ethyl (3-amino-2(R)-hydroxypropyl)(cyclohexylmethyl)phosphinate | 848773-37-5

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: ethyl (3-amino-2(R)-hydroxypropyl)(cyclohexylmethyl)phosphinate
• 英文别名: O-ethyl (3-amino-(2R)-hydroxypropyl)(cyclohexylmethyl)phosphinate；(2R)-1-amino-3-[cyclohexylmethyl(ethoxy)phosphoryl]propan-2-ol
• CAS: 848773-37-5
• 化学式: C₁₂H₂₆NO₃P
• 分子量: 263.317
• InChiKey: YNSMUXOBANLSIJ-MTATWXBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  17
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  72.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl (3-amino-2(R)-hydroxypropyl)(cyclohexylmethyl)phosphinate 在 盐酸 、 水 作用下， 反应 4.0h， 生成 CGP 51176A
  参考文献：
  名称：

  Process for the preparation of 3-amino-2-hydroxypropylphosphinic acid derivatives

  摘要：

  本发明涉及一种制备式I的3-氨基-2-羟基丙基膦酸衍生物的方法，这些衍生物是有价值的药用活性成分，例如可用作抗抑郁药。该过程从式II的O-乙基膦酸酯出发，经过与六甲基二硅氮烷硅化后，通过与环氧氯丙烷和氨反应引入3-氨基-2-羟基丙基基团。

  公开号：

  US20050070507A1
• 作为产物：
  描述：

  O-ethyl (3-chloro-(2S)-trimethylsilyloxypropyl)(cyclohexylmethyl)phosphinate 在 氨 、 溶剂黄146 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 28.0h， 生成 ethyl (3-amino-2(R)-hydroxypropyl)(cyclohexylmethyl)phosphinate
  参考文献：
  名称：

  Phosphinic Acid Analogs of GABA. 2. Selective, Orally Active GABAB Antagonists

  摘要：

  In 1987, 25 years after the synthesis of the potent and selective GABA(B) agonist baclofen (1), Kerr et al.(5) described the first GABA(B) antagonist phaclofen 2. However, phaclofen and structurally similar derivatives 3-5 did not cross the blood-brain barrier and hence were inactive in vivo as central nervous system agents. As a consequence, the therapeutic potential of GABA(B) antagonists remained unclear. In exploring GABA and baclofen derivatives by replacing the carboxylic acid residue with various phosphinic acid groups, we discovered more potent and water soluble GABA(B) antagonists. Electrophysiological experiments in vivo demonstrated that some of the new compounds were capable of penetrating the blood-brain barrier after oral administration. Neurotransmitter release experiments showed that they interacted with several presynaptic GABA(B) receptor subtypes, enhancing the release of GABA, glutamate, aspartate, and somatostatin. The new GABA(B) antagonists interacted also with postsynaptic GABA(B) receptors, as they blocked late inhibitory postsynaptic potentials. They facilitated the induction of long-term potentiation in vitro and in, vivo, suggesting potential cognition enhancing effects. Fifteen compounds were investigated in Various memory and learning paradigms in rodents. Although several compounds were found to be active, only 10 reversed the age-related deficits of old rats in a multiple-trial one-way active avoidance test after chronic treatment. The cognition facilitating effects of 10 were confirmed in learning experiments in Rhesus monkeys. The novel GABA(B) antagonists showed also protective effects in various animal models of absence epilepsy.

  DOI：

  10.1021/jm00017a016

文献信息

• Process for the preparation of 3-amino-2-hydroxypropylphosphinic acid derivatives
  申请人：Huang Bao-Guo

  公开号：US20050070507A1

  公开（公告）日：2005-03-31

  The present invention relates to a process for the preparation of 3-amino-2-hydroxypropylphosphinic acid derivatives of the formula I, which are valuable pharmaceutical active ingredients and can be used, for example, as antidepressants. The process starts from O-ethyl phosphinates of the formula II into which, after silylation with hexamethyldisilazane, the 3-amino-2-hydroxypropyl moiety is introduced by reactions with epichlorohydrin and ammonia.

  本发明涉及一种制备式I的3-氨基-2-羟基丙基膦酸衍生物的方法，这些衍生物是有价值的药用活性成分，例如可用作抗抑郁药。该过程从式II的O-乙基膦酸酯出发，经过与六甲基二硅氮烷硅化后，通过与环氧氯丙烷和氨反应引入3-氨基-2-羟基丙基基团。
• Phosphinic Acid Analogs of GABA. 2. Selective, Orally Active GABAB Antagonists
  作者：Wolfgang Froestl、Stuart J. Mickel、Georg von Sprecher、Peter J. Diel、Roger G. Hall、Ludwig Maier、Dietrich Strub、Vito Melillo、Peter A. Baumann

  DOI：10.1021/jm00017a016

  日期：1995.8

  In 1987, 25 years after the synthesis of the potent and selective GABA(B) agonist baclofen (1), Kerr et al.(5) described the first GABA(B) antagonist phaclofen 2. However, phaclofen and structurally similar derivatives 3-5 did not cross the blood-brain barrier and hence were inactive in vivo as central nervous system agents. As a consequence, the therapeutic potential of GABA(B) antagonists remained unclear. In exploring GABA and baclofen derivatives by replacing the carboxylic acid residue with various phosphinic acid groups, we discovered more potent and water soluble GABA(B) antagonists. Electrophysiological experiments in vivo demonstrated that some of the new compounds were capable of penetrating the blood-brain barrier after oral administration. Neurotransmitter release experiments showed that they interacted with several presynaptic GABA(B) receptor subtypes, enhancing the release of GABA, glutamate, aspartate, and somatostatin. The new GABA(B) antagonists interacted also with postsynaptic GABA(B) receptors, as they blocked late inhibitory postsynaptic potentials. They facilitated the induction of long-term potentiation in vitro and in, vivo, suggesting potential cognition enhancing effects. Fifteen compounds were investigated in Various memory and learning paradigms in rodents. Although several compounds were found to be active, only 10 reversed the age-related deficits of old rats in a multiple-trial one-way active avoidance test after chronic treatment. The cognition facilitating effects of 10 were confirmed in learning experiments in Rhesus monkeys. The novel GABA(B) antagonists showed also protective effects in various animal models of absence epilepsy.