3-amino-1-methylpropylphosphonous acid | 103680-48-4

• 分子结构分类: 有机化合物 - 有机磷化合物
• 英文名称: 3-amino-1-methylpropylphosphonous acid
• 英文别名: (3-Amino-1-methylpropyl)phosphinic acid；4-Aminobutan-2-ylphosphinic acid；4-aminobutan-2-ylphosphinic acid
• CAS: 103680-48-4
• 化学式: C₄H₁₂NO₂P
• 分子量: 137.119
• InChiKey: RZRFDYWPDLJLMD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  8
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  69.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  正溴丁烷 、 3-amino-1-methylpropylphosphonous acid 在 盐酸 、 N,N-二异丙基乙胺 、 六甲基二硅氮烷 作用下， 生成 (3-amino-1(R,S)-methylpropyl)n-butylphosphinic acid hydrochloride
  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
• 作为产物：
  描述：

  ethyl 3-amino-1-methylpropyl(diethoxymethyl)phosphinate 在 盐酸 、 methyloxirane 作用下， 生成 3-amino-1-methylpropylphosphonous acid
  参考文献：
  名称：

  Diethoxymethylphosphonites and phosphinates. Intermediates for thesynthesis of α,β- and X aminoalkylphosphonous acids

  摘要：

  DOI：

  10.1016/s0040-4020(01)89240-1

文献信息

• Dingwall, J. G.; Ehrenfreund, J.; Hall, R. G., Phosphorus and Sulfur and the Related Elements, 1987, vol. 30, p. 571 - 574
  作者：Dingwall, J. G.、Ehrenfreund, J.、Hall, R. G.、Jack, J.

  DOI：——

  日期：——
• DINGWALL, J. G.;EHRENFREUND, J.;HALL, R. G., TETRAHEDRON, 45,(1989) N2, C. 3787-3808
  作者：DINGWALL, J. G.、EHRENFREUND, J.、HALL, R. G.

  DOI：——

  日期：——
• 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.
• Diethoxymethylphosphonites and phosphinates. Intermediates for thesynthesis of α,β- and X aminoalkylphosphonous acids
  作者：J.G. Dingwalla、J. Ehrenfreund、R.G. Hall

  DOI：10.1016/s0040-4020(01)89240-1

  日期：1989.1