2-Amino-2-methylglutarimide hydrochloride | 73839-06-2

• 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: 2-Amino-2-methylglutarimide hydrochloride
• 英文别名: 3-amino-3-methylpiperidine-2,6-dione HCl salt；3-methyl-2,6-dioxopiperidin-3-aminium chloride；3-amino-3-methylpiperidine-2,6-dione HCl；3-amino-3-methyl-piperidine-2,6-dione hydrochloride；3-amino-3-methylpiperidine-2,6-dione；(3-Methyl-2,6-dioxopiperidin-3-yl)azanium;chloride；(3-methyl-2,6-dioxopiperidin-3-yl)azanium;chloride
• CAS: 73839-06-2
• 化学式: C₆H₁₀N₂O₂*ClH
• 分子量: 178.619
• InChiKey: XABIMORGEXTPEY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.44
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  72.2
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-Amino-2-methylglutarimide hydrochloride 在 palladium on activated charcoal 氢气 、 溶剂黄146 作用下， 以 丙酮 为溶剂， 生成 1,3-dioxo-2-(3-methyl-2,6-dioxopiperidin-3-yl)-4-aminoisoindole
  参考文献：
  名称：

  Amino-substituted thalidomide analogs: Potent inhibitors of TNF-α production

  摘要：

  Thalidomide, (1), is a known inhibitor of TNF-alpha release in LPS stimulated human PBMC. Herein we describe the TNF-alpha inhibitory activity of amino substituted analogs of thalidomide (1) and its isoindolin-1-one analog, EM-12 (2). The 4-amino substituted analogs were found to be potent inhibitors of TNF-alpha release in LPS stimulated human PBMC. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(99)00250-4
• 作为产物：
  描述：

  2-Benzylideneamino-2-methylglutarimide 在 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 3.0h， 以96%的产率得到2-Amino-2-methylglutarimide hydrochloride
  参考文献：
  名称：

  Discovery of CRBN E3 Ligase Modulator CC-92480 for the Treatment of Relapsed and Refractory Multiple Myeloma

  摘要：

  Many patients with multiple myeloma (MM) initially respond to treatment with modern combination regimens including immunomodulatory agents (lenalidomide and pomalidomide) and proteasome inhibitors. However, some patients lack an initial response to therapy (i.e., are refractory), and although the mean survival of MM patients has more than doubled in recent years, most patients will eventually relapse. To address this need, we explored the potential of novel cereblon E3 ligase modulators (CELMoDs) for the treatment of patients with relapsed or refractory multiple myeloma (RRMM). We found that optimization beyond potency of degradation, including degradation efficiency and kinetics, could provide efficacy in a lenalidomide-resistant setting. Guided by both phenotypic and protein degradation data, we describe a series of CELMoDs for the treatment of RRMM, culminating in the discovery of CC-92480, a novel protein degrader and the first CELMoD to enter clinical development that was specifically designed for efficient and rapid protein degradation kinetics.

  DOI：

  10.1021/acs.jmedchem.9b01928

文献信息

• 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。
• [EN] BROMODOMAIN TARGETING DEGRONIMERS FOR TARGET PROTEIN DEGRADATION<br/>[FR] DÉGRONIMÈRES CIBLANT UN BROMODOMAINE POUR LA DÉGRADATION DE PROTÉINES CIBLES
  申请人：C4 THERAPEUTICS INC

  公开号：WO2017197056A1

  公开（公告）日：2017-11-16

  This invention provides a Degronimer that has an E3 Ubiquitin Ligase targeting moiety (Degron) that can be linked to a Targeting Ligand for a bromodomain protein selected for in vivo degradation to achieve a therapeutic effect, and methods of use and compositions thereof as well as methods for their preparation.

  这项发明提供了一种Degronimer，它具有可与靶向配体连接的E3泛素连接酶靶向部位（Degron），该靶向配体选择用于体内降解溴结构域蛋白以实现治疗效果，并提供了使用方法、组合物以及它们的制备方法。
• Substituted 2(2,6-dioxopiperidin-3-yl)isoindolines
  申请人：Celgene Corporation

  公开号：US06335349B1

  公开（公告）日：2002-01-01

  Substituted 1,3-dioxo-2-(2,6-dioxopiperidin-3-yl)isoindolines and 1-oxo-2-(2,6-dioxo-piperidin-3-yl)isoindolines reduce the levels of TNF&agr; in a mammal and are useful in treating oncogenic conditions, inflammation, and autoimmune diseases. Typical embodiments are 1-oxo-2-(2,6-dioxo-3-methylpiperidin-3-yl)-4,5,6,7-tetrafluoroiso-indoline and 1,3-dioxo-2-(2,6-dioxo-3-methylpiperidin-3-yl)-4-aminoisoindoline.

  1,3-二氧代-2-(2,6-二氧代哌啶-3-基)异吲哚烷酮和1-氧代-2-(2,6-二氧代哌啶-3-基)异吲哚烷酮可降低哺乳动物体内TNF&agr;的水平，并可用于治疗肿瘤性疾病、炎症和自身免疫疾病。典型实施例包括1-氧代-2-(2,6-二氧代-3-甲基哌啶-3-基)-4,5,6,7-四氟异吲哚烷酮和1,3-二氧代-2-(2,6-二氧代-3-甲基哌啶-3-基)-4-氨基异吲哚烷酮。
• [EN] PRPK INHIBITORS<br/>[FR] INHIBITEURS DE PRPK
  申请人：DANA FARBER CANCER INST INC

  公开号：WO2022005961A1

  公开（公告）日：2022-01-06

  This disclosure relates to compounds of formula (I) as defined in the Specification. This disclosure also relates to methods of synthesizing the compound of formula (I) and using the compounds of formula (I) for treating a disease (e.g., cancer).

  本公开涉及到规范中定义的式(I)的化合物。本公开还涉及到合成式(I)化合物的方法以及利用式(I)化合物治疗疾病（例如癌症）的方法。