-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: N-(9-{(2R,4S,5R)-5-[Bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-4-[(2R,3S,5R)-3-hydroxy-5-(4-hydroxy-5-methyl-2-oxo-2H-pyrimidin-1-yl)-tetrahydro-furan-2-ylmethoxymethoxy]-tetrahydro-furan-2-yl}-6-oxo-6,9-dihydro-1H-purin-2-yl)-isobutyramide
• 英文别名: N-[9-[(2R,4S,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-[[(2R,3S,5R)-3-hydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxymethoxy]oxolan-2-yl]-6-oxo-1H-purin-2-yl]-2-methylpropanamide
• CAS: 215248-62-7
• 化学式: C₄₆H₅₁N₇O₁₂
• 分子量: 893.951
• InChiKey: PLRZYQBKDOGNFB-CXPJILFNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  65
• 可旋转键数：
  17
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  223
• 氢给体数：
  4
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  2-氰乙基N,N-二异丙基氯亚磷酰胺 、 N-(9-{(2R,4S,5R)-5-[Bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-4-[(2R,3S,5R)-3-hydroxy-5-(4-hydroxy-5-methyl-2-oxo-2H-pyrimidin-1-yl)-tetrahydro-furan-2-ylmethoxymethoxy]-tetrahydro-furan-2-yl}-6-oxo-6,9-dihydro-1H-purin-2-yl)-isobutyramide 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 以18%的产率得到N-[9-[(2R,4S,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-[[(2R,3S,5R)-3-[2-cyanoethoxy-[di(propan-2-yl)amino]phosphanyl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxymethoxy]oxolan-2-yl]-6-oxo-1H-purin-2-yl]-2-methylpropanamide
  参考文献：
  名称：

  In Vitro and in Vivo Activities of Oligodeoxynucleotide-Based Thrombin Inhibitors Containing Neutral Formacetal Linkages

  摘要：

  A series of 15-mer oligodeoxynucleotide analogues were synthesized, and their thrombin inhibitory activities in vitro and in vivo were evaluated. These oligodeoxynucleotide analogues share the same sequence (GGTTGGTGTGGTTGG) but have one or more phosphodiester linkages replaced by a neutral formacetal group. The results obtained from monosubstitutions show that no single phosphodiester group is critical for the thrombin inhibitory activity, suggesting that the interaction between the oligodeoxynucleotide and thrombin is based on a multiple-site charge-charge interaction. Analysis of the effects of different phosphodiester replacements indicates that the backside and left side of the chairlike structure formed by the molecule may be involved in binding with thrombin, presumably by having direct contacts with the anion-binding exosite of the enzyme. For the oligodeoxynucleotides containing two noncontiguous formacetal groups, the effect of the disubstitution is the sum of the effects obtained from the corresponding two monosubstitutions. Infusion of an oligodeoxynucleotide containing four formacetal groups into monkeys showed an increased in vivo anticoagulant effect and an extended in vivo half-life compared to the unmodified oligodeoxynucleotide.

  DOI：

  10.1021/jm970766i
• 作为产物：
  描述：

  Benzoic acid (2R,3S,5R)-5-(2-isobutyrylamino-6-oxo-1,6-dihydro-purin-9-yl)-3-methylsulfanylmethoxy-tetrahydro-furan-2-ylmethyl ester 在 吡啶 、 氢氧化钾 、 N-碘代丁二酰亚胺 、 三氟甲磺酸三甲基硅酯 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醚 、 二氯甲烷 为溶剂， 反应 1.5h， 生成 N-(9-{(2R,4S,5R)-5-[Bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-4-[(2R,3S,5R)-3-hydroxy-5-(4-hydroxy-5-methyl-2-oxo-2H-pyrimidin-1-yl)-tetrahydro-furan-2-ylmethoxymethoxy]-tetrahydro-furan-2-yl}-6-oxo-6,9-dihydro-1H-purin-2-yl)-isobutyramide
  参考文献：
  名称：

  In Vitro and in Vivo Activities of Oligodeoxynucleotide-Based Thrombin Inhibitors Containing Neutral Formacetal Linkages

  摘要：

  A series of 15-mer oligodeoxynucleotide analogues were synthesized, and their thrombin inhibitory activities in vitro and in vivo were evaluated. These oligodeoxynucleotide analogues share the same sequence (GGTTGGTGTGGTTGG) but have one or more phosphodiester linkages replaced by a neutral formacetal group. The results obtained from monosubstitutions show that no single phosphodiester group is critical for the thrombin inhibitory activity, suggesting that the interaction between the oligodeoxynucleotide and thrombin is based on a multiple-site charge-charge interaction. Analysis of the effects of different phosphodiester replacements indicates that the backside and left side of the chairlike structure formed by the molecule may be involved in binding with thrombin, presumably by having direct contacts with the anion-binding exosite of the enzyme. For the oligodeoxynucleotides containing two noncontiguous formacetal groups, the effect of the disubstitution is the sum of the effects obtained from the corresponding two monosubstitutions. Infusion of an oligodeoxynucleotide containing four formacetal groups into monkeys showed an increased in vivo anticoagulant effect and an extended in vivo half-life compared to the unmodified oligodeoxynucleotide.

  DOI：

  10.1021/jm970766i

文献信息

• In Vitro and in Vivo Activities of Oligodeoxynucleotide-Based Thrombin Inhibitors Containing Neutral Formacetal Linkages
  作者：Gong-Xin He、John P. Williams、Michael J. Postich、S. Swaminathan、Regan G. Shea、Terry Terhorst、Veronica S. Law、Cheri T. Mao、Cathy Sueoka、Steven Coutré、Norbert Bischofberger

  DOI：10.1021/jm970766i

  日期：1998.10.1

  A series of 15-mer oligodeoxynucleotide analogues were synthesized, and their thrombin inhibitory activities in vitro and in vivo were evaluated. These oligodeoxynucleotide analogues share the same sequence (GGTTGGTGTGGTTGG) but have one or more phosphodiester linkages replaced by a neutral formacetal group. The results obtained from monosubstitutions show that no single phosphodiester group is critical for the thrombin inhibitory activity, suggesting that the interaction between the oligodeoxynucleotide and thrombin is based on a multiple-site charge-charge interaction. Analysis of the effects of different phosphodiester replacements indicates that the backside and left side of the chairlike structure formed by the molecule may be involved in binding with thrombin, presumably by having direct contacts with the anion-binding exosite of the enzyme. For the oligodeoxynucleotides containing two noncontiguous formacetal groups, the effect of the disubstitution is the sum of the effects obtained from the corresponding two monosubstitutions. Infusion of an oligodeoxynucleotide containing four formacetal groups into monkeys showed an increased in vivo anticoagulant effect and an extended in vivo half-life compared to the unmodified oligodeoxynucleotide.