ethyl 2-phenylethyl-H-phosphinate | 86552-39-8

• 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: ethyl 2-phenylethyl-H-phosphinate
• 英文别名: (2-phenylethyl)phosphinic acid, ethyl ester
• CAS: 86552-39-8
• 化学式: C₁₀H₁₅O₂P
• 分子量: 198.202
• InChiKey: RMFZVGFYSQQTHT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.74
• 重原子数：
  13.0
• 可旋转键数：
  5.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  26.3
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  ethyl 2-phenylethyl-H-phosphinate 在 sodium hydroxide 作用下， 生成 (2-phenylethyl)phosphinic acid
  参考文献：
  名称：

  Phosphonamidate compounds

  摘要：

  式中X为氨基酸或酯。这些化合物具有抑制血管紧张素转化酶和脑啡肽酶的活性。因此它们可用作降压和镇痛剂。

  公开号：

  US04432972A1
• 作为产物：
  描述：

  magnesium,ethylbenzene,bromide 在 水 、 silica gel 作用下， 以 四氢呋喃 、 正己烷 、 乙酸乙酯 为溶剂， 生成 ethyl 2-phenylethyl-H-phosphinate
  参考文献：
  名称：

  通过 SiO2 促进的水解从 P(OR)3 或 ClP(OR)2 轻松合成 H-次膦酸盐

  摘要：

  H-磷酸盐代表一类有价值的有机磷结构单元和催化配体。现有的合成方法通常与强酸的使用、中间体精细处理的需要以及仅引入对芳基的限制有关。在对粗 R'P(OR) 2中间体的色谱处理过程中观察到的意外 SiO 2促进的水解进行全面研究后，我们开发了一种极其简单且通用的合成路线，从市售格氏试剂和 P （或） 3 .另一种方法涉及使用 ClP(OR) 2代替 P(OR) 3 ，这被证明是制备带有大体积邻位取代基序的空间位阻 ArMgBr 底物的有价值的策略。因此，使用该实用方案以中等至高产率获得了 36 种结构不同的 P-(环)烷基和 P-(杂)芳基H-次膦酸盐库。此外，还检查了CuCl 2介导的P(O)–H键衍生，导致以接近定量的产率形成相应的EtOPhP(O)–X (X = O, N, S)化合物。

  DOI：

  10.1021/acs.joc.4c00760

文献信息

• Discovery of Potent, Selective, Orally Active, Nonpeptide Inhibitors of Human Mast Cell Chymase
  作者：Michael N. Greco、Michael J. Hawkins、Eugene T. Powell、Harold R. Almond,、Lawrence de Garavilla、Jeffrey Hall、Lisa K. Minor、Yuanping Wang、Thomas W. Corcoran、Enrico Di Cera、Angelene M. Cantwell、Savvas N. Savvides、Bruce P. Damiano、Bruce E. Maryanoff

  DOI：10.1021/jm0700619

  日期：2007.4.1

  identified as a new structural motif for obtaining potent inhibitors of human mast cell chymase. For example, 1-naphthyl derivative 5f had an IC50 value of 29 nM and (E)-styryl derivative 6g had an IC50 value of 3.5 nM. An X-ray structure for 5f.chymase revealed key interactions within the enzyme active site. Compound 5f was selective for inhibiting chymase versus eight serine proteases. Compound 6h

  一系列的β-羧酰胺基膦酸（in）酸（2）被确定为获得有效的人肥大细胞糜酶抑制剂的新结构基序。例如，1-萘基衍生物5f的IC 50值为29nM，（E）-苯乙烯基衍生物6g的IC 50值为3.5nM。5f.chymase的X射线结构揭示了酶活性位点内的关键相互作用。与8种丝氨酸蛋白酶相比，化合物5f对抑制糜蛋白酶具有选择性。化合物6h在大鼠中可口服生物利用（F ＝ 39％），并且在仓鼠炎症模型中口服有效。
• Novel inhibitors of chymase
  申请人：Hawkins Michael J.

  公开号：US20100048513A1

  公开（公告）日：2010-02-25

  The present invention is directed to a compound of formula (I), methods for preparing these compounds, compositions, intermediates and derivatives thereof, and methods for treating inflammatory and serine protease mediated disorders.

  本发明涉及一种式（I）的化合物，制备这些化合物的方法，组合物，中间体和衍生物，以及治疗炎症和丝氨酸蛋白酶介导的疾病的方法。
• NOVEL INHIBITORS OF CHYMASE
  申请人：Hawkins Michael J.

  公开号：US20120022022A1

  公开（公告）日：2012-01-26

  The present invention is directed to a compound of formula (I), methods for preparing these compounds, compositions, intermediates and derivatives thereof, and methods for treating inflammatory and serine protease mediated disorders.

  本发明涉及一种化合物，其化学式为（I），以及制备这些化合物的方法，组合物，中间体和衍生物，以及用于治疗炎症和丝氨酸蛋白酶介导的疾病的方法。
• 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.
• US7459444B2
  申请人：——

  公开号：US7459444B2

  公开（公告）日：2008-12-02