2-((diphenyl(p-tolyl)methyl)thio)ethan-1-amine | 1364663-36-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 2-((diphenyl(p-tolyl)methyl)thio)ethan-1-amine
• 英文别名: 2-[1-(4-methylphenyl)-1,1-diphenylmethylthio]ethanamine；2-(Diphenyl(P-Tolyl)Methylthio)Ethanamine；2-[(4-methylphenyl)-diphenylmethyl]sulfanylethanamine
• CAS: 1364663-36-4
• 化学式: C₂₂H₂₃NS
• 分子量: 333.497
• InChiKey: OWQZSPCKUCPBPY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  51.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-(dimethylamino)picolinaldehyde 、 2-((diphenyl(p-tolyl)methyl)thio)ethan-1-amine 在 三乙酰氧基硼氢化钠 作用下， 以 1,2-二氯乙烷 为溶剂， 以52 %的产率得到2-(((2-((diphenyl(p-tolyl)methyl)thio)ethyl)amino)methyl)-N,N-dimethylpyridin-4-amine
  参考文献：
  名称：

  基于配体的新型三苯甲基组胺和三苯甲基半胱胺衍生物的设计和合成作为癌症治疗的 SIRT2 抑制剂

  摘要：

  对新型癌症治疗药物的不懈追求导致了多个分子靶点的鉴定，其中 Sirtuin 2 (SIRT2) 引起了极大的关注。本研究对我们报道的基于三苯甲基支架的 SIRT2 抑制剂进行了广泛的 SAR 研究。这项研究涵盖了一系列不同的药物化学方法，以提高先导化合物的活性。在进行SIRT2抑制实验、NCI60细胞毒性测试和细胞周期分析之前，使用NMR和高分辨率质谱确认了合理设计和合成的结构。事实上，我们的策略提供了迄今为止未报道的高活性 SIRT2 抑制剂，特别是 、 、 和 。值得注意的是，自由旋转或锁定三苯甲基部分的苯基上亲脂性对位取代的存在增强了 SIRT2 抑制活性。与此同时，NCI60 检测显示，合成的化合物对不同的癌细胞系表现出显着的活性。有趣的是，该化合物作为一种针对白血病和结肠癌的有效且高度选择性的抗增殖剂而脱颖而出。此外，处理导致 MCF-7 细胞的细胞周期停滞在 G2 期，并且不会引起体外

  DOI：

  10.1016/j.ejmech.2024.116302
• 作为产物：
  描述：

  4-甲基三苯基甲醇 、 半胱胺盐酸盐 在 三氟乙酸 、 碳酸氢钠 作用下， 以 水 、 乙酸乙酯 为溶剂， 以29%的产率得到2-((diphenyl(p-tolyl)methyl)thio)ethan-1-amine
  参考文献：
  名称：

  Inhibition of hepatitis C virus NS5B polymerase by S-trityl-l-cysteine derivatives

  摘要：

  Structure-based studies led to the identification of a constrained derivative of S-trityl-c-cysteine (STLC) scaffold as a candidate inhibitor of hepatitis C virus (HCV) NS5B polymerase. A panel of STLC derivatives were synthesized and investigated for their activity against HCV NS5B. Three STLC derivatives, 9, F-3070, and F-3065, were identified as modest HCV NS5B inhibitors with IC50 values between 22.3 and 39.7 mu M. F-3070 and F-3065 displayed potent inhibition of intracellular NS5B activity in the BHK-NS5B-FRLuc reporter and also inhibited HCV RNA replication in the Huh7/Rep-Feo1b reporter system. Binding mode investigations suggested that the STLC scaffold can be used to develop new NS5B inhibitors by further chemical modification at one of the trityl phenyl group. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.01.010

文献信息

• Optimized <i>S</i>-Trityl-<scp>l</scp>-cysteine-Based Inhibitors of Kinesin Spindle Protein with Potent in Vivo Antitumor Activity in Lung Cancer Xenograft Models
  作者：James A. D. Good、Fang Wang、Oliver Rath、Hung Yi Kristal Kaan、Sandeep K. Talapatra、Dawid Podgórski、Simon P. MacKay、Frank Kozielski

  DOI：10.1021/jm3014597

  日期：2013.3.14

  The mitotic kinesin Eg5 is critical for the assembly of the mitotic spindle and is a promising chemotherapy target. Previously, we identified S-trityl-L-cysteine as a selective inhibitor of Eg5 and developed triphenylbutanamine analogues with improved potency, favorable drug-like properties, but moderate in vivo activity. We report here their further optimization to produce extremely potent inhibitors of Eg5 (K-i(app) < 10 nM) with broad-spectrum activity against cancer cell lines comparable to the Phase II drug candidates ispinesib and SB-743921. They have good oral bioavailability and pharmacolcinetics and induced complete tumor regression in nude mice explanted with lung cancer patient xenografts. Furthermore, they display fewer liabilities with CYP-metabolizing enzymes and hERG compared with ispinesib and SB-743921, which is important given the likely application of Eg5 inhibitors in combination therapies. We present the case for this preclinical series to be investigated in single and combination chemotherapies, especially targeting hematological malignancies.
• THIOETHER-, ETHER-, AND ALKYLAMINE-LINKED HYDROGEN BOND SURROGATE PEPTIDOMIMETICS
  申请人：Arora Paramjit S.

  公开号：US20130123196A1

  公开（公告）日：2013-05-16

  Provided herein are peptidomimetics and their salts having a stable, internally constrained protein secondary structure containing a thioether-, ether-, or alkylamine-linked hydrogen bond surrogate; compositions containing at least one of these, and methods of making and using these.
• COMPOUND FOR USE IN PEPTIDE SYNTHESIS
  申请人：Liu Chuan Fa

  公开号：US20130131286A1

  公开（公告）日：2013-05-23

  The present invention generally relates to processes and methods of peptide and protein synthesis. The present invention also relates to specific compounds for use in such processes and methods. It is shown herein that peptides with a C-terminal tertiary N,N-bis(2-mercaptoethyl)-amide (BMEA) undergo N-to-S acyl transfer at weakly acidic pH to form a transient thioester which can be captured for direct ligation with a cysteinyl peptide. These C-terminal BMEA peptides are easily prepared with standard Fmoc solid-phase synthesis protocols, thus giving a very convenient access to the thioester components for native chemical ligation.
• US9023957B2
  申请人：——

  公开号：US9023957B2

  公开（公告）日：2015-05-05
• Inhibition of hepatitis C virus NS5B polymerase by S-trityl-l-cysteine derivatives
  作者：Daniel B. Nichols、Guy Fournet、K.R. Gurukumar、Amartya Basu、Jin-Ching Lee、Naoya Sakamoto、Frank Kozielski、Ira Musmuca、Benoît Joseph、Rino Ragno、Neerja Kaushik-Basu

  DOI：10.1016/j.ejmech.2012.01.010

  日期：2012.3

  Structure-based studies led to the identification of a constrained derivative of S-trityl-c-cysteine (STLC) scaffold as a candidate inhibitor of hepatitis C virus (HCV) NS5B polymerase. A panel of STLC derivatives were synthesized and investigated for their activity against HCV NS5B. Three STLC derivatives, 9, F-3070, and F-3065, were identified as modest HCV NS5B inhibitors with IC50 values between 22.3 and 39.7 mu M. F-3070 and F-3065 displayed potent inhibition of intracellular NS5B activity in the BHK-NS5B-FRLuc reporter and also inhibited HCV RNA replication in the Huh7/Rep-Feo1b reporter system. Binding mode investigations suggested that the STLC scaffold can be used to develop new NS5B inhibitors by further chemical modification at one of the trityl phenyl group. (C) 2012 Elsevier Masson SAS. All rights reserved.