3'-fluorothalidomide | 220460-55-9

• 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'-fluorothalidomide
• 英文别名: 1,3-dioxo-2-(2,6-dioxo-3-fluoropiperidine-3-yl) isoindoline；1,3-Dioxo-2-(2,6-dioxo-3-fluoropiperidin-3-yl)isoindoline；2-(3-fluoro-2,6-dioxopiperidin-3-yl)isoindole-1,3-dione
• CAS: 220460-55-9
• 化学式: C₁₃H₉FN₂O₄
• 分子量: 276.224
• InChiKey: SCJORWDJJJWLJD-UHFFFAOYSA-N

物化性质

• 熔点：
  238-240 °C
• 沸点：
  485.3±45.0 °C(Predicted)
• 密度：
  1.57±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  83.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3'-fluorothalidomide 在 4-二甲氨基吡啶 、 potassium carbonate 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 [(3S)-3-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-3-fluoro-2,6-dioxo-piperidin-1-yl]-acetic acid 1,6-dibromonaphthalen-2-yl ester
  参考文献：
  名称：

  (R)- and (S)-3-Fluorothalidomides:  Isosteric Analogues of Thalidomide

  摘要：

  3-Fluorothalidomide, a nonracemizable isosteric analogue of thalidomide, was successfully prepared by perchloryl fluoride fluorination of a 3-phthalimidopiperidin-2-one derivative followed by RuO2 oxidation, In the preliminary biological evaluation of (R)- and (S)-enantiomers, it was shown that the (S)-isomer was found to be more active than both the (R)-isomer and the racemic thalidomide in lipopolysaccharide-induced TNF-a production enhancement produced from human peripheral blood lymphocytes cultivated in vitro.

  DOI：

  10.1021/ol9902172
• 作为产物：
  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

文献信息

• [EN] AMINE-LINKED C3-GLUTARIMIDE DEGRONIMERS FOR TARGET PROTEIN DEGRADATION<br/>[FR] DÉGRONIMÈRES DE C3-GLUTARIMIDE LIÉS À UNE AMINE POUR LA DÉGRADATION DE PROTÉINES CIBLES
  申请人：C4 THERAPEUTICS INC

  公开号：WO2017197051A1

  公开（公告）日：2017-11-16

  This invention provides amine-linked C3-glutarimide Degronimers and Degrons for therapeutic applications as described further herein, and methods of use and compositions thereof as well as methods for their preparation.

  这项发明提供了胺连接的C3-戊二酰亚胺Degronimers和Degrons，用于治疗应用，如本文进一步描述的，以及它们的使用方法、组合物以及它们的制备方法。
• 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。
• 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。
• Methods and Compositions Using Immunomodulatory Compounds for the Treatment and Management of Spirochete and Other Obligate Intracellular Bacterial Diseases
  申请人：Hensel Jennifer L.

  公开号：US20110184025A1

  公开（公告）日：2011-07-28

  Methods of treating, preventing and/or managing a spirochete and/or other obligate intracellular bacterial disease or disorder are disclosed. Specific methods encompass the administration of an immunomodulatory compound alone or in combination with a second active agent.

  本发明揭示了治疗、预防和/或管理螺旋体和/或其他依赖于细胞内的细菌性疾病或紊乱的方法。具体方法包括单独或与第二活性药物联合使用免疫调节化合物的给药。
• [EN] COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF ANDROGEN RECEPTOR PROTEIN<br/>[FR] COMPOSÉS ET PROCÉDÉS POUR LA DÉGRADATION CIBLÉE DE PROTÉINE DU RÉCEPTEUR DES ANDROGÈNES
  申请人：ARVINAS OPERATIONS INC

  公开号：WO2022087125A1

  公开（公告）日：2022-04-28

  Bifunctional compounds, which find utility as modulators of androgen receptor (AR), are described herein. In particular, the bifunctional compounds of the present disclosure contain on one end a moiety that binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds AR, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The bifunctional compounds of the present disclosure exhibit a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aberrant regulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

  本文描述了具有雄激素受体（AR）调节剂作用的双功能化合物。特别是，本公开的双功能化合物在一端含有结合到cereblon E3泛素连接酶的基团，在另一端含有结合到AR的基团，使得目标蛋白质靠近泛素连接酶以降解（和抑制）目标蛋白质。本公开的双功能化合物表现出与目标蛋白质降解/抑制相关的广泛的药理活性。使用本公开的化合物和组合物治疗或预防由于目标蛋白质异常调节而导致的疾病或障碍。