N,N'-(2,2'-dithiobisbenzoyl)-bis-D-alaninamide

• 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: N,N'-(2,2'-dithiobisbenzoyl)-bis-D-alaninamide
• 英文别名: N,2'-Dithiodibenzoyl)-bis(D-alaninamide)；N-[(2R)-1-amino-1-oxopropan-2-yl]-2-[[2-[[(2R)-1-amino-1-oxopropan-2-yl]carbamoyl]phenyl]disulfanyl]benzamide
• 化学式: C₂₀H₂₂N₄O₄S₂
• 分子量: 446.551
• InChiKey: APQLGDHAFJZRJT-VXGBXAGGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  195
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N,N'-(2,2'-dithiobisbenzoyl)-bis-D-alaninamide 在 三(2-羰基乙基)磷盐酸盐 、 三乙胺 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 (2-Bromo-ethyl)-thiocarbamic acid, S-[2-((R)-1-carbamoyl-ethylcarbamoyl)-phenyl] ester
  参考文献：
  名称：

  基于苯甲酰胺的硫代氨基甲酸酯：一类新的HIV-1 NCp7抑制剂。

  摘要：

  HIV-1核衣壳蛋白NCp7包含两个高度保守的锌指，由于其在病毒复制中起关键作用并且具有突变耐受性，因此被用作AIDS治疗的新靶标。在本文中，我们报告了一类新的具有良好抗病毒活性和低细胞毒性的NCp7抑制剂。

  DOI：

  10.1016/s0960-894x(02)00007-0
• 作为产物：
  描述：

  2, 2'-二硫代二苯甲酸 在 三乙胺 、 N,N'-二异丙基碳二亚胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 生成 N,N'-(2,2'-dithiobisbenzoyl)-bis-D-alaninamide
  参考文献：
  名称：

  基于苯甲酰胺的硫代氨基甲酸酯：一类新的HIV-1 NCp7抑制剂。

  摘要：

  HIV-1核衣壳蛋白NCp7包含两个高度保守的锌指，由于其在病毒复制中起关键作用并且具有突变耐受性，因此被用作AIDS治疗的新靶标。在本文中，我们报告了一类新的具有良好抗病毒活性和低细胞毒性的NCp7抑制剂。

  DOI：

  10.1016/s0960-894x(02)00007-0

文献信息

• Optimization of unique, uncharged thioesters as inhibitors of HIV replication
  作者：Pratibha Srivastava、Marco Schito、Rasem J. Fattah、Toshiaki Hara、Tracy Hartman、Robert W. Buckheit、Jim A. Turpin、John K. Inman、Ettore Appella

  DOI：10.1016/j.bmc.2004.09.032

  日期：2004.12

  A combinatorial chemistry approach was employed to prepare a restricted library of N-substituted S-acyl-2-mercapto-benzamide thioesters. It was shown that many members of this chemotype display anti-HIV activity via their ability to interact with HIV-1, HIV-2, SIV-infected cells, cell-free virus, and chronically and latently infected cells in a manner consistent with targeting of the highly conserved HIV-1 NCp7 zinc fingers. Compounds were initially screened using two different in vitro antiviral assays and evaluated for stability in neutral buffer containing 10% pooled human Serum using a spectrophotometric assay. These data revealed that there was no significant correlation between thioester stability and antiviral activity, however, a slight inverse correlation between serum stability and virucidal activity was noted. Based on the virucidal capability and the ability to select lead compounds to inhibit virus expression from latently infected TNFalpha-induced U1 cells, we next determined if these compounds could prevent HIV cell-to-cell transmission. Several thioesters demonstrated potent inhibition of HIV cell-to-cell transmission with EC50 values in the 80-100 nM range. Thus, we have optimized a series of restricted thioesters and provided evidence that serum stability is not required for antiviral activity. Moreover, selected compounds show potential for development as topical microbicides. (C) 2004 Elsevier Ltd. All rights reserved.
• Benzamide-Based Thiolcarbamates: A New Class of HIV-1 NCp7 Inhibitors
  作者：Atul Goel、Sharlyn J. Mazur、Rasem J. Fattah、Tracy L. Hartman、Jim A. Turpin、Mingjun Huang、William G. Rice、Ettore Appella、John K. Inman

  DOI：10.1016/s0960-894x(02)00007-0

  日期：2002.3

  The HIV-1 nucleocapsid protein NCp7, which contains two highly conserved zinc fingers, is being used as a novel target for AIDS therapy due to its pivotal role in viral replication and its mutationally intolerant nature. Herein we report a new class of NCp7 inhibitors that possess good antiviral activity with low cellular toxicity.

  HIV-1核衣壳蛋白NCp7包含两个高度保守的锌指，由于其在病毒复制中起关键作用并且具有突变耐受性，因此被用作AIDS治疗的新靶标。在本文中，我们报告了一类新的具有良好抗病毒活性和低细胞毒性的NCp7抑制剂。