(3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl N-[(1S,2R)-3-((1,3-benzodioxol-5-ylsulfonyl)6-[(methoxycarbonyl)amino]-2,2-dimethylhexylamino)-1-benzyl-2-hydroxypropyl]carbamate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl N-[(1S,2R)-3-((1,3-benzodioxol-5-ylsulfonyl)6-[(methoxycarbonyl)amino]-2,2-dimethylhexylamino)-1-benzyl-2-hydroxypropyl]carbamate
• 英文别名: Methyl (6-{(1,3-benzodioxol-5-ylsulfonyl)[(2R,3S)-3-({[(3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yloxy]carbonyl}amino)-2-hydroxy-4-phenylbutyl]amino}-5,5-dimethylhexyl)carbamate；methyl N-[6-[[(2R,3S)-3-[[(3aS,4R,6aR)-2,3,3a,4,5,6a-hexahydrofuro[2,3-b]furan-4-yl]oxycarbonylamino]-2-hydroxy-4-phenylbutyl]-(1,3-benzodioxol-5-ylsulfonyl)amino]-5,5-dimethylhexyl]carbamate
• 化学式: C₃₄H₄₇N₃O₁₁S
• 分子量: 705.827
• InChiKey: KSQCICICDZVMLY-JIPUOCAHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  49
• 可旋转键数：
  18
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  180
• 氢给体数：
  3
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  2-(4-氯-1,1-二甲基丁基)-1,3-二氧戊环 在 镍 盐酸 、 4-二甲氨基吡啶 、 氨 、 氢气 、 三乙酰氧基硼氢化钠 、 溶剂黄146 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 70.0~100.0 ℃ 、275.79 kPa 条件下， 反应 22.5h， 生成 (3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl N-[(1S,2R)-3-((1,3-benzodioxol-5-ylsulfonyl)6-[(methoxycarbonyl)amino]-2,2-dimethylhexylamino)-1-benzyl-2-hydroxypropyl]carbamate
  参考文献：
  名称：

  Novel arylsulfonamides possessing sub-picomolar HIV protease activities and potent anti-HIV activity against wild-type and drug-resistant viral strains

  摘要：

  A novel series of P1' chain-extended arylsufonamides was synthesiszed and evaluated for wild-type HIV protease inhibitory activity and in vitro antiviral activity against wild type virus and two protease inhibitor-resistant mutant viruses. All of the compounds showed dramatic increases in enzyme activity as compared to the currently marketed HIV protease inhibitors amprenavir, indinavir, and nelfinavir. In addition, significant improvements in antiviral potencies against wild type and the two mutant viruses were also realized. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.12.008

文献信息

• Inhibitors of aspartyl protease
  申请人：Vertex Pharmaceuticals Incorporated

  公开号：US06319946B1

  公开（公告）日：2001-11-20

  The present invention relates to a novel class of sulfonamides which are aspartyl protease inhibitors. In one embodiment, this invention relates to a novel class of HIV aspartyl protease inhibitors characterized by specific structural and physicochemical features. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting HIV-1 and HIV-2 protease activity and consequently, may be advantageously used as anti-viral agents against the HIV-1 and HIV-2 viruses. This invention also relates to methods for inhibiting the activity of HIV aspartyl protease using the compounds of this invention and methods for screening compounds for anti-HIV activity.

  本发明涉及一类新型的磺胺类化合物，它们是天冬氨酸蛋白酶抑制剂。在一个实施例中，本发明涉及一类新型的HIV天冬氨酸蛋白酶抑制剂，其具有特定的结构和理化特征。本发明还涉及包含这些化合物的药物组合物。本发明的化合物和药物组合物特别适用于抑制HIV-1和HIV-2蛋白酶活性，因此，可以有益地用作抗HIV-1和HIV-2病毒的抗病毒剂。本发明还涉及使用本发明的化合物抑制HIV天冬氨酸蛋白酶活性的方法以及筛选具有抗HIV活性的化合物的方法。
• US6319946B1
  申请人：——

  公开号：US6319946B1

  公开（公告）日：2001-11-20
• US7442718B2
  申请人：——

  公开号：US7442718B2

  公开（公告）日：2008-10-28
• US7919523B2
  申请人：——

  公开号：US7919523B2

  公开（公告）日：2011-04-05
• Novel arylsulfonamides possessing sub-picomolar HIV protease activities and potent anti-HIV activity against wild-type and drug-resistant viral strains
  作者：John F. Miller、Eric S. Furfine、Mary H. Hanlon、Richard J. Hazen、John A. Ray、Laurence Robinson、Vicente Samano、Andrew Spaltenstein

  DOI：10.1016/j.bmcl.2003.12.008

  日期：2004.2

  A novel series of P1' chain-extended arylsufonamides was synthesiszed and evaluated for wild-type HIV protease inhibitory activity and in vitro antiviral activity against wild type virus and two protease inhibitor-resistant mutant viruses. All of the compounds showed dramatic increases in enzyme activity as compared to the currently marketed HIV protease inhibitors amprenavir, indinavir, and nelfinavir. In addition, significant improvements in antiviral potencies against wild type and the two mutant viruses were also realized. (C) 2003 Elsevier Ltd. All rights reserved.