2-(17-hydroxy-3,6,9,12,15-pentaoxaheptadecyl)isoindoline-1,3-dione | 141282-27-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 2-(17-hydroxy-3,6,9,12,15-pentaoxaheptadecyl)isoindoline-1,3-dione
• 英文别名: 2-[2-[2-[2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethyl]isoindole-1,3-dione
• CAS: 141282-27-1
• 化学式: C₂₀H₂₉NO₈
• 分子量: 411.452
• InChiKey: RCTJNFGESFQLBC-UHFFFAOYSA-N

物化性质

• 沸点：
  542.7±50.0 °C(Predicted)
• 密度：
  1.229±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  29
• 可旋转键数：
  17
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  104
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-(17-hydroxy-3,6,9,12,15-pentaoxaheptadecyl)isoindoline-1,3-dione 在 potassium hydrogencarbonate 、 三乙胺 、 sodium iodide 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 34.0h， 生成 tri-tert-butyl 2,2',2''-(10-(17-(1,3-dioxoisoindolin-2-yl)-3,6,9,12,15-pentaoxaheptadecyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetate
  参考文献：
  名称：

  cRGD Peptide-Conjugated Icosahedral closo-B₁₂^2- Core Carrying Multiple Gd³⁺-DOTA Chelates for α_vβ₃ Integrin-Targeted Tumor Imaging (MRI)

  摘要：

  A vertex-differentiated icosahedral closo-B-12(2-) core was utilized to construct a alpha(v)beta(3) integrin receptor-targeted (via cRGD peptide) high payload MRI contrast agent (CA-12) carrying 11 copies of Gd3+-DOTA chelates attached to the closo-B-12(2-) surface via suitable linkers. The resulting polyfunctional MRI contrast agent possessed a higher relaxivity value per-Gd compared to Omniscan, a small molecular contrast agent commonly used in clinical settings. The alpha(v)beta(3) integrin receptor specificity of CA-12 was confirmed via in vitro cellular binding experiments and in vivo MRI of mice bearing human PC-3 prostate cancer xenografts. Integrin alpha(v)beta(3)-positive MDA-MB-231 cells exhibited 300% higher uptake of CA-12 than alpha(v)beta(3)-negative T47D cells. Serial T1-weighted MRI showed superior contrast enhancement of tumors by CA-12 compared to both a nontargeted 12-fold Gd3+-DOTA closomer control (CA-7) and Omniscan. Contrast enhancement by CA-12 persisted for 4 h postinjection, and subsequent enhancement of kidney tissue indicated a renal elimination route similar to Omniscan. No toxic effects of CA-12 were apparent in any mice for up to 24 h postinjection. Post-mortem ICP-OES analysis at 24 h detected no residual Gd in any of the tissue samples analyzed.

  DOI：

  10.1021/ic302340c
• 作为产物：
  描述：

  六甘醇 在 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-(17-hydroxy-3,6,9,12,15-pentaoxaheptadecyl)isoindoline-1,3-dione
  参考文献：
  名称：

  荧光AF64394类似物的开发可实现孤立的 A 类 GPCR GPR3 的实时结合研究

  摘要：

  孤儿 G 蛋白偶联受体 （oGPCR） GPR3 代表了治疗阿尔茨海默病和代谢紊乱的潜在药物靶点。然而，有限的药理学分析工具箱阻碍了高级配体的开发。在这里，我们开发了化合物-GPR3 相互作用的信号转导通路非依赖性读数。从最有效的 GPR3 配体的计算结合姿势预测开始，我们设计了一系列荧光 AF64394 类似物，并评估了它们对基于 BRET 的结合研究的适用性。最有效的配体 45 （UR-MB-355） 与 GPR3 和密切相关的受体 GPR6 和 GPR12 结合，具有相似的亚微摩尔亲和力。此外，我们发现与 45 相比，AF64394 以不同的模式参与 GPR3，并且与 GPR3 激动剂二苯碘氯化铵的共孵育研究揭示了 45 结合的变构调节。这些见解为 GPR3 活性的药理学操作提供了新的线索。这种新颖的结合测定将促进通过这些药理学上具有吸引力的 oGPCR 发挥作用的未来药物的开发。

  DOI：

  10.1021/acs.jmedchem.3c01707

文献信息

• IRAK DEGRADERS AND USES THEREOF
  申请人：Kymera Therapeutics, Inc.

  公开号：US20190192668A1

  公开（公告）日：2019-06-27

  The present invention provides compounds, compositions thereof, and methods of using the same.

  本发明提供了化合物、其组合物以及使用这些化合物的方法。
• Affinity resin
  申请人：Tanaka Akito

  公开号：US20070167594A1

  公开（公告）日：2007-07-19

  A resin which is prepared by polymerizing a monomer component incorporating a hydrophilic spacer, and a ligand-immobilized solid phase carrier obtained by immobilizing a ligand to the resin, are capable of reducing the non-specific adsorption of substances, other than the target molecule for the ligand, which mingle in the sample, to the resin and/or the ligand. Therefore, target molecule search, identification and the like with less noise are enabled.

  一种树脂通过聚合包含亲水间隔的单体组分，以及通过将配体固定在树脂上获得的配体固定化固相载体，能够减少除了配体的目标分子以外的杂质在样品中与树脂和/或配体结合的非特异性吸附。因此，可以实现更少噪音的目标分子搜索、鉴定等。
• AFFINITY RESIN
  申请人：Reverse Proteomics Research Institute Co., Ltd

  公开号：EP1674486A1

  公开（公告）日：2006-06-28

  A resin which is prepared by polymerizing a monomer component incorporating a hydrophilic spacer, and a ligand-immobilized solid phase carrier obtained by immobilizing a ligand to the resin, are capable of reducing the non-specific adsorption of substances, other than the target molecule for the ligand, which mingle in the sample, to the resin and/or the ligand. Therefore, target molecule search, identification and the like with less noise are enabled.

  通过聚合含有亲水间隔物的单体成分而制备的树脂，以及通过将配体固定在树脂上而获得的配体固定固相载体，能够减少混杂在样品中的配体目标分子以外的物质对树脂和/或配体的非特异性吸附。因此，在进行目标分子搜索、识别等工作时，噪音较小。
• IRAK degraders and uses thereof
  申请人：Kymera Therapeutics, Inc.

  公开号：US10874743B2

  公开（公告）日：2020-12-29

  The present invention provides compounds, compositions thereof, and methods of using the same.

  本发明提供了化合物、其组合物以及使用方法。
• Improvement of solid material for affinity resins by application of long PEG spacers to capture the whole target complex of FK506
  作者：Miyuki Mabuchi、Tadashi Shimizu、Masahiro Ueda、Kuniko Mitamura、Shigeo Ikegawa、Akito Tanaka

  DOI：10.1016/j.bmcl.2015.05.014

  日期：2015.7

  Solid materials for affinity resins bearing long PEG spacers between a functional group used for immobilization of a bio-active compound and the solid surface were synthesized to capture not only small target proteins but also large and/or complex target proteins. Solid materials with PEG1000 or PEG2000 as spacers, which bear a benzenesulfonamide derivative, exhibited excellent selectivity between the specific binding protein carbonic anhydrase type II (CAII) and non-specific ones. These materials also exhibited efficacy in capturing a particular target at a maximal amount. Affinity resins using solid materials with PEG1000 or PEG2000 spacers, bear a FK506 derivative, successfully captured the whole target complex of specific binding proteins at the silver staining level, while all previously known affinity resins with solid materials failed to achieve this objective. These novel affinity resins captured other specific binding proteins such as dynamin and neurocalcin delta as well. (C) 2015 Elsevier Ltd. All rights reserved.