1-[[[[(3S,3aS,6aR)-Hexahydrofuro[2,3-b]furan-3-yl]oxy]carbonyl]oxy]-2,5-pyrrolidinedione | 799241-85-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃类
• 英文名称: 1-[[[[(3S,3aS,6aR)-Hexahydrofuro[2,3-b]furan-3-yl]oxy]carbonyl]oxy]-2,5-pyrrolidinedione
• 英文别名: [(3aS,4S,6aR)-2,3,3a,4,5,6a-hexahydrofuro[2,3-b]furan-4-yl] (2,5-dioxopyrrolidin-1-yl) carbonate
• CAS: 799241-85-3
• 化学式: C₁₁H₁₃NO₇
• 分子量: 271.227
• InChiKey: VCFNCYVHQSHFRH-NYNCVSEMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  91.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-[[[[(3S,3aS,6aR)-Hexahydrofuro[2,3-b]furan-3-yl]oxy]carbonyl]oxy]-2,5-pyrrolidinedione 、 4-氨基-N-[(2R, 3S)-3-氨基-2-羟基-4-苯丁基]-N-异丁基苯磺酰胺 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 darunavir
  参考文献：
  名称：

  Discovery and Selection of TMC114, a Next Generation HIV-1 Protease Inhibitor

  摘要：

  The screening of known HIV-1 protease inhibitors against a panel of multi-drug-resistant viruses revealed the potent activity of TMC126 on drug-resistant mutants. In comparison to amprenavir, the improved affinity of TMC126 is largely the result of one extra hydrogen bond to the backbone of the protein in the P2 pocket. Modification of the substitution pattern on the phenylsulfonamide P2 ' substituent of TMC126 created an interesting SAR, with the close analogue TMC114 being found to have a similar antiviral activity against the mutant and the wild-type viruses. X-ray and thermodynamic studies on both wild-type and mutant enzymes showed an extremely high enthalpy driven affinity of TMC114 for HIV-1 protease. In vitro selection of mutants resistant to TMC 114 starting from wild-type virus proved to be extremely difficult; this was not the case for other close analogues. Therefore, the extra H-bond to the backbone in the P2 pocket cannot be the only explanation for the interesting antiviral profile of TMC114. Absorption studies in animals indicated that TMC114 has pharmacokinetic properties comparable to currently approved HIV-1 protease inhibitors.

  DOI：

  10.1021/jm049560p
• 作为产物：
  描述：

  (3R,3AS,6AR)-六氢呋喃并[2,3-B]呋喃-3-醇 在 偶氮二甲酸二异丙酯 、 potassium carbonate 、 三乙胺 、 三苯基膦 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 生成 1-[[[[(3S,3aS,6aR)-Hexahydrofuro[2,3-b]furan-3-yl]oxy]carbonyl]oxy]-2,5-pyrrolidinedione
  参考文献：
  名称：

  Discovery and Selection of TMC114, a Next Generation HIV-1 Protease Inhibitor

  摘要：

  The screening of known HIV-1 protease inhibitors against a panel of multi-drug-resistant viruses revealed the potent activity of TMC126 on drug-resistant mutants. In comparison to amprenavir, the improved affinity of TMC126 is largely the result of one extra hydrogen bond to the backbone of the protein in the P2 pocket. Modification of the substitution pattern on the phenylsulfonamide P2 ' substituent of TMC126 created an interesting SAR, with the close analogue TMC114 being found to have a similar antiviral activity against the mutant and the wild-type viruses. X-ray and thermodynamic studies on both wild-type and mutant enzymes showed an extremely high enthalpy driven affinity of TMC114 for HIV-1 protease. In vitro selection of mutants resistant to TMC 114 starting from wild-type virus proved to be extremely difficult; this was not the case for other close analogues. Therefore, the extra H-bond to the backbone in the P2 pocket cannot be the only explanation for the interesting antiviral profile of TMC114. Absorption studies in animals indicated that TMC114 has pharmacokinetic properties comparable to currently approved HIV-1 protease inhibitors.

  DOI：

  10.1021/jm049560p
• 作为试剂：
  描述：

  、 N,N'-二琥珀酰亚胺基碳酸酯 、 三乙胺 、 乙酸乙酯 在 Brine 、 Sodium sulfate-III 、 1-[[[[(3S,3aS,6aR)-Hexahydrofuro[2,3-b]furan-3-yl]oxy]carbonyl]oxy]-2,5-pyrrolidinedione 作用下， 以 乙腈 为溶剂， 反应 24.0h， 以to provide crude compound 15, which的产率得到1-[[[[(3S,3aS,6aR)-Hexahydrofuro[2,3-b]furan-3-yl]oxy]carbonyl]oxy]-2,5-pyrrolidinedione
  参考文献：
  名称：

  HIV protease inhibitors

  摘要：

  本文披露了用于抑制HIV蛋白酶的化合物。本文还披露了制备这些化合物的方法以及它们作为治疗剂的用途，例如，用于治疗野生型HIV和多药耐药株的HIV。

  公开号：

  US07897635B2

文献信息

• Discovery and Selection of TMC114, a Next Generation HIV-1 Protease Inhibitor
  作者：Dominique L. N. G. Surleraux、Abdellah Tahri、Wim G. Verschueren、Geert M. E. Pille、Herman A. de Kock、Tim H. M. Jonckers、Anik Peeters、Sandra De Meyer、Hilde Azijn、Rudi Pauwels、Marie-Pierre de Bethune、Nancy M. King、Moses Prabu-Jeyabalan、Celia A. Schiffer、Piet B. T. P. Wigerinck

  DOI：10.1021/jm049560p

  日期：2005.3.1

  The screening of known HIV-1 protease inhibitors against a panel of multi-drug-resistant viruses revealed the potent activity of TMC126 on drug-resistant mutants. In comparison to amprenavir, the improved affinity of TMC126 is largely the result of one extra hydrogen bond to the backbone of the protein in the P2 pocket. Modification of the substitution pattern on the phenylsulfonamide P2 ' substituent of TMC126 created an interesting SAR, with the close analogue TMC114 being found to have a similar antiviral activity against the mutant and the wild-type viruses. X-ray and thermodynamic studies on both wild-type and mutant enzymes showed an extremely high enthalpy driven affinity of TMC114 for HIV-1 protease. In vitro selection of mutants resistant to TMC 114 starting from wild-type virus proved to be extremely difficult; this was not the case for other close analogues. Therefore, the extra H-bond to the backbone in the P2 pocket cannot be the only explanation for the interesting antiviral profile of TMC114. Absorption studies in animals indicated that TMC114 has pharmacokinetic properties comparable to currently approved HIV-1 protease inhibitors.
• HIV protease inhibitors
  申请人：——

  公开号：US20040039016A1

  公开（公告）日：2004-02-26

  Compounds useful for inhibiting HIV protease are disclosed. Methods of making the compounds, and their use as therapeutic agents, for example, in treating wild-type HIV and of multidrug-resistant strains of HIV, also are disclosed.

  本文披露了用于抑制HIV蛋白酶的化合物。同时，还披露了制备这些化合物的方法，以及它们作为治疗剂的用途，例如用于治疗野生型HIV和多药耐药株的HIV。