BISTHFHNS衍生物3 | 799241-86-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃类
• 中文名称: BISTHFHNS衍生物3
• 英文名称: 2,5-dioxopyrrolidin-1-yl ((3R,3aR,6aS)-hexahydrofuro[2,3-b]furan-3-yl) carbonate
• 英文别名: BIS THF HNS Derivative 3；[(3aR,4R,6aS)-2,3,3a,4,5,6a-hexahydrofuro[2,3-b]furan-4-yl] (2,5-dioxopyrrolidin-1-yl) carbonate
• CAS: 799241-86-4
• 化学式: C₁₁H₁₃NO₇
• 分子量: 271.227
• InChiKey: VCFNCYVHQSHFRH-FWWHASMVSA-N

物化性质

• 沸点：
  391.8±52.0 °C(Predicted)
• 密度：
  1.51±0.1 g/cm3(Predicted)

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：

  BISTHFHNS衍生物3 、 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：

  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 BISTHFHNS衍生物3
  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

文献信息

• 一种达卢那韦关键中间体的制备方法
  申请人：盐城迪赛诺制药有限公司

  公开号：CN114853774A

  公开（公告）日：2022-08-05

  本发明公开一种达卢那韦关键中间体的制备方法，属于医药技术领域。该方法是以式Ⅰ的化合物为原料，在四氢呋喃中经硼氢化锂还原生成式Ⅲ的化合物；再与式Ⅴ的化合物进行酯交换反应，制得式Ⅵ的化合物。本发明通过优化制备硼氢化锂的投料方式，使硼氢化锂提供氢负离子，进攻酯羰基，氯化锂和硼氢化钾分开加更利于反应生成硼氢化锂，氯化锂在四氢呋喃中以Li+更易游离与BH4‑结合能力强，缩短了反应时间，大大提高了生产效率，适用于商业化运用。