3-(tritylthio)propan-1-amine | 426828-04-8

• 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: 3-(tritylthio)propan-1-amine
• 英文别名: 3‐[(triphenylmethyl)sulfanyl]propan‐1‐amine；3-[(Triphenylmethyl)sulfanyl]propan-1-amine；3-tritylsulfanylpropan-1-amine
• CAS: 426828-04-8
• 化学式: C₂₂H₂₃NS
• 分子量: 333.497
• InChiKey: MTMAYHULNPMPNW-UHFFFAOYSA-N

物化性质

• 熔点：
  48-50 °C
• 沸点：
  459.9±33.0 °C(Predicted)
• 密度：
  1.111±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  24
• 可旋转键数：
  7
• 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：

  3-(tritylthio)propan-1-amine 在 sodium cyanoborohydride 作用下， 以 甲醇 为溶剂， 生成
  参考文献：
  名称：

  Davis–Beirut Reaction: Route to Thiazolo-, Thiazino-, and Thiazepino-2H-indazoles

  摘要：

  Methods for the construction of thiazolo-, thiazino-, and thiazepino-2H-indazoles from o-nitrobenzaldehydes or o-nitrobenzyl bromides and S-trityl-protected 1 degrees-aminothioalkanes are reported. The process consists of formation of the requisite N-(2-nitrobenzyl) (tritylthio)alkylamine, subsequent deprotection of the trityl moiety with TFA, and immediate treatment with aq. KOH in methanol under Davis-Beirut reaction conditions to deliver the target thiazolo-, thiazino-, or thiazepino-2H-indazole in good overall yield. Subsequent S-oxidation gives the corresponding sulfone.

  DOI：

  10.1021/jo501014e
• 作为产物：
  描述：

  三苯甲硫醇 、 3-溴丙胺氢溴酸盐 在 potassium carbonate 作用下， 以 乙醇 为溶剂， 以88 %的产率得到3-(tritylthio)propan-1-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

文献信息

• [EN] AMANITIN CONJUGATES<br/>[FR] CONJUGUÉS D'AMANITINE
  申请人：HEIDELBERG PHARMA GMBH

  公开号：WO2017149077A1

  公开（公告）日：2017-09-08

  The invention relates to a conjugate comprising (a) an amatoxin comprising (i) an amino acid 4 with a 6'-deoxy position; and (ii) an amino acid 8 with an S-deoxy position; (b) a target-binding moiety; and (c) optionally a linker linking said amatoxin and said target-binding moiety. The invention furthermore relates to a pharmaceutical composition comprising such conjugate.

  这项发明涉及一种共轭物，包括(a) 包括(i) 具有6'-去氧位的氨基酸4；和(ii) 具有S-去氧位的氨基酸8 的阿马毒素；(b) 一个靶向结合基团；以及(c) 可选地连接所述阿马毒素和所述靶向结合基团的连接剂。此外，该发明还涉及包含这种共轭物的药物组合物。
• Molecular Design of Cyclic Peptides with Cell Membrane Permeability and Development of MDMX-p53 Inhibitor
  作者：Mai Mizuno-Kaneko、Ichihiko Hashimoto、Kenta Miyahara、Masahiro Kochi、Noriyuki Ohashi、Kyosuke Tsumura、Koo Suzuki、Takashi Tamura

  DOI：10.1021/acsmedchemlett.3c00102

  日期：2023.9.14

  Cyclic peptides have been expected to be one of the modalities of intracellular protein–protein interaction (PPI) inhibitors, but they are generally known to have low cell membrane permeability. In this study, we focused on the conformation of cyclic peptides in the cell membrane to determine the requirement for their cell membrane permeability through passive diffusion. Utilizing the requirement,

  环肽被认为是细胞内蛋白质-蛋白质相互作用（PPI）抑制剂的一种形式，但众所周知，它们的细胞膜通透性较低。在本研究中，我们重点关注细胞膜中环肽的构象，以确定其通过被动扩散对细胞膜渗透性的要求。利用这一要求，我们通过计算化学寻找对MDMX具有高亲和力的结构，并获得了环肽19 （ P app = 0.80 × 10 –6 cm s –1 ，IC 50 = 0.07 μM）。
• AMANITIN CONJUGATES
  申请人：Heidelberg Pharma GmbH

  公开号：EP3222292A1

  公开（公告）日：2017-09-27

  The invention relates to a conjugate comprising (a) an amatoxin comprising (i) an amino acid 4 with a 6'-deoxy position; and (ii) an amino acid 8 with an S-deoxy position; (b) a target-binding moiety; and (c) optionally a linker linking said amatoxin and said target-binding moiety. The invention furthermore relates to a pharmaceutical composition comprising such conjugate.

  本发明涉及一种共轭物，包括(a)一种包含(i)具有 6'-脱氧位的氨基酸 4 和(ii)具有 S-脱氧位的氨基酸 8 的阿马毒素；(b)一种靶结合分子；以及(c)连接所述阿马毒素和所述靶结合分子的连接剂。本发明还涉及一种包含这种共轭物的药物组合物。
• Structure–Activity Relationship of <i>S</i>-Trityl-<scp>l</scp>-Cysteine Analogues as Inhibitors of the Human Mitotic Kinesin Eg5
  作者：Salvatore DeBonis、Dimitrios A. Skoufias、Rose-Laure Indorato、François Liger、Bernard Marquet、Christian Laggner、Benoît Joseph、Frank Kozielski

  DOI：10.1021/jm070606z

  日期：2008.3.13

  The human kinesin Eg5 is a potential drug target for cancer chemotherapy. Eg5 specific inhibitors cause cells to block in mitosis with a characteristic monoastral spindle phenotype. Prolonged metaphase block eventually leads to apoptotic cell death. S-trityl-L-cysteine (STLC) is a tight-binding inhibitor of Eg5 that prevents mitotic progression. It has proven antitumor activity as shown in the NCI 60 tumor cell line screen. It is of considerable interest to define the minimum chemical structure that is essential for Eg5 inhibition and to develop more potent STLC analogues. An initial structure-activity relationship study on a series of STLC analogues reveals the minimal skeleton necessary for Eg5 inhibition as well as indications of how to obtain more potent analogues. The most effective compounds investigated with substitutions at the paraposition of one phenyl ring have an estimated K-i(app) of 100 nM in vitro and induce mitotic arrest with an EC50 of 200 nM.
• Spiro[(dihydropyrazin-2,5-dione)-6,3′-(2′,3′-dihydrothieno[2,3-<i>b</i>]naphtho-4′,9′-dione)]-Based Cytotoxic Agents: Structure–Activity Relationship Studies on the Substituent at N4-Position of the Diketopiperazine Domain
  作者：Isabel Gomez-Monterrey、Pietro Campiglia、Alfonso Carotenuto、Paola Stiuso、Alessia Bertamino、Marina Sala、Claudio Aquino、Paolo Grieco、Silvana Morello、Aldo Pinto、Pio Ianelli、Ettore Novellino

  DOI：10.1021/jm7013056

  日期：2008.5.1

  Analogues of the previously reported potent cytotoxic spiro[(dihydropyrazine-2,5-dione)-6,3'-(2',3'-dihydrothieno[2,3-b]naphtho-4',9'-dione)] derivatives (3, 3') were prepared to explore new structural requirements at the diketopiperazine domain for the cytotoxic activity. The in vitro activity was evaluated against the MCF-7 human breast carcinoma and SW 620 human colon carcinoma cell lines. The 4-[(2-N,N-dimethyl)amino]ethyl (6i), and the 4-(2-pyrrolydin)ethyl (61) derivatives emerged as the most potent compounds of this series, with a cytotoxic activity comparable to that of doxorubicin. These compounds, in both racemic and pure enantiomeric forms, showed also a high efficacy in cell lines resistant to doxorubicin (MCF-7/Dx) and in cell lines that were highly resistant to treatment with doxorubicin, such as HEK-293 (kidney), M-14 (melanoma), and HeLa (cervical adenocarcinoma) human cell lines. In addition, the effects on growth and cell cycle progression in CaCo-2 cell fine (colon adenocarcinoma) and DNA-binding properties were investigated.