3-phthalimidyl-piperidin-2-one | 42472-96-8

• 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: 3-phthalimidyl-piperidin-2-one
• 英文别名: N-(2-oxo-piperidin-3-yl)-phthalimide；(+/-)-3-phthalimidopiperidin-2-one；3-Phthalimidopiperidin-2-on；N-(2-Oxo-3-piperidyl)phthalimide；2-(2-oxopiperidin-3-yl)isoindole-1,3-dione
• CAS: 42472-96-8
• 化学式: C₁₃H₁₂N₂O₃
• 分子量: 244.25
• InChiKey: ZLYHJKFZUWNUEQ-UHFFFAOYSA-N

物化性质

• 沸点：
  490.9±38.0 °C(Predicted)
• 密度：
  1.393±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  66.5
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933790090

反应信息

• 作为反应物：
  描述：

  3-phthalimidyl-piperidin-2-one 在 ruthenium(IV) oxide 4-二甲氨基吡啶 、 sodium periodate 、 三氟乙酸 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 乙酸乙酯 、 乙腈 为溶剂， 反应 3.33h， 生成 3'-fluorothalidomide
  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：

  3-溴哌啶-2-酮 、 alkaline earth salt of/the/ methylsulfuric acid 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.17h， 以36%的产率得到3-phthalimidyl-piperidin-2-one
  参考文献：
  名称：

  Helm; Frankus; Friderichs, Arzneimittel-Forschung/Drug Research, 1981, vol. 31, # 6, p. 941 - 949

  摘要：

  DOI：
• 作为试剂：
  描述：

  2H-azepin-7-amine 、 盐酸 、 己内酰胺 、 potassium carbonate 、 3-氧代-3-(嘧啶-4-基)-丙酸乙酯 在 3,4,5,6-tetrahydro 、 3-phthalimidyl-piperidin-2-one 、 二氯甲烷 、 氯化钠 、 Sodium sulfate-III 、 乙醚 作用下， 以 乙醇 为溶剂， 反应 16.17h， 以to afford 36.4 g (28%) of pure product as a white-brown powder的产率得到2-pyrimidin-4-yl-7,8,9,10-tetrahydro-6H-pyrimido[1,2-a]azepin-4-one
  参考文献：
  名称：

  SUBSTITUTED HETEROARYL PYRIDOPYRIMIDONE DERIVATIVES

  摘要：

  本发明揭示和声明了由式(I)表示的吡啶酮衍生物，或其盐、溶剂或水合物。其中m、n、o、Y、Z、R1、R2、R3、R4、R5、R6和R7如本文所述。本发明还揭示了式(I)化合物的盐。本发明涉及一种药物，其包括所述衍生物或其盐作为活性成分，用于预防和/或治疗由GSK3β异常活性引起的神经退行性疾病，如阿尔茨海默病。

  公开号：

  US20090306088A1

文献信息

• TAU-PROTEIN TARGETING PROTACS AND ASSOCIATED METHODS OF USE
  申请人：Arvinas, Inc.

  公开号：US20180125821A1

  公开（公告）日：2018-05-10

  The present disclosure relates to bifunctional compounds, which find utility as modulators of tau protein. In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a VHL or cereblon ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds tau protein, such that tau protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of tau. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of tau protein. Diseases or disorders that result from aggregation or accumulation of tau protein are treated or prevented with compounds and compositions of the present disclosure.

  本公开涉及双功能化合物，其作为tau蛋白的调节剂具有实用性。具体而言，本公开涉及含有一端结合到E3泛素连接酶的VHL或cereblon配体，另一端结合到tau蛋白的双功能化合物，使得tau蛋白与泛素连接酶靠近，以实现tau蛋白的降解（和抑制）。本公开展示了与tau蛋白降解/抑制相关的广泛药理活性。本公开的化合物和组合物用于治疗或预防由tau蛋白聚集或积累导致的疾病或紊乱。
• COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF INTERLEUKIN-1 RECEPTOR-ASSOCIATED KINASE 4 POLYPEPTIDES
  申请人：Arvinas, Inc.

  公开号：US20190151295A1

  公开（公告）日：2019-05-23

  The present disclosure relates to bifunctional compounds, which find utility as modulators of Interleukin-1 Receptor-Associated Kinase 4 (IRAK-4); the target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hppel-Lindau, cereblon, ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

  本公开涉及双功能化合物，其作为白细胞介素-1受体相关激酶4（IRAK-4；目标蛋白）的调节剂具有实用性。具体而言，本公开涉及包含一端结合E3泛素连接酶的Von Hppel-Lindau、cereblon配体的双功能化合物，另一端结合目标蛋白的部分，使得目标蛋白靠近泛素连接酶以实现目标蛋白的降解（和抑制）。本公开展示了与目标蛋白的降解/抑制相关的广泛药理活性。本公开的化合物和组合物用于治疗或预防由目标蛋白聚集或积累导致的疾病或紊乱。
• 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。
• TETRAHYDRONAPHTHALENE AND TETRAHYDROISOQUINOLINE DERIVATIVES AS ESTROGEN RECEPTOR DEGRADERS
  申请人：Arvinas, Inc.

  公开号：US20180155322A1

  公开（公告）日：2018-06-07

  The present disclosure relates to bifunctional compounds, which find utility as modulators of estrogen receptor (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end at least one of a Von Hippel-Lindau ligand, a cereblon ligand, Inhibitors of Apoptosis Proteins ligand, mouse double-minute homolog 2 ligand, or a combination thereof, which binds to the respective E3 ubiquitin ligase, and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

  本公开涉及双功能化合物，这些化合物可用作雌激素受体（目标蛋白）的调节剂。特别是，本公开涉及包含在一段至少有一种Von Hippel-Lindau配体、一种cereblon配体、凋亡抑制蛋白配体、小鼠双分钟同源2配体或其组合的双功能化合物，这些配体与相应的E3泛素连接酶结合，在另一端有一个与目标蛋白结合的部分，使得目标蛋白被置于泛素连接酶附近，以实现目标蛋白的降解（和抑制）。本公开展示了与目标蛋白降解/抑制相关的广泛药理活性。可以通过本公开的化合物和组合物治疗或预防由目标蛋白聚集或积累引起的疾病或障碍。
• 3'-Fluoro-5'-hydroxythalidomide and derivatives thereof
  申请人：Takeuchi Yoshio

  公开号：US20090171093A1

  公开（公告）日：2009-07-02

  There are provided a novel 3′-fluoro-5′-hydroxythalidomide derivative and an optically active substance thereof A 3′-fluoro-5′-hydroxythalidomide derivative represented by the general formula [A]: wherein R 1 , R 2 and R 3 are each a hydrogen atom; and X is C═O, and an optically active substance thereof. As analogs of thalidomide, the 3′-fluoro-5′-hydroxythalidomide derivatives are useful in the treatment of erythema nodosum of Hansen's disease, prurigo, rheumatism, Crohn's disease, graft-versus-host disease, Behcet's disease, myeloma, aphtha ulcer and the like. Further, the 3′-fluoro-5′-hydroxythalidomide derivative is useful as a drug used for treatment of multiple myeloma, TNF-α related diseases and the like.

  提供了一种新型的3'-氟-5'-羟基沙利度胺衍生物及其光学活性物质。所述3'-氟-5'-羟基沙利度胺衍生物由通式[A]表示：其中R1、R2和R3分别是氢原子；X是C═O，及其光学活性物质。作为沙利度胺的类似物，3'-氟-5'-羟基沙利度胺衍生物在治疗汉森氏病的结节性红斑、瘙痒、风湿病、克罗恩病、移植物抗宿主病、贝赫切特病、多发性骨髓瘤、阿弗他溃疡等方面是有用的。此外，3'-氟-5'-羟基沙利度胺衍生物还用作治疗多发性骨髓瘤、TNF-α相关疾病等的药物。