ethyl-3-aminopropyl(tetrahydrofuran-2-yl)phosphinate | 123691-87-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氧唑烯
• 英文名称: ethyl-3-aminopropyl(tetrahydrofuran-2-yl)phosphinate
• 英文别名: 3-[ethoxy(oxolan-2-yl)phosphoryl]propan-1-amine
• CAS: 123691-87-2
• 化学式: C₉H₂₀NO₃P
• 分子量: 221.236
• InChiKey: GGVWFEJRAHBZCE-UHFFFAOYSA-N

物化性质

• 沸点：
  324.9±52.0 °C(Predicted)
• 密度：
  1.09±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  14
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  61.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl-3-aminopropyl(tetrahydrofuran-2-yl)phosphinate 在 三甲基溴硅烷 、 水 作用下， 生成 (3-aminopropyl)<(R,S)-tetrahydrofuran-2-yl>phosphinic acid hydrobromide
  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 (tetrahydrofuran-2-yl)phosphinate 在 镍 氨 、 氢气 、 sodium ethanolate 作用下， 以 乙醇 为溶剂， 10.0~75.0 ℃ 、10.0 MPa 条件下， 反应 5.0h， 生成 ethyl-3-aminopropyl(tetrahydrofuran-2-yl)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

• Substituted propane-phosphinic acid compounds
  申请人：Ciba-Geigy Corporation

  公开号：US05064819A1

  公开（公告）日：1991-11-12

  Compounds of the formula I ##STR1## wherein R denotes an aliphatic, cycloaliphatic, cycloaliphatic-aliphatic or araliphatic radical having 2 or more carbon atoms, and wherein one of the groups R.sup.1, R.sup.2 and R.sup.3 represents hydrogen or an aliphatic, cycloaliphatic, araliphatic or aromatic radical, another one of R.sup.1, R.sup.2 and R.sup.3 is hydrogen or, in the case of R.sup.1 and R.sup.2, is hydroxy, and the remaining one of R.sup.1, R.sup.2 and R.sup.3 is hydrogen, or wherein R denotes methyl, R.sub.1 denotes hydrogen or hydroxy, R.sub.2 denotes an aromatic radical and R.sub.3 represents hydrogen, and their salts have GABA.sub.B -antagonistic properties and can be used as GABA.sub.B -antagonists. They are obtained when in a compound of formula II ##STR2## in which R, R.sup.1, R.sup.2 and R.sup.3 have their previous significances, Z represents --NH.sub.2 and R.sup.4 denotes a hydroxy-protective group R.sup.5 or, when R.sup.1 and R.sup.3 denote hydrogen and R.sup.2 denotes hydrogen or alkyl, denotes an alkali metal or ammonium ion R.sup.6, or Z represents a protected or latent amino group Z.sup.0 and R.sup.4 denotes hydrogen or a hydroxy-protective group R.sup.5, any group R.sup.5 or R.sup.6 is replaced by hydrogen, and/or any group Z.sup.0 is converted into --NH.sub.2.

  公式I的化合物##STR1##其中R表示具有2个或更多碳原子的脂肪族、环脂族、环脂族-脂肪族或芳基脂肪基，其中R.sup.1、R.sup.2和R.sup.3中的一个代表氢或脂肪族、环脂族、芳基脂肪基或芳香族基，R.sup.1、R.sup.2和R.sup.3中的另一个是氢或在R.sup.1和R.sup.2的情况下是羟基，而R.sup.1、R.sup.2和R.sup.3中的剩余一个是氢，或者R表示甲基，R.sub.1表示氢或羟基，R.sub.2表示芳基，R.sub.3表示氢，它们的盐具有GABA.sub.B-拮抗性质，可用作GABA.sub.B-拮抗剂。当在公式II的化合物中获得它们##STR2##其中R、R.sup.1、R.sup.2和R.sup.3具有其先前的含义，Z表示--NH.sub.2，R.sup.4表示羟基保护基R.sup.5或者当R.sup.1和R.sup.3表示氢且R.sup.2表示氢或烷基时，表示碱金属或铵离子R.sup.6，或者Z表示受保护或潜在的氨基Z.sup.0且R.sup.4表示氢或羟基保护基R.sup.5，任何一个R.sup.5或R.sup.6基团被氢取代，和/或任何一个Z.sup.0基团被转化为--NH.sub.2。
• Novel substituted propane phosphinic acid compounds
  申请人：CIBA-GEIGY AG

  公开号：EP0319482A2

  公开（公告）日：1989-06-07

  Compounds of the formula I wherein R denotes an aliphatic, cycloaliphatic, cycloaliphatic-aliphatic or araliphatic radical having 2 or more carbon atoms, and wherein one of the groups R¹, R² and R³ represents hydrogen or an aliphatic, cyclo­aliphatic, araliphatic or aromatic radical, another one of R¹, R² and R³ is hydrogen or, in the case of R¹ and R², is hydroxy, and the remaining one of R¹, R² and R³ is hydrogen, and their salts have GABAB-anta­gonistic properties and can be used as GABAB-antagonists. They are obtained when in a compound of formula II in which R, R¹, R² and R³ have their previous significances, Z represents -NH₂ and R⁴ denotes a hydroxy-protective group R⁵ or, when R¹ and R³ denote hydrogen and R² denotes hydrogen or alkyl, denotes an alkali metal or ammonium ion R⁶, or Z represents a protected or latent amino group Zo and R⁴ denotes hydrogen or a hydroxy-protective group R⁵, any group R⁵ or R⁶ is replaced by hydrogen, and/or any group Zo is converted into -NH₂.

  式 I 的化合物 其中 R 表示具有 2 个或 2 个以上碳原子的脂肪族、环脂族、环脂族-脂肪族或芳香族基团，其中基团 R¹、R² 和 R³ 中的一个代表氢或脂肪族、环脂族、芳香族或芳香族基团、R¹、R² 和 R³ 中的另一个为氢，或在 R¹ 和 R² 的情况下为羟基，R¹、R² 和 R³ 中的其余一个为氢，它们的盐具有 GABAB 拮抗特性，可用作 GABAB 拮抗剂。当式 II 的化合物中 其中 R、R¹、R² 和 R³ 具有其先前的意义，Z 表示-NH₂，R⁴ 表示羟基保护基团 R⁵，或当 R¹ 和 R³ 表示氢，R² 表示氢或烷基时，表示碱金属或铵离子 R⁶、或 Z 代表受保护或潜在的氨基 Zo，R⁴ 表示氢或羟基保护基团 R⁵，任何基团 R⁵ 或 R⁶ 被氢取代，和/或任何基团 Zo 转化为-NH₂。
• US5013863A
  申请人：——

  公开号：US5013863A

  公开（公告）日：1991-05-07
• US5051524A
  申请人：——

  公开号：US5051524A

  公开（公告）日：1991-09-24
• US5064819A
  申请人：——

  公开号：US5064819A

  公开（公告）日：1991-11-12