6-[[(2,2-Diethoxyethyl)amino]methyl]-5,8-dimethyl-9H-carbazol-3-yl 2,2-dimethylpropanoate | 1027280-78-9

• 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: 6-[[(2,2-Diethoxyethyl)amino]methyl]-5,8-dimethyl-9H-carbazol-3-yl 2,2-dimethylpropanoate
• 英文别名: [6-[(2,2-diethoxyethylamino)methyl]-5,8-dimethyl-9H-carbazol-3-yl] 2,2-dimethylpropanoate
• CAS: 1027280-78-9
• 化学式: C₂₆H₃₆N₂O₄
• 分子量: 440.583
• InChiKey: NABQIHOQKJKHMS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  32
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  72.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-[[(2,2-Diethoxyethyl)amino]methyl]-5,8-dimethyl-9H-carbazol-3-yl 2,2-dimethylpropanoate 在 盐酸 、 4-二甲氨基吡啶 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 41.5h， 生成
  参考文献：
  名称：

  Synthesis and Antitumor Activity of 9-Acyloxyellipticines.

  摘要：

  合成了多种水溶性9-酰氧基椭圆碱衍生物，以寻找具有强抗肿瘤活性的化合物。通过静脉给药评估了对小鼠几种肿瘤（P388白血病、结肠26、刘易斯肺癌和B16黑色素瘤）的抗肿瘤活性。许多化合物表现出良好的抗肿瘤活性；特别是戊二酸衍生物（5o）显示出强的抗肿瘤活性。该化合物（5o）可能通过体内酶催化的水解转化为9-羟基椭圆碱（2）。

  DOI：

  10.1248/cpb.45.1156
• 作为产物：
  描述：

  6 - 甲氧基-1,4 - 二甲基-9H-咔唑 在 platinum(IV) oxide 氢气 、 对甲苯磺酸 、 sodium iodide 、 三氯氧磷 作用下， 以 乙醇 、 甲苯 、 乙腈 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 9.5h， 生成 6-[[(2,2-Diethoxyethyl)amino]methyl]-5,8-dimethyl-9H-carbazol-3-yl 2,2-dimethylpropanoate
  参考文献：
  名称：

  Synthesis and Antitumor Activity of 9-Acyloxyellipticines.

  摘要：

  合成了多种水溶性9-酰氧基椭圆碱衍生物，以寻找具有强抗肿瘤活性的化合物。通过静脉给药评估了对小鼠几种肿瘤（P388白血病、结肠26、刘易斯肺癌和B16黑色素瘤）的抗肿瘤活性。许多化合物表现出良好的抗肿瘤活性；特别是戊二酸衍生物（5o）显示出强的抗肿瘤活性。该化合物（5o）可能通过体内酶催化的水解转化为9-羟基椭圆碱（2）。

  DOI：

  10.1248/cpb.45.1156

文献信息

• [EN] METHOD FOR TREATING ALS/FTD THROUGH DEGRADATION OF RNA REPEAT EXPANSION<br/>[FR] MÉTHODE DE TRAITEMENT D'ALS/FTD PAR DÉGRADATION DE L'EXPANSION DE RÉPÉTITION D'ARN
  申请人：[en]THE SCRIPPS RESEARCH INSTITUTE

  公开号：WO2022086851A1

  公开（公告）日：2022-04-28

  Described are small molecule embodiments, ALS compounds, that bind with the (G4C2)expRNA repeat transcription of the chromosome 9 open reading frame 72 involved in amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD). These ALS compounds comprise a pyridocarbazole moiety having at least one substituent. Preferred ALS compounds comprise bridged dimers of the pyridocarbazole moiety in which the bridge between the two pyridocarbazole moieties is a polyoxyethylenyl group or an aminobispolyoxyethylenyl group.
• The Hairpin Form of r(G4C2)exp in c9ALS/FTD Is Repeat-Associated Non-ATG Translated and a Target for Bioactive Small Molecules
  作者：Zi-Fu Wang、Andrei Ursu、Jessica L. Childs-Disney、Rea Guertler、Wang-Yong Yang、Viachaslau Bernat、Suzanne G. Rzuczek、Rita Fuerst、Yong-Jie Zhang、Tania F. Gendron、Ilyas Yildirim、Brendan G. Dwyer、Joseph E. Rice、Leonard Petrucelli、Matthew D. Disney

  DOI：10.1016/j.chembiol.2018.10.018

  日期：2019.2

  The most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is an expanded G(4)C(2) repeat [(G(4)C(2))(exp)] in C9ORF72. ALS/FTD-associated toxicity has been traced to the RNA transcribed from the repeat expansion [r(G(4)C(2))(exp)], which sequesters RNA-binding proteins (RBPs) and undergoes repeat-associated non-ATG (RAN) translation to generate toxic dipeptide repeats. Using in vitro and cell-based assays, we identified a small molecule (4) that selectively bound r(G(4)C(2))(exp), prevented sequestration of an RBP, and inhibited RAN translation. Indeed, biophysical characterization showed that 4 selectively bound the hairpin form of r(G(4)C(2))(exp), and nuclear magnetic resonance spectroscopy studies and molecular dynamics simulations defined this molecular recognition event. Cellular imaging revealed that 4 localized to r(G(4)C(2))(exp) cytoplasmic foci, the putative sites of RAN translation. Collectively, these studies highlight that the hairpin structure of r(G(4)C(2))(exp) is a therapeutically relevant target and small molecules that bind it can ameliorate c9ALS/FTD-associated toxicity.
• Synthesis and Antitumor Activity of 9-Acyloxyellipticines.
  作者：Naoyuki HARADA、Kunihiko OZAKI、Kouji ODA、Noriyuki NAKANISHI、Motoaki OHASHI、Tomiki HASHIYAMA、Kenji TSUJIHARA

  DOI：10.1248/cpb.45.1156

  日期：——

  Various kinds of water-soluble 9-acyloxyellipticine derivatives were synthesized in a search for compounds with potent antitumor activity. Antitumor activities against several tumors in mice (P388 leukemia, colon 26, Lewis lung carcinoma and B16 melanoma) were evaluated by using intravenous administration. Many compounds exhibited good antitumor activities; in particular, the glutarate derivative (5o) showed potent antitumor activity. This comopound (5o) may be converted to 9-hydroxyellipticine (2) by enzyme-catalyzed hydrolysis in the body.

  合成了多种水溶性9-酰氧基椭圆碱衍生物，以寻找具有强抗肿瘤活性的化合物。通过静脉给药评估了对小鼠几种肿瘤（P388白血病、结肠26、刘易斯肺癌和B16黑色素瘤）的抗肿瘤活性。许多化合物表现出良好的抗肿瘤活性；特别是戊二酸衍生物（5o）显示出强的抗肿瘤活性。该化合物（5o）可能通过体内酶催化的水解转化为9-羟基椭圆碱（2）。