3-amino-3-methylpiperidine-2,6-dione

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 3-amino-3-methylpiperidine-2,6-dione
• 英文别名: α-methyl-α-aminoglutarimide；3-amino-3-methylpiperidin-2,6-dione
• 化学式: C₆H₁₀N₂O₂
• mdl: MFCD19204735
• 分子量: 142.158
• InChiKey: WTOYMYCNCNHMRN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.666
• 拓扑面积：
  72.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-amino-3-methylpiperidine-2,6-dione 在 4-二甲氨基吡啶 、 sodium acetate 、 potassium carbonate 、 溶剂黄146 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 34.0h， 生成 2-[2-[2-[2-[2-(3-methyl-2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-5-yl]oxyethoxy]ethoxy]ethoxy]ethyl 4-methylbenzenesulfonate
  参考文献：
  名称：

  [EN] INDAZOLE BASED COMPOUNDS AND ASSOCIATED METHODS OF USE
  [FR] COMPOSÉS A BASE D'INDAZOLE ET PROCÉDÉS D'UTILISATION ASSOCIÉS

  摘要：

  本文描述了作为亮氨酸富含重复激酶2（LRRK2）调节剂的双功能化合物。具体来说，本公开的异双功能化合物在一端含有结合到cereblon E3泛素连接酶的基团，另一端含有结合到LRRK2的基团，使得靶蛋白靠近泛素连接酶以实现靶蛋白的降解（和抑制）。本公开的异双功能化合物展示了与靶蛋白降解/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于靶蛋白异常调节而导致的疾病或障碍。

  公开号：

  WO2021194879A1

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。
• Isoindole-imide compounds and compositions comprising and methods of using the same
  申请人：Muller W. George

  公开号：US20070049618A1

  公开（公告）日：2007-03-01

  This invention relates to isoindole-imide compounds, and pharmaceutically acceptable salts, solvates, stereoisomers, and prodrugs thereof. Methods of use, and pharmaceutical compositions of these compounds are disclosed.

  这项发明涉及异吲哚-亚胺化合物，以及它们的药物可接受的盐、溶剂化物、对映异构体和前药。这些化合物的使用方法和药物组合物已经公开。
• [EN] BIFUNCTIONAL MOLECULES CONTAINING AN E3 UBIQUITINE LIGASE BINDING MOIETY LINKED TO A BCL6 TARGETING MOIETY<br/>[FR] MOLÉCULES BIFONCTIONNELLES CONTENANT UNE FRACTION DE LIAISON À L'UBIQUITINE LIGASE E3 LIÉE À UNE FRACTION CIBLANT BCL6
  申请人：ARVINAS OPERATIONS INC

  公开号：WO2021077010A1

  公开（公告）日：2021-04-22

  Bifunctional compounds, which find utility as modulators of B-cell lymphoma 6 protein (BCL6; target protein), are described herein. In particular, the bifunctional compounds of the present disclosure contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand that 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 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 aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

  本发明描述了双功能化合物，其作为B细胞淋巴瘤6蛋白（BCL6；靶蛋白）的调节剂。特别是，本发明中的双功能化合物一端含有与相应的E3泛素连接酶结合的Von Hippel-Lindau、cereblon、凋亡蛋白抑制剂或小鼠双分钟同源蛋白2的配体，另一端含有与靶蛋白结合的部分，使得靶蛋白被置于泛素连接酶附近，以促进靶蛋白的降解（和抑制）。本发明中的双功能化合物展示了与靶蛋白降解/抑制相关的广泛药理活性。可以通过本发明中的化合物和组合物治疗或预防由靶蛋白聚集或积累引起的疾病或失调。
• 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。
• 5H-THIOENO(3,4-c)PYRROLE-4,6-DIONE DERIVATIVES AND THEIR USE AS TUMOR NECROSIS FACTOR INHIBITORS
  申请人：ZHANG Hesheng

  公开号：US20080176900A1

  公开（公告）日：2008-07-24

  Taught are derivatives of 5H-thioeno(3,4- c )pyrrole-4,6-dione, their organic, and inorganic salts, methods of synthesis of these derivatives, and their application as active pharmaceutical-ingredients useful as inhibitors of TNFα, the derivative being represented by the general formula (I): in which R 1 represents H, C 1-6 alkyl, OR 4 , OC(O)R 5 , NO 2 , NHC(O)R 6 , or NR 7 R 8 ; R 2 represents H, a halogen, or C 1-6 alkyl; R 3 represents H, methyl, isopropyl, allyl, benzyl, CH 2 CO 2 (C 1-6 alkyl), or CH 2 (CH 2 ) n R 9 ; R 4 , R 5 , R 6 , R 7 , and R 8 each independently and at each occurrence represents H, or C 1-6 alkyl; R 9 represents H, C 1-6 alkyl, OH, OC 1-6 alkyl, NH 2 , NHC 1-6 alkyl, N(C 1-6 alkyl) 2 , or CO 2 (C 1-6 alkyl); and n represents 1, 2, 3, or 4.

  本发明涉及5H-噻烯[3,4-c]吡咯-4,6-二酮的衍生物，它们的有机盐和无机盐，这些衍生物的合成方法，以及它们作为抑制TNFα的活性药物成分的应用，所述衍生物由通式(I)表示： 其中R1代表H，C1-6烷基，OR4，OC(O)R5，NO2，NHC(O)R6或NR7R8；R2代表H，卤素或C1-6烷基；R3代表H，甲基，异丙基，烯丙基，苄基，CH2CO2(C1-6烷基)或CH2(CH2)nR9；R4、R5、R6、R7和R8每个独立地并且在每次出现时代表H或C1-6烷基；R9代表H，C1-6烷基，OH，OC1-6烷基，NH2，NHC1-6烷基，N(C1-6烷基)2或CO2(C1-6烷基)；n代表1、2、3或4。