(S)-N-indolylmethyloxirane | 950171-30-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (S)-N-indolylmethyloxirane
• 英文别名: (S)-1-(oxiran-2-ylmethyl)-1H-indole
• CAS: 950171-30-9
• 化学式: C₁₁H₁₁NO
• 分子量: 173.214
• InChiKey: LDCGJHXNODDHOO-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.04
• 重原子数：
  13.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  17.46
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  (S)-N-indolylmethyloxirane 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 copper(l) iodide 、 magnesium sulfate 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 17.17h， 生成 (R)-6-((1H-indol-1-yl)methyl)-5,6-dihydro-2H-pyran-2-one
  参考文献：
  名称：

  A low toxic CRM1 degrader: Synthesis and anti-proliferation on MGC803 and HGC27

  摘要：

  Chromosome region maintenance 1 (CRM1) is the sole nuclear exporter of several tumor suppressor, a growth regulatory protein as an attractive cancer drug target. In the present work, a novel CRM1 degrader was discovered from newly synthesized alpha, beta-unsaturated-delta-lactone based on a natural product Goniothalamin. It induces apoptosis of both MGC803 and HGC27 cell lines via degrading CRM1. Selective inhibition was observed for the proliferation of gastric cancer cell lines MGC803, HGC27 comparing to Human Gastric Mucosal Epithelial Cell Line (GES1). For the first time, CRM1 inhibitor or degrader inducing apoptosis in gastric carcinoma was investigated. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112708
• 作为产物：
  描述：

  吲哚 、 右旋环氧氯丙烷 在 sodium hydride 作用下， 以 乙腈 为溶剂， 反应 0.5h， 生成 (S)-N-indolylmethyloxirane
  参考文献：
  名称：

  A low toxic CRM1 degrader: Synthesis and anti-proliferation on MGC803 and HGC27

  摘要：

  Chromosome region maintenance 1 (CRM1) is the sole nuclear exporter of several tumor suppressor, a growth regulatory protein as an attractive cancer drug target. In the present work, a novel CRM1 degrader was discovered from newly synthesized alpha, beta-unsaturated-delta-lactone based on a natural product Goniothalamin. It induces apoptosis of both MGC803 and HGC27 cell lines via degrading CRM1. Selective inhibition was observed for the proliferation of gastric cancer cell lines MGC803, HGC27 comparing to Human Gastric Mucosal Epithelial Cell Line (GES1). For the first time, CRM1 inhibitor or degrader inducing apoptosis in gastric carcinoma was investigated. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112708

文献信息

• Enantioselective Incorporation of Carbon Dioxide into Epoxides Catalyzed by Optically Active Cobalt(II) Complexes
  作者：Wataru Yamada、Yasunori Kitaichi、Hirotaka Tanaka、Tomohide Kojima、Mitsuo Sato、Taketo Ikeno、Tohru Yamada

  DOI：10.1246/bcsj.80.1391

  日期：——

  into an epoxide was developed using an optically active ketoiminatocobalt(II) complex as a chiral Lewis acid. In the presence of a catalytic amount of the cobalt complex and amine base, enantioselective CO 2 fixation with an epoxide proceeded with kinetic resolution to afford the corresponding carbonate along with unreacted epoxide, both of which were optically active. To improve their enantioselectivities

  使用光学活性的酮亚氨基钴 (II) 配合物作为手性路易斯酸开发了 CO 2 对映选择性化学固定到环氧化物中。在催化量的钴络合物和胺碱的存在下，与环氧化物的对映选择性 CO 2 固定进行动力学拆分，得到相应的碳酸盐和未反应的环氧化物，两者都是光学活性的。为了提高它们的对映选择性，研究了钴配合物和胺碱的配体结构。因此，优化的催化体系成功地应用于各种环氧化物，以获得相应的光学活性环状碳酸酯，并以良好的对映选择性回收环氧化物。
• Discovery of tetrahydroisoquinolineindole derivatives as first dual PRMT5 inhibitors/hnRNP E1 upregulators: Design, synthesis and biological evaluation
  作者：Wen-Hui Chu、Na Yang、Jin-He Zhang、Yue Li、Jia-Li Song、Zhi-Peng Deng、Ning Meng、Juan Zhang、Kong-Kai Zhu、Cheng-Shi Jiang

  DOI：10.1016/j.ejmech.2023.115625

  日期：2023.10

  antiproliferative effects against A549 cells by inducing apoptosis and inhibiting cell migration. Importantly, silencing of hnRNP E1 eliminated the antitumor effect of 3m and 3s4 on the apoptosis and migration in A549 cells, suggesting a regulatory relationship between PRMT5 and hnRNP E1. Additionally, compound 3m exhibited high metabolic stability on human liver microsomes (T1/2 = 132.4 min). In SD rats, the

  蛋白精氨酸甲基转移酶5 (PRMT5) 是一种表观遗传学相关酶，已被验证为治疗各种类型癌症的重要治疗靶点。肿瘤抑制因子hnRNP E1的上调也被认为是一种有效的抗肿瘤疗法。本研究设计并制备了一系列四氢异喹啉吲哚杂化物，发现化合物3m和3s4是PRMT5的选择性抑制剂和hnRNP E1的上调剂。分子对接研究表明化合物3m占据PRMT5的底物位点并与氨基酸残基形成必要的相互作用。此外，化合物3m和3s4通过诱导细胞凋亡和抑制细胞迁移对A549细胞发挥抗增殖作用。重要的是，沉默hnRNP E1消除了3m和3s4对A549细胞凋亡和迁移的抗肿瘤作用此外，化合物3m在人肝微粒体上表现出高代谢稳定性（ T 1/2 = 132.4 分钟）。在SD大鼠中， 3m的生物利用度为31.4%，与阳性对照相比，AUC和Cmax这些结果表明，化合物3m是第一类双重 PRMT5 抑制剂和 hnRNP E1 上调剂，值得进一步研究作为潜在的抗癌药物。