n-butylphosphinic acid | 97040-21-6

• 分子结构分类: 有机化合物 - 有机磷化合物
• 英文名称: n-butylphosphinic acid
• 英文别名: butylphosphinic acid
• CAS: 97040-21-6
• 化学式: C₄H₁₁O₂P
• 分子量: 122.104
• InChiKey: MTWVYGIIHVUGNL-UHFFFAOYSA-N

物化性质

• 沸点：
  210.5±23.0 °C(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  7
• 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：
  43.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  氯甲酸乙酯 、 n-butylphosphinic acid 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以100%的产率得到ethyl butylphosphinate
  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：

  1-碘丁烷 在 ammonium hypophosphite 、 六甲基二硅氮烷 作用下， 生成 n-butylphosphinic acid
  参考文献：
  名称：

  由甲硅烷基亚膦酸酯和烷基卤化物合成烷基次膦酸

  摘要：

  通过在温和而灵活的条件下，将烷基卤加入甲硅烷基亚膦酸酯中，通过一锅法反应合成了单取代和二取代的次膦酸。

  DOI：

  10.1016/s0040-4039(00)73157-1

文献信息

• 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。
• Design, Synthesis, and Biological Evaluation of Phosphinopeptides against <i>Trypanosoma cruzi</i> Targeting Trypanothione Biosynthesis
  作者：Esteban L. Ravaschino、Roberto Docampo、Juan B. Rodriguez

  DOI：10.1021/jm050922i

  日期：2006.1.1

  the search for new safe chemotherapeutic and chemoprophylactic agents against American trypanosomiasis (Chagas's disease), a series of phosphinopeptides structurally related to glutathione was designed, synthesized, and evaluated as antiproliferative agents against the parasite responsible for this disease, the hemoflagellated protozoan Trypanosoma cruzi. The rationale for the synthesis of these compounds

  作为我们旨在寻找针对美国锥虫病（恰加斯氏病）的新型安全化学疗法和化学预防剂的项目的一部分，设计，合成并评估了一系列与谷胱甘肽结构相关的膦肽肽，作为针对引起该疾病的寄生虫的抗增殖剂，带鞭毛的原生动物克氏锥虫。支持这些化合物合成的基本原理是基于次膦酸部分的存在将模仿锥虫硫磷合酶（TryS），典型的C：N连接酶和这些药物的分子靶标的四面体过渡态。在设计的化合物中，有53种和54种是有效的生长抑制剂，可抑制成肌细胞中临床上更相关的T. cruzi（amastigotes）形式的生长。这些药物的功效与众所周知的抗寄生虫药WC-9的功效相当。在本研究中，作为药效基团的简单膦肽肽结构构成了直接优化药物开发的起点。
• Method for the production of alkylphosphonic acids, esters, and salts by oxidizing alkylphosphonous acids, and use thereof
  申请人：Hill Michael

  公开号：US09018413B2

  公开（公告）日：2015-04-28

  The invention relates to a method for producing monocarboxy-functionalized dialkylphosphinic acids, esters, and salts, characterized in that a) a phosphinic acid source (I) is reacted with olefins (IV) in the presence of a catalyst A to obtain an alkylphosphonous acid, the salt or ester (II) thereof, and b) the obtained alkylphosphonous acid, the salt or ester (II) thereof is reacted with an oxidizing agent or with an oxidizing agent and water or with oxygen and water in the presence of a catalyst B to obtain the alkylphosphonic acid derivative (III), wherein R1, R2, R3, R4 are identical or different from each other and independently represent, inter alia, H, C1-C18-alkyl, C6-C18-aryl, C6-C18-aralkyl, C6-C18-alkylaryl, X and Y are identical or different from each other and independently represent H, C1-C18-alkyl, C6-C18-aryl, C6-C18-aralkyl, C6-C18-alkylaryl, Mg, Ca, Al, Sb, Sn, Ge, Ti, Fe, Zr, Zn, Ce, Bi, Sr, Mn, Cu, Ni, Li, Na, K and/or a protonated nitrogenous base, and catalysts A and B are transition metals and/or transition metal compounds and/or catalyst systems composed of a transition metal and/or a transition metal compound and at least one ligand.

  该发明涉及一种生产单羧基功能化二烷基膦酸、酯和盐的方法，其特征在于a)在催化剂A的存在下，将膦酸源(I)与烯烃(IV)反应，得到一种烷基膦酸、其盐或酯(II)，b)将所得的烷基膦酸、其盐或酯(II)与氧化剂或与氧化剂和水或与氧气和水在催化剂B的存在下反应，得到烷基膦酸衍生物(III)，其中R1、R2、R3、R4相同或不同，独立表示H、C1-C18-烷基、C6-C18-芳基、C6-C18-芳基烷基、C6-C18-烷基芳基，X和Y相同或不同，独立表示H、C1-C18-烷基、C6-C18-芳基、C6-C18-芳基烷基、C6-C18-烷基芳基、Mg、Ca、Al、Sb、Sn、Ge、Ti、Fe、Zr、Zn、Ce、Bi、Sr、Mn、Cu、Ni、Li、Na、K和/或质子化的氮碱基，催化剂A和B是过渡金属和/或过渡金属化合物和/或由过渡金属和/或过渡金属化合物与至少一种配体组成的催化体系。
• Certain dioic acid derivatives useful as NAALADase inhibitors
  申请人：Guilford Pharmaceuticals Inc.

  公开号：US06025344A1

  公开（公告）日：2000-02-15

  The present disclosure relates to dipeptidase inhibitors, and more particularly, to novel phosphonate derivatives, hydroxyphosphinyl derivatives, and phosphoramidate derivatives that inhibit N-Acetylated .alpha.-Linked Acidic Dipeptidase (NAALADase) enzyme activity, pharmaceutical compositions comprising such derivatives, and methods of using such derivatives to inhibit NAALADase activity, and to treat prostate diseases, especially using the compounds of the present invention for the inhibition of the growth of prostate cancer cells.

  本公开涉及二肽酶抑制剂，更具体地说，涉及抑制N-乙酰化α-连接酸性二肽酶（NAALADase）酶活性的新磷酸酯衍生物、羟基磷酰衍生物和磷酰胺衍生物，包括这些衍生物的药物组合物，以及使用这些衍生物抑制NAALADase活性并治疗前列腺疾病的方法，尤其是使用本发明的化合物来抑制前列腺癌细胞的生长。
• Inhibitors of NAALADase enzyme activity
  申请人：Guilford Pharmaceuticals Inc.

  公开号：US06025345A1

  公开（公告）日：2000-02-15

  The present disclosure relates to dipeptidase inhibitors, and more particularly, to novel methods of using phosphonate derivatives, hydroxyphosphinyl derivatives, and phosphoramidate derivatives to inhibit N-Acetylated .alpha.-Linked Acidic Dipeptidase (NAALADase) enzyme activity, and to treat prostate diseases, especially using the compounds of the present invention for the inhibition of the growth of prostate cancer cells.

  本公开涉及二肽酶抑制剂，更特别地，涉及使用磷酸酯衍生物、羟基磷酰衍生物和磷酰胺衍生物的新方法来抑制N-乙酰化.α.-连接的酸性二肽酶（NAALADase）酶活性，并治疗前列腺疾病，特别是使用本发明的化合物抑制前列腺癌细胞生长。