3-(4-(benzyloxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione | 1061605-65-9

• 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: 3-(4-(benzyloxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione
• 英文别名: 3-(3-oxo-7-phenylmethoxy-1H-isoindol-2-yl)piperidine-2,6-dione
• CAS: 1061605-65-9
• 化学式: C₂₀H₁₈N₂O₄
• 分子量: 350.374
• InChiKey: MOGHNNIVWVOLSV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  75.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-(4-羟基-1-氧代异吲哚-2-基)哌啶-2,6-二酮 、 溴甲苯 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 18.0h， 以8.4%的产率得到3-(4-(benzyloxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione
  参考文献：
  名称：

  Discovery of CRBN E3 Ligase Modulator CC-92480 for the Treatment of Relapsed and Refractory Multiple Myeloma

  摘要：

  Many patients with multiple myeloma (MM) initially respond to treatment with modern combination regimens including immunomodulatory agents (lenalidomide and pomalidomide) and proteasome inhibitors. However, some patients lack an initial response to therapy (i.e., are refractory), and although the mean survival of MM patients has more than doubled in recent years, most patients will eventually relapse. To address this need, we explored the potential of novel cereblon E3 ligase modulators (CELMoDs) for the treatment of patients with relapsed or refractory multiple myeloma (RRMM). We found that optimization beyond potency of degradation, including degradation efficiency and kinetics, could provide efficacy in a lenalidomide-resistant setting. Guided by both phenotypic and protein degradation data, we describe a series of CELMoDs for the treatment of RRMM, culminating in the discovery of CC-92480, a novel protein degrader and the first CELMoD to enter clinical development that was specifically designed for efficient and rapid protein degradation kinetics.

  DOI：

  10.1021/acs.jmedchem.9b01928

文献信息

• 4'-O-SUBSTITUTED ISOINDOLINE DERIVATIVES AND COMPOSITIONS COMPRISING AND METHODS OF USING THE SAME
  申请人：RUCHELMAN Alexander L.

  公开号：US20120165536A1

  公开（公告）日：2012-06-28

  Provided are 4′-O substituted isoindoline compounds, and pharmaceutically acceptable salts, solvates, clathrates, stereoisomers, and prodrugs thereof. Methods of use, and pharmaceutical compositions of these compounds are disclosed.

  提供了4'-O取代的异吲哚啉化合物及其药学上可接受的盐、溶剂合物、包合物、立体异构体和前药。公开了这些化合物的使用方法和制备药物组合物的方法。
• 4′-O-substituted isoindoline derivatives and compositions comprising and methods of using the same
  申请人：Celgene Corporation

  公开号：US10385037B2

  公开（公告）日：2019-08-20

  Provided are 4′-O substituted isoindoline compounds, and pharmaceutically acceptable salts, solvates, clathrates, stereoisomers, and prodrugs thereof. Methods of use, and pharmaceutical compositions of these compounds are disclosed.

  本文提供了 4′-O 取代的异吲哚啉化合物及其药学上可接受的盐、溶解物、凝胶体、立体异构体和原药。还公开了这些化合物的使用方法和药物组合物。
• METHODS FOR TREATING CANCER USING TOR KINASE INHIBITOR COMBINATION THERAPY
  申请人：Signal Pharmaceuticals, LLC

  公开号：US20140314752A1

  公开（公告）日：2014-10-23

  Provided herein are methods for treating or preventing a cancer, comprising administering an effective amount of a TOR kinase inhibitor and an effective amount of an IMiD® immunomodulatory drug to a patient having a cancer.
• CEREBLON ISOFORMS AND THEIR USE AS BIOMARKERS FOR THERAPEUTIC TREATMENT
  申请人：Celgene Corporation

  公开号：US20150152511A1

  公开（公告）日：2015-06-04

  Provided herein are cereblon isoforms and methods of their use as biomarkers for treating a disease, disorder, or condition with a treatment compound, e.g., thalidomide, lenalidomide, pomalidomide, 3-(5-amino-2-methyl-4-oxoquinazolin-3(4H)-yl)-piperidine-2,6-dione, or (S)-3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione.
• US9181216B2
  申请人：——

  公开号：US9181216B2

  公开（公告）日：2015-11-10