2-(6-oxo-2-oxa-5-azaspiro[3.5]nonan-9-yl)isoindoline-1,3-dione | 1449603-80-8

• 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-(6-oxo-2-oxa-5-azaspiro[3.5]nonan-9-yl)isoindoline-1,3-dione
• 英文别名: oxetano-thalidomide；2-(6-Oxo-2-oxa-5-azaspiro[3.5]nonan-9-yl)isoindoline-1,3-dione；2-(6-oxo-2-oxa-5-azaspiro[3.5]nonan-9-yl)isoindole-1,3-dione
• CAS: 1449603-80-8
• 化学式: C₁₅H₁₄N₂O₄
• 分子量: 286.287
• InChiKey: OZCIXBUKIVTJKJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 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：

  (E)-9-(hydroxyimino)-5-(4-methoxybenzyl)-2-oxa-5-azaspiro[3.5]nonan-6-one 在 ammonium cerium (IV) nitrate 、 水 、 氢气 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 乙腈 为溶剂， 反应 15.5h， 生成 2-(6-oxo-2-oxa-5-azaspiro[3.5]nonan-9-yl)isoindoline-1,3-dione
  参考文献：
  名称：

  Synthesis and Stability of Oxetane Analogs of Thalidomide and Lenalidomide

  摘要：

  Oxetanes are used in drug discovery to enable physicochemical and metabolic property enhancement for the structures to which they are grafted. An imide C=O to oxetane swap on thalidomide and lenalidomide templates provides analogs with similar physicochemical and in vitro properties of the parent drugs, with an important exception: oxetane analog 2 displays a clear differentiation with respect to human plasma stability. The prospect of limiting in vivo stability/metabolism, blocking in vivo racemization, and potentially altering teratogenicity is appealing.

  DOI：

  10.1021/ol401705a

文献信息

• CEREBLON LIGANDS AND BIFUNCTIONAL COMPOUNDS COMPRISING THE SAME
  申请人：Arvinas, Inc.

  公开号：US20180215731A1

  公开（公告）日：2018-08-02

  The description relates to cereblon E3 ligase binding compounds, including bifunctional compounds comprising the same, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present disclosure. In particular, the description provides compounds, which contain on one end a ligand which binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. Compounds can be synthesized that exhibit a broad range of pharmacological activities consistent with the degradation/inhibition of targeted polypeptides of nearly any type.

  该描述涉及cereblon E3连接酶结合化合物，包括包含相同成分的双功能化合物，这些化合物作为靶向泛素化的调节剂具有实用价值，尤其是抑制剂，可降解和/或以其他方式抑制根据本公开的双功能化合物。特别是，该描述提供了化合物，其一端含有与cereblon E3泛素连接酶结合的配体，另一端含有与目标蛋白结合的部分，使目标蛋白位于泛素连接酶附近以降解（和抑制）该蛋白。可以合成表现出广泛药理活性的化合物，与几乎所有类型的靶向多肽的降解/抑制一致。
• CRBN LIGANDS AND USES THEREOF
  申请人：Kymera Therapeutics, Inc.

  公开号：US20200347045A1

  公开（公告）日：2020-11-05

  The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of CRBN, and the treatment of CRBN-mediated disorders.
• Synthesis and Stability of Oxetane Analogs of Thalidomide and Lenalidomide
  作者：Johannes A. Burkhard、Georg Wuitschik、Jean-Marc Plancher、Mark Rogers-Evans、Erick M. Carreira

  DOI：10.1021/ol401705a

  日期：2013.9.6

  Oxetanes are used in drug discovery to enable physicochemical and metabolic property enhancement for the structures to which they are grafted. An imide C=O to oxetane swap on thalidomide and lenalidomide templates provides analogs with similar physicochemical and in vitro properties of the parent drugs, with an important exception: oxetane analog 2 displays a clear differentiation with respect to human plasma stability. The prospect of limiting in vivo stability/metabolism, blocking in vivo racemization, and potentially altering teratogenicity is appealing.