[(1S,2R,5S)-2-isopropyl-5-methylcyclohexyl] N-[(3S)-3-methyl-2,6-dioxo-3-piperidyl]carbamate

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: [(1S,2R,5S)-2-isopropyl-5-methylcyclohexyl] N-[(3S)-3-methyl-2,6-dioxo-3-piperidyl]carbamate
• 英文别名: [(1S,2R,5S)-5-methyl-2-propan-2-ylcyclohexyl] N-[(3S)-3-methyl-2,6-dioxopiperidin-3-yl]carbamate
• 化学式: C₁₇H₂₈N₂O₄
• 分子量: 324.42
• InChiKey: VRNBOBQYCFXDME-LKQDWFRTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  84.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [(1S,2R,5S)-2-isopropyl-5-methylcyclohexyl] N-[(3S)-3-methyl-2,6-dioxo-3-piperidyl]carbamate 在 氢溴酸 、 三甲基铝 、 potassium carbonate 、 N,N-二异丙基乙胺 作用下， 以 溶剂黄146 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 40.5h， 生成 (S)-3-(4-((4-((4-(2,4-difluorophenyl)piperazin-1-yl)methyl)benzyl)oxy)-1-oxoisoindolin-2-yl)-3-methylpiperidine-2,6-dione
  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
• 作为产物：
  描述：

  2-Benzylideneamino-2-methylglutarimide 在 盐酸 、 碳酸氢钠 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 5.0h， 生成 [(1S,2R,5S)-2-isopropyl-5-methylcyclohexyl] N-[(3S)-3-methyl-2,6-dioxo-3-piperidyl]carbamate
  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

• [EN] METHODS AND COMPOSITIONS USING 4-AMINO-2-(3-METHYL-2,6-DIOXOPIPERIDIN-3-YL)-ISOINDOLE-1-3-DIONE<br/>[FR] METHODES ET COMPOSITIONS UTILISANT 4-AMINO-2-(3-METHYL-2,6-DIOXOPIPERIDIN-3-YL)-ISOINDOLE-1-3-DIONE
  申请人：CELGENE CORP

  公开号：WO2006081251A2

  公开（公告）日：2006-08-03

  [EN] This invention relates to racemic and stereomerically pure 4-amino-2-(3-methyl- 2,6-dioxopiperidin-3-yl)-isoindole-1,3-dione, and prodrugs, salts and solvates thereof. Synthesis, methods of use, and pharmaceutical compositions of racemic and stereomerically pure 4-amino-2-(3-methyl-2,6-dioxo-piperidine-3-yl)-isoindole-1,3-dione, and prodrugs, salts and solvates thereof, are disclosed.
  [FR] Cette invention porte sur 4-amino-2-(3-methyl- 2,6-dioxopipéridin-3-yl)-isoindole-1,3-dione racémique et le stéréomériquement pure, et sur des promédicaments, des sels et des solvates de celle-ci. L'invention porte également sur la synthèse, sur des méthodes d'utilisation et sur des compositions pharmaceutiques de 4-amino-2-(3-methyl-2,6-dioxo-pipéridine-3-yl)-isoindole-1,3-dione racémique et stéréomériquement pure, et sur des promédicaments, des sels et des solvates de celle-ci.