N-(3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl-oxycarbonyl-(4S,5R)-4-[4-(3-cyanobenzyloxy)-benzyl]-5-i-butyl-[(3,4-methylenedioxyphenyl)sulfonyl]-aminomethyl-2,2-dimethyl-oxazolidine | 313682-05-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: N-(3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl-oxycarbonyl-(4S,5R)-4-[4-(3-cyanobenzyloxy)-benzyl]-5-i-butyl-[(3,4-methylenedioxyphenyl)sulfonyl]-aminomethyl-2,2-dimethyl-oxazolidine
• 英文别名: [(3aS,4R,6aR)-2,3,3a,4,5,6a-hexahydrofuro[2,3-b]furan-4-yl] (4S,5R)-5-[[1,3-benzodioxol-5-ylsulfonyl(2-methylpropyl)amino]methyl]-4-[[4-[(3-cyanophenyl)methoxy]phenyl]methyl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylate
• CAS: 313682-05-2
• 化学式: C₃₉H₄₅N₃O₁₀S
• 分子量: 747.866
• InChiKey: CFFSKKINERTPCV-NCTMPQFNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  53
• 可旋转键数：
  13
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.49
• 拓扑面积：
  155
• 氢给体数：
  0
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  N-(3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl-oxycarbonyl-(4S,5R)-4-[4-(3-cyanobenzyloxy)-benzyl]-5-i-butyl-[(3,4-methylenedioxyphenyl)sulfonyl]-aminomethyl-2,2-dimethyl-oxazolidine 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 生成 (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl-N((1S,2R)-1-[4-(3-cyanobenzyloxy)-benzyl]-3-i-butyl-[(3,4-methylenedioxyphenyl)sulfonyl]-amino-2-hydroxypropyl)-carbamate
  参考文献：
  名称：

  Ultra-potent P1 modified arylsulfonamide HIV protease inhibitors: The discovery of GW0385

  摘要：

  A novel series of P1 modified HIV protease inhibitors was synthesized and evaluated for in vitro antiviral activity against wild-type virus and protease inhibitor-resistant viruses. Optimization of the P1 moiety resulted in compounds with femtomolar enzyme activities and cellular antiviral activities in the low nanomolar range culminating in the identification of clinical candidate GW0385. (C) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.01.035
• 作为产物：
  描述：

  N-(3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl-oxycarbonyl-, (4S,5R)-4-(4-benzyloxy-benzyl)-5-i-butyl-[(3,4-methylenedioxyphenyl)sulfonyl]-aminomethyl-2,2-dimethyl-oxazolidine 在 palladium on activated charcoal 氢气 、 caesium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-(3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl-oxycarbonyl-(4S,5R)-4-[4-(3-cyanobenzyloxy)-benzyl]-5-i-butyl-[(3,4-methylenedioxyphenyl)sulfonyl]-aminomethyl-2,2-dimethyl-oxazolidine
  参考文献：
  名称：

  Ultra-potent P1 modified arylsulfonamide HIV protease inhibitors: The discovery of GW0385

  摘要：

  A novel series of P1 modified HIV protease inhibitors was synthesized and evaluated for in vitro antiviral activity against wild-type virus and protease inhibitor-resistant viruses. Optimization of the P1 moiety resulted in compounds with femtomolar enzyme activities and cellular antiviral activities in the low nanomolar range culminating in the identification of clinical candidate GW0385. (C) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.01.035

文献信息

• INHIBITORS OF ASPARTYL PROTEASE
  申请人：Hale Michael R.

  公开号：US20090274650A1

  公开（公告）日：2009-11-05

  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.

  本发明涉及一种新的磺胺类化合物，它们是天冬氨酸蛋白酶抑制剂。在一种实施例中，本发明涉及一种新的HIV天冬氨酸蛋白酶抑制剂，其具有特定的结构和物理化学特征。本发明还涉及包含这些化合物的制药组合物。本发明的化合物和制药组合物特别适用于抑制HIV-1和HIV-2蛋白酶活性，因此，可以优势地用作抗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。
• US8455497B2
  申请人：——

  公开号：US8455497B2

  公开（公告）日：2013-06-04
• Ultra-potent P1 modified arylsulfonamide HIV protease inhibitors: The discovery of GW0385
  作者：John F. Miller、C. Webster Andrews、Michael Brieger、Eric S. Furfine、Michael R. Hale、Mary H. Hanlon、Richard J. Hazen、Istvan Kaldor、Ed W. McLean、David Reynolds、Douglas M. Sammond、Andrew Spaltenstein、Roger Tung、Elizabeth M. Turner、Robert X. Xu、Ronald G. Sherrill

  DOI：10.1016/j.bmcl.2006.01.035

  日期：2006.4

  A novel series of P1 modified HIV protease inhibitors was synthesized and evaluated for in vitro antiviral activity against wild-type virus and protease inhibitor-resistant viruses. Optimization of the P1 moiety resulted in compounds with femtomolar enzyme activities and cellular antiviral activities in the low nanomolar range culminating in the identification of clinical candidate GW0385. (C) 2006 Elsevier Ltd. All rights reserved.