1,3-dioxo-2-(1-tert-butoxycarbonyl-2,6-dioxopiperidin-3-yl)isoindoline | 220460-69-5

• 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: 1,3-dioxo-2-(1-tert-butoxycarbonyl-2,6-dioxopiperidin-3-yl)isoindoline
• 英文别名: tert-butyl 3-(1,3-dioxoisoindol-2-yl)-2,6-dioxopiperidine-1-carboxylate
• CAS: 220460-69-5
• 化学式: C₁₈H₁₈N₂O₆
• 分子量: 358.351
• InChiKey: ONFFAGNPZWRAMT-UHFFFAOYSA-N

物化性质

• 沸点：
  495.2±55.0 °C(Predicted)
• 密度：
  1.411±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  101
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1,3-dioxo-2-(1-tert-butoxycarbonyl-2,6-dioxopiperidin-3-yl)isoindoline 在 lithium hexamethyldisilazane 、 N-氟代双苯磺酰胺 作用下， 以 四氢呋喃 为溶剂， 以20%的产率得到1,3-dioxo-2-(1-tert-butoxycarbonyl-2,6-dioxo-3-fluoropiperidin-3-yl)isoindoline
  参考文献：
  名称：

  α-Fluoro-substituted thalidomide analogues

  摘要：

  Thalidomide, (1), has made a remarkable comeback from its days of a sedative with teratogenic properties due to its ability to selectively inhibit TNF-alpha, a key pro-inflammatory cytokine and its clinical benefit in the treatment of cancer. Thalidomide contains one chiral center and is known to be chirally unstable under in vitro and in vivo conditions. It has been hypothesized that different biological properties are associated with each isomer. Thus, chirally stable analogues of thalidomide, alpha-fluorothalidomide, (3) and alpha-fluoro-4-aminothalidomide (4) were prepared by electrophilic fluorination. Analogue 3 was found to be cytotoxic and did not inhibit TNF-alpha production in LPS stimulated hPBMC below toxic concentrations. On the other hand, 4 was non-cytotoxic at the tested concentrations and was found to be 830-fold more potent than thalidomide as TNF-alpha inhibitor. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00778-9
• 作为产物：
  描述：

  二碳酸二叔丁酯 、 沙利度胺 在 2-二甲氨基吡啶 作用下， 以 1,4-二氧六环 为溶剂， 生成 1,3-dioxo-2-(1-tert-butoxycarbonyl-2,6-dioxopiperidin-3-yl)isoindoline
  参考文献：
  名称：

  Substituted 2-(2,6-dioxo-3-fluoropiperidin-3-yl)-isoindolines and method

  摘要：

  1-Oxo-2-(2,6-二氧代-3-氟哌啶-3-基)异吲哚啉和1,3-二氧代-2-(2,6-二氧代-3-氟哌啶-3-基)异吲哚啉能够减少哺乳动物体内的炎症细胞因子水平，例如肿瘤坏死因子α（TNFα）。一个典型的实例是1,3-二氧代-2-(2,6-二氧代-3-氟哌啶-3-基)异吲哚啉。

  公开号：

  US05955476A1

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。
• Substituted 2-(2,6 dioxo-3-fluoropiperidin-3-yl)-isoindolines and method
  申请人：Celgene Corporation

  公开号：US05874448A1

  公开（公告）日：1999-02-23

  1-Oxo-2-(2,6-dioxo-3-fluoropiperidin-3-yl)isoindolines and 1,3-dioxo-2-(2,6-dioxo-3-fluoropiperidin-3-yl)isoindolines reduce the levels of TNF.alpha. in a mammal. A typical embodiment is 1,3-dioxo-2-(2,6-dioxo-3-fluoropiperidin-3-yl)-isoindoline.

  1-Oxo-2-(2,6-dioxo-3-fluoropiperidin-3-yl)异吲哚啉和1,3-二氧-2-(2,6-dioxo-3-fluoropiperidin-3-yl)异吲哚啉能降低哺乳动物体内的肿瘤坏死因子α水平。一个典型的实例是1,3-二氧-2-(2,6-dioxo-3-fluoropiperidin-3-yl)异吲哚啉。
• IMIDE-BASED MODULATORS OF PROTEOLYSIS AND ASSOCIATED METHODS OF USE
  申请人：Arvinas, Inc.

  公开号：US20150291562A1

  公开（公告）日：2015-10-15

  The description relates to imide-based 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 invention. 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.

  该描述涉及基于亚醰基的化合物，包括包含它们的双官能团化合物，这些化合物在靶向泛素化调节中发挥作用，特别是根据本发明的双官能团化合物抑制各种多肽和其他蛋白质的降解和/或抑制。具体来说，该描述提供了一种化合物，其中一端含有与小脑素E3泛素连接酶结合的配体，另一端含有结合目标蛋白的基团，使目标蛋白靠近泛素连接酶，以实现该蛋白的降解（和抑制）。可以合成表现出与几乎任何类型的靶向多肽的降解/抑制一致的广泛药理活性的化合物。
• Substituted 2-(2,6-Dioxo-3-Fluoropiperidine-3-YL)-Isoindolines and their use to reduce TNF-alpha Levels
  申请人：CELGENE CORPORATION

  公开号：EP1308444A1

  公开（公告）日：2003-05-07

  1-Oxo-2-(2,6-dioxo-3-fluoropiperidin-3-yl)-isoindolines and 1,3-dioxo-2-(2,6-dioxo-3-fluoropiperidin-3-yl)-isoindolines reduce the levels of inflammatory cytokines such as TNFα in a mammal. A typical embodiment is 1,3-dioxo-2-(2,6-dioxo-3-fluoropiperidin-3-yl)-isoindoline.

  1-氧代-2-(2,6-二氧代-3-氟哌啶-3-基)-异吲哚啉和 1,3-二氧代-2-(2,6-二氧代-3-氟哌啶-3-基)-异吲哚啉可降低哺乳动物体内炎性细胞因子如 TNFα 的水平。一个典型的实施方案是 1,3-二氧代-2-(2,6-二氧代-3-氟哌啶-3-基)-异吲哚啉。
• Substituted 2-(2,6-Dioxo-3-Fluoropiperidine-3-YL)-Isoindolines and their use to reduce TNF-alpha levels
  申请人：CELGENE CORPORATION

  公开号：EP1710242A1

  公开（公告）日：2006-10-11

  1-Oxo-2-(2,6-dioxo-3-fluoropiperidin-3-yl)-isoindolines and 1,3-dioxo-2-(2,6-dioxo-3-fluoropiperidin-3-yl)-isoindolines reduce the levels of inflammatory cytokines such as TNF alpha in a mammal. A typical embodiment is 1,3-dioxo-2-(2,6-dioxo-3-fluoropiperidin-3-yl)-isoindoline.

  1-氧代-2-(2,6-二氧代-3-氟哌啶-3-基)-异吲哚啉和 1,3-二氧代-2-(2,6-二氧代-3-氟哌啶-3-基)-异吲哚啉可降低哺乳动物体内炎性细胞因子如 TNF alpha 的水平。典型的实施方案是 1,3-二氧代-2-(2,6-二氧代-3-氟哌啶-3-基)-异吲哚啉。