3-({3-[3-(tert-butylaminomethyl)octahydroisoquinolin-2-yl]-2-hydroxy-1-phenylsulfanylmethylpropylamino}methyl)-2-methylphenol

• 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: 3-({3-[3-(tert-butylaminomethyl)octahydroisoquinolin-2-yl]-2-hydroxy-1-phenylsulfanylmethylpropylamino}methyl)-2-methylphenol
• 英文别名: 3-[[[(2R,3R)-4-[(3S,4aS,8aS)-3-[(tert-butylamino)methyl]-3,4,4a,5,6,7,8,8a-octahydro-1H-isoquinolin-2-yl]-3-hydroxy-1-phenylsulfanylbutan-2-yl]amino]methyl]-2-methylphenol
• 化学式: C₃₂H₄₉N₃O₂S
• 分子量: 539.826
• InChiKey: GFLVUUXVKYVDTA-HOVBUCEYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  38
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  93.1
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  奈非那韦 在 硼烷四氢呋喃络合物 、 哌啶 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 3-({3-[3-(tert-butylaminomethyl)octahydroisoquinolin-2-yl]-2-hydroxy-1-phenylsulfanylmethylpropylamino}methyl)-2-methylphenol
  参考文献：
  名称：

  Amending HIV Drugs: A Novel Small-Molecule Approach To Target Lupus Anti-DNA Antibodies

  摘要：

  Systemic lupus erythematosus is an autoimmune disease that can affect numerous tissues and is characterized by the production of nuclear antigen-directed autoantibodies (e.g., anti-dsDNA). Using a combination of virtual and ELISA-based screens, we made the intriguing discovery that several HIV-protease inhibitors can function as decoy antigens to specifically inhibit the binding of anti-dsDNA antibodies to target antigens such as dsDNA and pentapeptide DWEYS. Computational modeling revealed that HIV-protease inhibitors comprised structural features present in DWEYS and predicted that analogues containing more flexible backbones would possess preferred binding characteristics. To address this, we reduced the internal amide backbone to improve flexibility, producing new small-molecule decoy antigens, which neutralize anti-dsDNA antibodies in vitro, in situ, and in vivo. Pharmacokinetic and SLE model studies demonstrated that peptidomimetic FISLE-412,(1) a reduced HIV protease inhibitor analogue, was well-tolerated, altered serum reactivity to DWEYS, reduced glomeruli IgG deposition, preserved kidney histology, and delayed SLE onset in NZB/W F1 mice.

  DOI：

  10.1021/acs.jmedchem.6b00694

文献信息

• Amending HIV Drugs: A Novel Small-Molecule Approach To Target Lupus Anti-DNA Antibodies
  作者：Sonya VanPatten、Shan Sun、Mingzhu He、Kai Fan Cheng、Ahmad Altiti、Angelos Papatheodorou、Czeslawa Kowal、Venkatesh Jeganathan、James M. Crawford、Ona Bloom、Bruce T. Volpe、Christian Grant、Nathalie Meurice、Thomas R. Coleman、Betty Diamond、Yousef Al-Abed

  DOI：10.1021/acs.jmedchem.6b00694

  日期：2016.10.13

  Systemic lupus erythematosus is an autoimmune disease that can affect numerous tissues and is characterized by the production of nuclear antigen-directed autoantibodies (e.g., anti-dsDNA). Using a combination of virtual and ELISA-based screens, we made the intriguing discovery that several HIV-protease inhibitors can function as decoy antigens to specifically inhibit the binding of anti-dsDNA antibodies to target antigens such as dsDNA and pentapeptide DWEYS. Computational modeling revealed that HIV-protease inhibitors comprised structural features present in DWEYS and predicted that analogues containing more flexible backbones would possess preferred binding characteristics. To address this, we reduced the internal amide backbone to improve flexibility, producing new small-molecule decoy antigens, which neutralize anti-dsDNA antibodies in vitro, in situ, and in vivo. Pharmacokinetic and SLE model studies demonstrated that peptidomimetic FISLE-412,(1) a reduced HIV protease inhibitor analogue, was well-tolerated, altered serum reactivity to DWEYS, reduced glomeruli IgG deposition, preserved kidney histology, and delayed SLE onset in NZB/W F1 mice.