(S)-(+)-1-<2-ethyl>-3-piperidinecarboxylic acid | 143747-59-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (S)-(+)-1-<2-ethyl>-3-piperidinecarboxylic acid
• 英文别名: (3S)-1-[2-[bis(4-chlorophenyl)methoxy]ethyl]piperidine-3-carboxylic acid
• CAS: 143747-59-5
• 化学式: C₂₁H₂₃Cl₂NO₃
• 分子量: 408.325
• InChiKey: UFHSGXOXBRCZTN-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1,3-dioxoisoindolin-2-yl cyclopentanecarboxylate 、 (S)-(+)-1-<2-ethyl>-3-piperidinecarboxylic acid 在 Ni(bathophenanthroline)Cl₂*bis(N,N-dimethylformamide) 、 苯甲酸酐 、 lithium bromide 、 magnesium chloride 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 24.17h， 以3.6 mg的产率得到
  参考文献：
  名称：

  阴离子化学的激进方法：酮、醇和胺的合成

  摘要：

  历史上通过二电子、阴离子化学、酮、醇和胺进行访问对于有机合成的实践具有基础重要性。在将这项工作置于适当的历史背景下之后，本文报告了形成此类功能组的截然不同的方式的发展、全范围和机械图。因此，羧酸一旦转化为氧化还原活性酯 (RAE)，就可以用作形式上与其他羧酸衍生物（生产酮）、亚胺（生产苄胺）或醛（生产醇）的亲核偶联伙伴。这些反应一致温和，操作简单，并且在酮合成的情况下，范围很广（包括一些简化合成问题和平行合成的应用）。最后，

  DOI：

  10.1021/jacs.9b02238
• 作为产物：
  描述：

  3-哌啶甲酸乙酯 在 lithium hydroxide 、 potassium carbonate 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 79.0h， 生成 (S)-(+)-1-<2-ethyl>-3-piperidinecarboxylic acid
  参考文献：
  名称：

  Structure-activity studies on benzhydrol-containing nipecotic acid and guvacine derivatives as potent, orally-active inhibitors of GABA uptake

  摘要：

  The introduction of lipophilic groups onto the ring nitrogen of nipecotic acid and guvacine, two known GABA uptake inhibitors, afforded potent, orally-active anticonvulsant drugs. A series of compounds is reported which explores the structure-activity relationships (SAR) in this series. Among the areas explored: side-chain SAR (aromatic-, heterocyclic-, and tricyclic-containing side chains) and modifications to the tetrahydropyridine ring. The benzhydrol ether-containing side chains afforded the most potent compounds with several exhibiting in vitro IC50 values for GABA uptake of <1 muM (including 5, Table 1; 37, 43, Table IV; and 44, Table V). Compound 44 was selected for extensive evaluation and subsequently progressed to Phase 1 clinical trials with severe adverse effects seen after single dose administration to humans.

  DOI：

  10.1021/jm00100a032

文献信息

• A Radical Approach to Anionic Chemistry: Synthesis of Ketones, Alcohols, and Amines
  作者：Shengyang Ni、Natalia M. Padial、Cian Kingston、Julien C. Vantourout、Daniel C. Schmitt、Jacob T. Edwards、Monika M. Kruszyk、Rohan R. Merchant、Pavel K. Mykhailiuk、Brittany B. Sanchez、Shouliang Yang、Matthew A. Perry、Gary M. Gallego、James J. Mousseau、Michael R. Collins、Robert J. Cherney、Pavlo S. Lebed、Jason S. Chen、Tian Qin、Phil S. Baran

  DOI：10.1021/jacs.9b02238

  日期：2019.4.24

  Historically accessed through two-electron, anionic chemistry, ketones, alcohols, and amines are of foundational importance to the practice of organic synthesis. After placing this work in proper historical context, this Article reports the development, full scope, and a mechanistic picture for a strikingly different way of forging such functional groups. Thus, carboxylic acids, once converted to redox-active

  历史上通过二电子、阴离子化学、酮、醇和胺进行访问对于有机合成的实践具有基础重要性。在将这项工作置于适当的历史背景下之后，本文报告了形成此类功能组的截然不同的方式的发展、全范围和机械图。因此，羧酸一旦转化为氧化还原活性酯 (RAE)，就可以用作形式上与其他羧酸衍生物（生产酮）、亚胺（生产苄胺）或醛（生产醇）的亲核偶联伙伴。这些反应一致温和，操作简单，并且在酮合成的情况下，范围很广（包括一些简化合成问题和平行合成的应用）。最后，
• Structure-activity studies on benzhydrol-containing nipecotic acid and guvacine derivatives as potent, orally-active inhibitors of GABA uptake
  作者：Michael R. Pavia、Sandra J. Lobbestael、David Nugiel、Daniel R. Mayhugh、Vlad E. Gregor、Charles P. Taylor、Roy D. Schwarz、Laura Brahce、Mark G. Vartanian

  DOI：10.1021/jm00100a032

  日期：1992.10

  The introduction of lipophilic groups onto the ring nitrogen of nipecotic acid and guvacine, two known GABA uptake inhibitors, afforded potent, orally-active anticonvulsant drugs. A series of compounds is reported which explores the structure-activity relationships (SAR) in this series. Among the areas explored: side-chain SAR (aromatic-, heterocyclic-, and tricyclic-containing side chains) and modifications to the tetrahydropyridine ring. The benzhydrol ether-containing side chains afforded the most potent compounds with several exhibiting in vitro IC50 values for GABA uptake of <1 muM (including 5, Table 1; 37, 43, Table IV; and 44, Table V). Compound 44 was selected for extensive evaluation and subsequently progressed to Phase 1 clinical trials with severe adverse effects seen after single dose administration to humans.