2-[2-[2-[4-(tert-butoxycarbonylamino)phenoxy]ethoxy]ethoxy]ethyl-4-methylbenzenesulfonate | 1402230-94-7

• 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: 2-[2-[2-[4-(tert-butoxycarbonylamino)phenoxy]ethoxy]ethoxy]ethyl-4-methylbenzenesulfonate
• 英文别名: 2-[2-[2-[4-[(2-Methylpropan-2-yl)oxycarbonylamino]phenoxy]ethoxy]ethoxy]ethyl 4-methylbenzenesulfonate；2-[2-[2-[4-[(2-methylpropan-2-yl)oxycarbonylamino]phenoxy]ethoxy]ethoxy]ethyl 4-methylbenzenesulfonate
• CAS: 1402230-94-7
• 化学式: C₂₄H₃₃NO₈S
• 分子量: 495.594
• InChiKey: PUDSPGPYFXFXLW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  34
• 可旋转键数：
  15
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  118
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-[2-[2-[4-(tert-butoxycarbonylamino)phenoxy]ethoxy]ethoxy]ethyl-4-methylbenzenesulfonate 在 sodium azide 作用下， 以 乙醇 、 水 为溶剂， 反应 1.0h， 生成 4-[2-[2-(2-叠氮乙氧基)乙氧基]乙氧基]苯胺
  参考文献：
  名称：

  Chemical synthesis and biological validation of immobilized protein kinase inhibitory Leucettines

  摘要：

  Leucettines, a family of marine sponge-derived 2-aminoimidazolone alkaloids, are potent inhibitors of DYRKs (dual-specificity, tyrosine phosphoiylation regulated kinases) and CLKs (cdc2-like kinases). They constitute promising pharmacological leads for the treatment of several diseases, including Alzheimer's disease and Down syndrome. In order to investigate the scope of potential targets of Leucettine L41, a representative member of the chemical class, we designed an affinity chromatography strategy based on agarose-immobilized leucettines. A synthesis protocol for the attachment of a polyethylene (3 or 4 units) linker to L41 was first established. The linker attachment site on L41 was selected on the basis of the co-crystal structure of L41 with several kinases. L41 was then covalently bound to agarose beads through the primary amine located at the end of the linker. Control, kinase inactive Leucettine was also immobilized, as well as free linker devoid of ligand. Extracts of several mouse tissues revealed a complex pattern of interacting proteins, some of which probably resulting from non-specific, hydrophobic binding, while others representing bona fide Leucettine-interacting proteins. DYRK1A and GSK-3 (glycogen synthase kinase-3) were confirmed as interacting targets by Western blotting in various mouse tissues. The Leucettine affinity chromatography resin constitutes a powerful tool to purify and identify the targets of this new promising therapeutic class of molecules. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.01.035
• 作为产物：
  描述：

  三乙二醇单对甲苯磺酸酯 在 4-二甲氨基吡啶 、 potassium carbonate 、 三乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 生成 2-[2-[2-[4-(tert-butoxycarbonylamino)phenoxy]ethoxy]ethoxy]ethyl-4-methylbenzenesulfonate
  参考文献：
  名称：

  SYNTHESIS OF SMALL MOLECULE HISTONE DEACETYLASE 6 DEGRADERS, COMPOUNDS FORMED THEREBY, AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM

  摘要：

  组蛋白去乙酰化酶（“HDAC”）选择性抑制剂与共价键结到一个连接剂上，该连接剂与一个E3泛素连接酶配体共价键结合，以及其盐；含有它们的药物组合物；使用该组合物抑制哺乳动物，包括人类中的肿瘤细胞生长的方法。

  公开号：

  US20200022966A1

文献信息

• Identification and Characterization of a Novel Indoleamine 2,3-Dioxygenase 1 Protein Degrader for Glioblastoma
  作者：Lakshmi R. Bollu、Prashant V. Bommi、Paige J. Monsen、Lijie Zhai、Kristen L. Lauing、April Bell、Miri Kim、Erik Ladomersky、Xinyu Yang、Leonidas C. Platanias、Daniela E. Matei、Marcelo G. Bonini、Hidayatullah G. Munshi、Rintaro Hashizume、Jennifer D. Wu、Bin Zhang、Charles David James、Peiwen Chen、Masha Kocherginsky、Craig Horbinski、Michael D. Cameron、Arabela A. Grigorescu、Bakhtiar Yamini、Rimas V. Lukas、Gary E. Schiltz、Derek A. Wainwright

  DOI：10.1021/acs.jmedchem.2c00771

  日期：2022.12.8

  targeting chimeras (PROTACs) that degrade the IDO1 protein. IDO1-PROTACs were tested for their effects on IDO1 enzyme and non-enzyme activities. After screening a library of IDO1-PROTAC derivatives, a compound was identified that potently degraded the IDO1 protein through cereblon-mediated proteasomal degradation. The IDO1-PROTAC: (i) inhibited IDO1 enzyme activity and IDO1-mediated NF-κB phosphorylation

  吲哚胺 2,3-双加氧酶 1 (IDO1) 是一种有效的免疫抑制酶，可通过色氨酸代谢和非酶功能抑制抗肿瘤免疫反应。迄今为止，大多数 IDO1 靶向方法都集中于抑制色氨酸代谢。然而，此类药物未能改善癌症患者的总体生存率。在这里，我们开发并表征了可降解 IDO1 蛋白的蛋白水解靶向嵌合体 (PROTAC)。测试了 IDO1-PROTAC 对 IDO1 酶和非酶活性的影响。在筛选 IDO1-PROTAC 衍生物文库后，鉴定出一种化合物可以通过 cereblon 介导的蛋白酶体降解有效降解 IDO1 蛋白。 IDO1-PROTAC：(i) 在培养的人胶质母细胞瘤 (GBM) 细胞中抑制 IDO1 酶活性和 IDO1 介导的 NF-κB 磷酸化，(ii) 在体内降解颅内脑肿瘤内的 IDO1 蛋白，以及 (iii) 介导存活对患有明确脑肿瘤的小鼠有益。这项研究鉴定并鉴定了一种新的 IDO1 蛋白降解剂