2-(2,6-dioxo-3-piperidinyl)-5-benzyloxy-1H-isoindole-1,3(2H)-dione | 94464-27-4

• 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-(2,6-dioxo-3-piperidinyl)-5-benzyloxy-1H-isoindole-1,3(2H)-dione
• 英文别名: 5-benzyloxy-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione；5-benzyloxy-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione；α-(4-Benzyloxy-phthalimido)-glutarimid；5-(Benzyloxy)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione；2-(2,6-dioxopiperidin-3-yl)-5-phenylmethoxyisoindole-1,3-dione
• CAS: 94464-27-4
• 化学式: C₂₀H₁₆N₂O₅
• 分子量: 364.357
• InChiKey: ZFPHORBDRPKZFE-UHFFFAOYSA-N

物化性质

• 熔点：
  172-176 °C
• 沸点：
  628.0±55.0 °C(Predicted)
• 密度：
  1.420±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  92.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(2,6-dioxo-3-piperidinyl)-5-benzyloxy-1H-isoindole-1,3(2H)-dione 在 palladium on activated charcoal 氢气 、 溶剂黄146 作用下， 以 乙酸乙酯 为溶剂， 反应 1.0h， 以59%的产率得到4-羟基沙利度胺
  参考文献：
  名称：

  Mono- and Dihydroxylated Metabolites of Thalidomide: Synthesis and TNF-.ALPHA. Production-Inhibitory Activity

  摘要：

  少量和双羟基化的沙利度胺代谢物被高效制备和表征，并评估了它们对人单核细胞白血病细胞系 THP-1 中肿瘤坏死因子 (TNF)-α 生产的抑制活性。5,N-二羟基沙利度胺是一种比沙利度胺更强效的 TNF-α 生产抑制剂。

  DOI：

  10.1248/cpb.54.1709
• 作为产物：
  描述：

  4-羟基邻苯二甲酸 在 氢氧化钾 、 TEA 、 1-羟基苯并三唑一水物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 85.0h， 生成 2-(2,6-dioxo-3-piperidinyl)-5-benzyloxy-1H-isoindole-1,3(2H)-dione
  参考文献：
  名称：

  Mono- and Dihydroxylated Metabolites of Thalidomide: Synthesis and TNF-.ALPHA. Production-Inhibitory Activity

  摘要：

  少量和双羟基化的沙利度胺代谢物被高效制备和表征，并评估了它们对人单核细胞白血病细胞系 THP-1 中肿瘤坏死因子 (TNF)-α 生产的抑制活性。5,N-二羟基沙利度胺是一种比沙利度胺更强效的 TNF-α 生产抑制剂。

  DOI：

  10.1248/cpb.54.1709

文献信息

• COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF ANDROGEN RECEPTOR
  申请人：Arvinas, Inc.

  公开号：US20180099940A1

  公开（公告）日：2018-04-12

  The present disclosure relates to bifunctional compounds, which find utility to degrade and (inhibit) Androgen Receptor. In particular, the present disclosure is directed to compounds, which contain on one end a cereblon ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds Androgen Receptor, such that Androgen Receptor is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of Androgen Receptor. The present disclosure exhibits a broad range of pharmacological activities associated with compounds according to the present disclosure, consistent with the degradation/inhibition of Androgen Receptor.

  本公开涉及双功能化合物，其用于降解和（抑制）雄激素受体。具体而言，本公开涉及包含一端结合到E3泛素连接酶的谷氨酰腺苷环配体，另一端结合到雄激素受体的部分的化合物，使得雄激素受体与泛素连接酶靠近，以实现雄激素受体的降解（和抑制）。本公开展示了与根据本公开涉及的化合物相关的广泛的药理活性范围，与雄激素受体的降解/抑制一致。
• Syntheses of Aromatic Substituted 6′-Thiothalidomides
  作者：Nigel Greig、Weiming Luo、Qian-sheng Yu、David Tweedie、Jeffery Deschamps、Damon Parrish、Harold Holloway、Yazhou Li、Arnold Brossi

  DOI：10.1055/s-0028-1083179

  日期：——

  A resurgence of interest in thalidomide has occurred as a consequence of its diverse immunomodulatory and anticancer actions, which has fuelled interest in synthetic analogues with higher potencies or less undesirable side effect profiles. Several novel aromatic substituted 6′-thiothalidomides were synthesized whose synthetic route and strategy were developed on the basis of an analysis of reaction mechanisms. The regioselectivity of mono-thionation of aromatic substituted thalidomides with Lawesson’s reagent is described, and the chemoselectivity of hydrogenation between the nitro­ group and 6′-thiocarbonyl group is discussed. Full characterization of eight substituted 6′-thiothalidomides is reported.

  由于沙利度胺具有多种免疫调节和抗癌作用，人们对沙利度胺的兴趣重新燃起，这激发了人们对具有更高效力或更少不良副作用的合成类似物的兴趣。合成了几种新型芳香族取代的6′-硫代沙利度胺，并在反应机理分析的基础上制定了合成路线和策略。描述了用Lawesson试剂对芳香族取代的沙利度胺进行一硫代反应的区域选择性，并讨论了硝基与6'-硫代羰基之间氢化的化学选择性。报道了八种取代的 6'-硫代沙利度胺的完整表征。
• Thalidomide analogs and methods of use
  申请人：THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES

  公开号：US10730835B2

  公开（公告）日：2020-08-04

  Thalidomide analogs and methods of using the thalidomide analogs are disclosed. Some embodiments of the disclosed compounds exhibit anti-angiogenic and/or anti-inflammatory activity. Certain embodiments of the disclosed compounds are non-teratogenic.

  本研究公开了沙利度胺类似物和使用沙利度胺类似物的方法。所公开化合物的某些实施方案具有抗血管生成和/或抗炎活性。所公开化合物的某些实施方案不致畸。
• Tubulin-polymerization inhibitors derived from thalidomide
  作者：Shunsuke Inatsuki、Tomomi Noguchi、Hiroyuki Miyachi、Sawako Oda、Toyotaka Iguchi、Masahiro Kizaki、Yuichi Hashimoto、Hisayoshi Kobayashi

  DOI：10.1016/j.bmcl.2004.10.072

  日期：2005.1

  2-(2,6-Diisopropylphenyl)-5-hydroxy-1H-isoindole-1,3-dione (5HPP-33), which was obtained during our previous structural development studies on thalidomide, was revealed to possess potent tubulin-polymerization-inhibiting activity, comparable to that of the known tubulin-polymerization inhibitors, rhizoxin and colchicine. A major metabolite of thalidomide, 5-hydroxythalidomide, which possesses a hydroxyl group at the position corresponding to that of 5HPP-33, also showed moderate inhibitory activity. (C) 2004 Elsevier Ltd. All rights reserved.
• THALIDOMIDE ANALOGS AND METHODS OF USE
  申请人：The USA, as represented by the Secretary, Department of Health and Human Services

  公开号：US20200325102A1

  公开（公告）日：2020-10-15

  Thalidomide analogs and methods of using the thalidomide analogs are disclosed. Some embodiments of the disclosed compounds exhibit anti-angiogenic and/or anti-inflammatory activity. Certain embodiments of the disclosed compounds are non-teratogenic.