(R)-2-((S)-2,2-二-5-OXO-1,3-二氧戊环-4-YL)-3-(萘-2-基)丙酸 | 198568-07-9

• 物质功能分类: 医药中间体 - 原料药中间体
• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 中文名称: (R)-2-((S)-2,2-二-5-OXO-1,3-二氧戊环-4-YL)-3-(萘-2-基)丙酸
• 英文名称: (R)-2-((S)-2,2-dimethyl-5-oxo-1,3-dioxolan-4-yl)-3-(naphthalen-2-yl)propanoic acid
• 英文别名: (2R)-2-[(4S)-2,2-dimethyl-5-oxo-1,3-dioxolan-4-yl]-3-naphthalen-2-ylpropanoic acid
• CAS: 198568-07-9
• 化学式: C₁₈H₁₈O₅
• 分子量: 314.338
• InChiKey: LFUFTVUAMDTQTF-CABCVRRESA-N

物化性质

• 沸点：
  517.5±30.0 °C(Predicted)
• 密度：
  1.271±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (R)-2-((S)-2,2-二-5-OXO-1,3-二氧戊环-4-YL)-3-(萘-2-基)丙酸 在 N-甲基吗啉 、 盐酸羟胺 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 2,N¹-dihydroxy-N⁴-(1-methylcarbamoyl-2-phenyl-ethyl)-3-naphthalen-2-ylmethyl-succinamide
  参考文献：
  名称：

  Selective inhibition of low affinity IgE receptor (CD23) processing: P1′ bicyclomethyl substituents

  摘要：

  Using a variety of alpha-hydroxy hydroxamic acid derivatives, the size and shape of the S-1' pocket for the CD23 processing metalloprotease has been explored. It has been demonstrated that a P-1' 2-naphthylmethyl group occupies most of the available space and gives excellent selectivity against fibroblast collagenase (matrix metalloproteinase-1, MMP-1) and other MMPs. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(99)00552-1
• 作为产物：
  描述：

  2-溴甲基萘 在 对甲苯磺酸 、 potassium hydroxide 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 26.0h， 生成 (R)-2-((S)-2,2-二-5-OXO-1,3-二氧戊环-4-YL)-3-(萘-2-基)丙酸
  参考文献：
  名称：

  Optimization of Peptide Hydroxamate Inhibitors of Insulin-Degrading Enzyme Reveals Marked Substrate-Selectivity

  摘要：

  Insulin-degrading enzyme (IDE) is an atypical zinc-metallopeptidase that degrades insulin and the amyloid ss-protein and is strongly implicated in the pathogenesis of diabetes and Alzheimer's disease. We recently developed the first effective inhibitors of IDE, peptide hydroxamates that, while highly potent and selective, are relatively large (MW > 740) and difficult to synthesize. We present here a facile synthetic route that yields enantiomerically pure derivatives comparable in potency to the parent compounds. Through the generation of truncated variants, we identified a compound with significantly reduced size (MW = 455.5) that nonetheless retains good potency (k(i), = 78 +/- 11 nM) and selectivity for IDE. Notably, the potency of these inhibitors was found to vary as much as 60-fold in a substrate-specific manner, an unexpected finding for active site-directed inhibitors. Collectively, our findings demonstrate that potent, small-molecule IDE inhibitors can be developed that, in certain instances, can be highly substrate selective.

  DOI：

  10.1021/jm301280p

文献信息

• Optimization of Peptide Hydroxamate Inhibitors of Insulin-Degrading Enzyme Reveals Marked Substrate-Selectivity
  作者：Samer O. Abdul-Hay、Amy L. Lane、Thomas R. Caulfield、Clémence Claussin、Juliette Bertrand、Amandine Masson、Shakeel Choudhry、Abdul H. Fauq、Guhlam M. Maharvi、Malcolm A. Leissring

  DOI：10.1021/jm301280p

  日期：2013.3.28

  Insulin-degrading enzyme (IDE) is an atypical zinc-metallopeptidase that degrades insulin and the amyloid ss-protein and is strongly implicated in the pathogenesis of diabetes and Alzheimer's disease. We recently developed the first effective inhibitors of IDE, peptide hydroxamates that, while highly potent and selective, are relatively large (MW > 740) and difficult to synthesize. We present here a facile synthetic route that yields enantiomerically pure derivatives comparable in potency to the parent compounds. Through the generation of truncated variants, we identified a compound with significantly reduced size (MW = 455.5) that nonetheless retains good potency (k(i), = 78 +/- 11 nM) and selectivity for IDE. Notably, the potency of these inhibitors was found to vary as much as 60-fold in a substrate-specific manner, an unexpected finding for active site-directed inhibitors. Collectively, our findings demonstrate that potent, small-molecule IDE inhibitors can be developed that, in certain instances, can be highly substrate selective.
• Selective inhibition of low affinity IgE receptor (CD23) processing: P1′ bicyclomethyl substituents
  作者：Stuart Bailey、Brian Bolognese、Andrew Faller、Pearl Louis-Flamberg、David T. MacPherson、Ruth J. Mayer、Lisa A. Marshall、Peter H. Milner、Jayshree Mistry、David G. Smith、John G. Ward

  DOI：10.1016/s0960-894x(99)00552-1

  日期：1999.11

  Using a variety of alpha-hydroxy hydroxamic acid derivatives, the size and shape of the S-1' pocket for the CD23 processing metalloprotease has been explored. It has been demonstrated that a P-1' 2-naphthylmethyl group occupies most of the available space and gives excellent selectivity against fibroblast collagenase (matrix metalloproteinase-1, MMP-1) and other MMPs. (C) 1999 Elsevier Science Ltd. All rights reserved.