1,1-diethoxyethyl(cyclohexylmethyl)phosphinic acid ethyl ester | 153994-66-2

• 分子结构分类: 有机化合物 - 有机磷化合物 - 有机膦酸及其衍生物
• 英文名称: 1,1-diethoxyethyl(cyclohexylmethyl)phosphinic acid ethyl ester
• 英文别名: [1,1-diethoxyethyl(ethoxy)phosphoryl]methylcyclohexane
• CAS: 153994-66-2
• 化学式: C₁₅H₃₁O₄P
• 分子量: 306.382
• InChiKey: IMWDKPYYQXBYOC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  20
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1,1-diethoxyethyl(cyclohexylmethyl)phosphinic acid ethyl ester 在 三甲基氯硅烷 、 sodium ethanolate 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 27.0h， 生成 3-[Cyclohexylmethyl(ethoxy)phosphoryl]propanenitrile
  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：

  溴甲基环己烷 、 ethyl (1,1-diethoxyethyl)phosphinate 以 四氢呋喃 、 水 为溶剂， 生成 1,1-diethoxyethyl(cyclohexylmethyl)phosphinic acid ethyl ester
  参考文献：
  名称：

  N-aralkyl- and N-heteroaralkyl-aminoalkanephosphinic acids

  摘要：

  N-芳基和N-杂芳基氨基烷基膦酸的化学式I ##STR1## 其中R是至少有2个碳原子的脂肪烷基，环脂肪烷基，环脂肪烷基，芳基或杂芳基烷基基团，R.sub.1是氢或羟基，R.sub.2是通过自由或功能修饰的羧基取代的芳基或杂芳基烷基基团，该羧基直接或通过间隔连接，R.sub.3是氢，低碳基或R.sub.2基团，以及其盐具有有价值的智力增强和抗癫痫特性，并可用于制备智力增强或抗癫痫药物。

  公开号：

  US05332729A1

文献信息

• N-aralkyl-and N-heteroaralkyl-aminoalkanephosphinic acids
  申请人：Ciba-Geigy Corporation

  公开号：US05424441A1

  公开（公告）日：1995-06-13

  N-aralkyl- and N-heteroaralkyl-aminoalkanephosphinic acids of formula I ##STR1## wherein R is an aliphatic, cycloaliphatic, cycloaliphatic-aliphatic, araliphatic or heteroarylaliphatic radical having at least 2 carbon atoms, R.sub.1 is hydrogen or hydroxy, R.sub.2 is an araliphatic or heteroarylaliphatic radical substituted by free or functionally modified carboxy that is bonded directly or by way of a spacer, and R.sub.3 is hydrogen, lower alkyl or a group R.sub.2, and the salts thereof have valuable nootropic and anti-epileptic properties and can be used in the preparation of a nootropic or anti-epileptic medicament.

  式I中的N-烷基和N-杂环烷基-氨基烷基膦酸，其中R是具有至少2个碳原子的脂肪，环脂肪，环脂肪-脂肪，芳基脂肪或杂环芳基脂肪基团，R1是氢或羟基，R2是被自由或功能修饰的羧基取代的芳基脂肪或杂环芳基脂肪基团，该羧基直接或通过间隔物键合，R3是氢，低碳基或R2基团，以及其盐具有有价值的神经保护和抗癫痫特性，可用于制备神经保护或抗癫痫药物。
• Neue N-Aralkyl- und N-Heteroaralkylaminoalkanphosphinsäuren
  申请人：CIBA-GEIGY AG

  公开号：EP0569333A2

  公开（公告）日：1993-11-10

  N-Aralkyl- und N-Heteroaralkylaminoalkanphosphinsäuren der Formel I worin R einen aliphatischen, cycloaliphatischen, cycloaliphatisch-aliphatischen, araliphatischen oder heteroarylaliphatischen Rest mit mindestens 2 C-Atomen bedeutet, R1 Wasserstoff oder Hydroxy darstellt, R2 einen durch direkt oder über einen Spacer gebundenes, gegebenenfalls funktionell abgewandeltes Carboxy substituierten araliphatischen oder heteroarylaliphatischen Rest bedeutet und R3 Wasserstoff, Niederalkyl oder eine Gruppe R2 darstellt, und ihre Salze weisen wertvolle nootrope und antiepileptische Eigenschaften auf und können zur Herstellung eines nootropen oder antiepileptischen Arzneimittels verwendet werden.

  式 I 的 N-烷基和 N-杂烷基氨基烷酸 其中 R 是至少有 2 个碳原子的脂肪族、环脂族、环脂-脂肪族、芳脂族或杂芳脂族基，R1 是氢或羟基，R2 是直接键合或通过间隔键合的芳脂族或杂芳脂族基、R3 代表氢、低级烷基或基团 R2，它们的盐具有重要的促神智和抗癫痫特性，可用于制备促神智或抗癫痫药物。
• US5332729A
  申请人：——

  公开号：US5332729A

  公开（公告）日：1994-07-26
• US5424441A
  申请人：——

  公开号：US5424441A

  公开（公告）日：1995-06-13
• 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.