1,3-dioxo-2-(1-tert-butoxycarbonyl-2,6-dioxo-3-fluoropiperidin-3-yl)isoindoline | 243469-07-0

• 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-dioxo-3-fluoropiperidin-3-yl)isoindoline
• 英文别名: tert-butyl 3-(1,3-dioxoisoindol-2-yl)-3-fluoro-2,6-dioxopiperidine-1-carboxylate
• CAS: 243469-07-0
• 化学式: C₁₈H₁₇FN₂O₆
• 分子量: 376.341
• InChiKey: AYJKOHGAMQWZDT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  27
• 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：
  7

反应信息

• 作为反应物：
  描述：

  1,3-dioxo-2-(1-tert-butoxycarbonyl-2,6-dioxo-3-fluoropiperidin-3-yl)isoindoline 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以93%的产率得到3'-fluorothalidomide
  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 在 4-二甲氨基吡啶 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 生成 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

文献信息

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

  公开号：US05955476A1

  公开（公告）日：1999-09-21

  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-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。
• 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。
• SUBSTITUTED 2-(2,6-DIOXO-3-FLUOROPIPERIDIN-3-YL)-ISOINDOLINES AND THEIR USE TO REDUCE TNFA LEVELS
  申请人：CELGENE CORPORATION

  公开号：EP1062214B1

  公开（公告）日：2003-03-05
• US5955476A
  申请人：——

  公开号：US5955476A

  公开（公告）日：1999-09-21