diethoxymethyl(benzyl)phosphinic acid ethyl ester | 133457-79-1

• 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: diethoxymethyl(benzyl)phosphinic acid ethyl ester
• 英文别名: ethyl benzyl(diethoxymethyl)phosphinate；ethyl diethoxymethyl(benzyl)phosphinate；ethyl-P-benzyl-P-diethoxymethylphosphinate；[diethoxymethyl(ethoxy)phosphoryl]methylbenzene
• CAS: 133457-79-1
• 化学式: C₁₄H₂₃O₄P
• 分子量: 286.308
• InChiKey: FNAYWOPVPCSAIA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  19
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 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：

  diethoxymethyl(benzyl)phosphinic acid ethyl ester 在 盐酸 、 水 作用下， 反应 24.0h， 以100%的产率得到benzylphosphinic acid
  参考文献：
  名称：

  快速高效合成不对称次膦酸 R'P(O)OHR"

  摘要：

  已经评估了不对称次膦酸 R'P(O)OHR" 的新合成。第一个 P-C 键是由受保护的 H-次膦酸盐的碱促进 H-次膦酸盐烷基化形成的，处理起来更容易、更安全。为涉及 sila-Arbuzov 反应的第二个 P-C 键形成反应开发了一种一锅法。然后将该方法扩展到具有氨基官能团的二烷基次膦酸的合成。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

  DOI：

  10.1002/ejoc.200900852
• 作为产物：
  描述：

  溴甲苯 、 ethyl diethoxymethylphosphinate 在 sodium 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以95%的产率得到diethoxymethyl(benzyl)phosphinic acid ethyl ester
  参考文献：
  名称：

  快速高效合成不对称次膦酸 R'P(O)OHR"

  摘要：

  已经评估了不对称次膦酸 R'P(O)OHR" 的新合成。第一个 P-C 键是由受保护的 H-次膦酸盐的碱促进 H-次膦酸盐烷基化形成的，处理起来更容易、更安全。为涉及 sila-Arbuzov 反应的第二个 P-C 键形成反应开发了一种一锅法。然后将该方法扩展到具有氨基官能团的二烷基次膦酸的合成。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

  DOI：

  10.1002/ejoc.200900852

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。
• Certain N-substituted-amino-alkane phosphinic acid derivatives having
  申请人：Ciba-Geigy Corporation

  公开号：US05229379A1

  公开（公告）日：1993-07-20

  Compounds having GABA.sub.B -antagonistic properties, for example those of formula I ##STR1## wherein one of the radicals R.sub.1, R.sub.2 and R.sub.3 is hydrogen or an aliphatic, cycloaliphatic, araliphatic or aromatic radical, another is hydrogen or, in the case of R.sub.1 or R.sub.2, hydroxy or, in the case of R.sub.1, halogen or, in the case of R.sub.2 together with R.sub.2 ', oxo, and the remaining radical is hydrogen, R.sub.1 ' is hydrogen or halogen, R.sub.2 ' is hydrogen, hydroxy or, together with R.sub.2, is oxo, R.sub.4 and R.sub.5 are hydrogen or R.sub.4 is an araliphatic or heteroarylaliphatic radical and R.sub.5 is hydrogen or an aliphatic radical, and R is an aliphatic, cycloaliphatic, cycloaliphatic-aliphatic, araliphatic, heteroarylaliphatic or aromatic radical having at least 2 carbon atoms or, when R.sub.1 is hydrogen or hydroxy, R.sub.2 is an aromatic radical and R.sub.1 ', R.sub.2 ' and R.sub.3 are hydrogen, R is methyl, and their pharmaceutically acceptable salts, can be used as active ingredients in medicaments for the treatment of epilepsies of the "petit mal" type. The invention relates also to novel compounds of formula I and processes for the preparation thereof.

  具有GABA.sub.B-拮抗性质的化合物，例如具有以下式I的化合物##STR1##其中R.sub.1、R.sub.2和R.sub.3中的一个是氢或脂肪族、环脂族、芳基脂肪族或芳香族基团，另一个是氢或在R.sub.1或R.sub.2的情况下是羟基或在R.sub.1的情况下是卤素或在R.sub.2与R.sub.2'一起是氧代基，其余基团是氢，R.sub.1'是氢或卤素，R.sub.2'是氢、羟基或与R.sub.2一起是氧代基，R.sub.4和R.sub.5是氢或R.sub.4是芳基脂肪族或杂环芳基脂肪族基团，R.sub.5是氢或脂肪族基团，R是至少有2个碳原子的脂肪族、环脂族、环脂族-脂肪族、芳基脂肪族、杂环芳基脂肪族或芳香族基团，当R.sub.1是氢或羟基时，R.sub.2是芳香族基团，且R.sub.1'、R.sub.2'和R.sub.3是氢时，R是甲基，以及它们的药学上可接受的盐，可用作治疗“小发作”型癫痫的药物中的活性成分。该发明还涉及具有式I的新化合物以及其制备方法。
• P-subsituted propane-phosphinic acid compounds
  申请人：Ciba-Geigy Corporation

  公开号：US05190934A1

  公开（公告）日：1993-03-02

  Compounds of the formula I ##STR1## wherein either R.sub.1 is halogen, R.sub.1 ' is halogen or hydrogen and R.sub.2 and R.sub.2 ' denote hydrogen or R.sub.1 and R.sub.1 ' represent hydrogen, R.sub.2 is an aliphatic or aromatic radical and R.sub.2 ' is hydroxy or R.sub.2 and R.sub.2 ' together represent oxo, and wherein R denotes an aliphatic, cycloaliphatic, cycloaliphatic-aliphatic or araliphatic radical having 2 or more carbon atoms or, if R.sub.1 and R.sub.1 ' denote hydrogen, R.sub.2 represents an aromatic radical and R.sub.2 ' is hydroxy, R represents methyl, and their salts are useful as nootropics, antidepressants and/or anxiolytics. The can be manufacture by replacing any group R.sub.5 by hydrogen and/or converting any group Z.sub.0 into amino in a compound of formula II ##STR2## in which R, R.sub.1, R.sub.1 ', R.sub.2 and R.sub.2 ' have their previous significances, Z represents a protected or latent amino group Z.sub.0 and R.sub.4 denotes hydrogen or a hyddroxy-protective group R.sub.5, and wherein amino as a constituent of R and/or hydroxy R.sub.2 ' or oxo R.sub.2 +R.sub.2 ' may be present in a temporarily protected form.

  式I的化合物##STR1##中，R.sub.1为卤素，R.sub.1'为卤素或氢，R.sub.2和R.sub.2'表示氢或R.sub.1和R.sub.1'代表氢，R.sub.2为脂肪族或芳香基团，R.sub.2'为羟基或R.sub.2和R.sub.2'一起表示羰基，其中R表示具有2个或更多碳原子的脂肪族、环脂肪族、环脂肪族-脂肪族或芳基脂肪族基团，或者如果R.sub.1和R.sub.1'表示氢，则R.sub.2表示芳香基团，R.sub.2'为羟基，R表示甲基，它们的盐可用作脑功能增强剂、抗抑郁剂和/或抗焦虑剂。可以通过将任何基团R.sub.5替换为氢和/或将任何基团Z.sub.0转化为氨基来制备，其中R、R.sub.1、R.sub.1'、R.sub.2和R.sub.2'具有其先前的含义，Z表示受保护或潜在的氨基团Z.sub.0，R.sub.4表示氢或羟基保护基团R.sub.5，氨基作为R的组分和/或羟基R.sub.2'或羰基R.sub.2+R.sub.2'可能以暂时受保护的形式存在于式II的化合物中##STR2##。
• N-substituted aminoalkanephosphinic acid derivatives, compositions
  申请人：Ciba-Geigy Corporation

  公开号：US05545631A1

  公开（公告）日：1996-08-13

  Compounds having GABA.sub.B -antagonistic properties, for example those of formula I ##STR1## wherein one of the radicals R.sub.1, R.sub.2 and R.sub.3 is hydrogen or an aliphatic, cycloaliphatic, araliphatic or aromatic radical, another is hydrogen or, in the case of R.sub.1 or R.sub.2, hydroxy or, in the case of R.sub.1, halogen or, in the case of R.sub.2 together with R.sub.2 ', oxo, and the remaining radical is hydrogen, R.sub.1 ' is hydrogen or halogen, R.sub.2 ' is hydrogen, hydroxy or, together with R.sub.2, is oxo, R.sub.4 and R.sub.5 are hydrogen or R.sub.4 is an araliphatic or heteroarylaliphatic radical and R.sub.5 is hydrogen or an aliphatic radical, and R is an aliphatic, cycloaliphatic, cycloaliphatic-aliphatic, araliphatic, heteroarylaliphatic or aromatic radical having at least 2 carbon atoms or, when R.sub.1 is hydrogen or hydroxy, R.sub.2 is an aromatic radical and R.sub.1 ', R.sub.2 ' and R.sub.3 are hydrogen. R is methyl, and their pharmaceutically acceptable salts, can be used as active ingredients in medicaments for the treatment of epilepsies of the "petit mal" type. The invention relates also to novel compounds of formula I and processes for the preparation thereof.

  具有GABA.sub.B-拮抗作用的化合物，例如式I的化合物##STR1## 其中R.sub.1，R.sub.2和R.sub.3中的一个是氢或脂肪族，环脂肪族，芳基脂肪族或芳香族基，另一个是氢或，在R.sub.1或R.sub.2的情况下，羟基或，在R.sub.1的情况下，卤素或，在R.sub.2与R.sub.2'的情况下，是氧代，其余基团是氢，R.sub.1'是氢或卤素，R.sub.2'是氢，羟基或与R.sub.2一起是氧代，R.sub.4和R.sub.5是氢或R.sub.4是芳基脂肪族或杂环芳基脂肪族基，R.sub.5是氢或脂肪族基，R是至少具有2个碳原子的脂肪族，环脂肪族，环脂肪族-脂肪族，芳基脂肪族，杂环芳基脂肪族或芳香族基，当R.sub.1为氢或羟基时，R.sub.2是芳基基团，R.sub.1'，R.sub.2'和R.sub.3为氢。其中R为甲基，以及它们的药学上可接受的盐，可用作治疗“小发作”型癫痫的药物的活性成分。本发明还涉及式I的新化合物及其制备方法。
• 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.