2-hydroxy-2-phenyl-nonanoic acid amide | 63002-09-5

• 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: 2-hydroxy-2-phenyl-nonanoic acid amide
• 英文别名: 2-Hydroxy-2-phenylnonanamide
• CAS: 63002-09-5
• 化学式: C₁₅H₂₃NO₂
• 分子量: 249.353
• InChiKey: FXKCDILPUXRDAT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  18
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  63.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-hydroxy-2-phenyl-nonanoic acid amide 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 12.0h， 以87%的产率得到2-Hydroxy-2-phenyl-nonanoic acid
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationship Studies for Hydantoins and Analogues as Voltage-Gated Sodium Channel Ligands

  摘要：

  We previously developed a preliminary 3-D QSAR model for the binding of 14 hydantoins to the neuronal voltage-gated sodium channel; this model was successful in designing,an effective non-hydantoin ligand. To further understand structural features that result in optimum binding. here we synthesized a variety of compound classes and evaluated their binding affinities to the neuronal voltage-gated sodium channel using the [H-3]-batrachotoxinin A 20-a-benzoate ([H-3]BTX-B) binding assay. In order to understand the importance of the hydantoin ring for good sodium channel binding, related non-hydantoins such as hydroxy amides, oxazolidinediones, hydroxy acids, and amino acids were included. Two major conclusions were drawn: (1) The hydantoin ring is not critical for compounds with long alkyl side chains, but it is important for compounds with shorter side chains. (2) Relative to Khodorov's pharmacophore. which contains two hydrophobic regions, a third hydrophobic region may enhance binding to provide nanomolar inhibitors.

  DOI：

  10.1021/jm040077o
• 作为产物：
  描述：

  HEPTYLMAGNESIUM BROMIDE 在 potassium cyanide 、 18-冠醚-6 、 copper(I) bromide 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 30.25h， 生成 2-hydroxy-2-phenyl-nonanoic acid amide
  参考文献：
  名称：

  Block of human NaV1.5 sodium channels by novel α-hydroxyphenylamide analogues of phenytoin

  摘要：

  Voltage-gated sodium (Na) channels are a critical component of electrically excitable cells. Phenytoin (diphenylhydantoin, DPH) is an established sodium channel blocker and is a useful anticonvulsant and class 1b antiarrhythmic, and has been effectively used in the treatment of neuropathic pain. In this study, we have synthesized novel alpha-hydroxyphenylamide analogues of diphenylhydantoin and examined their ability to inhibit human Na(v)1.5 sodium channels expressed in Chinese Hamster Ovary (CHO-K1) cells. Phenyl ring substitutions were examined including para-methyl, para-fluoro, para-chloro, ortho-chloro and meta-chloro. We have found that phenyl ring substitutions with electron withdrawing properties resulted in compounds with greater activity. In comparison to diphenylhydantoin, the novel chloro-substituted (alpha-hydroxyphenylamide compounds produced as much as a 20-fold greater tonic and frequency-dependent blockade of Na(v)1.5 channels with an IC50 value of 14.5 muM. In addition, the chloro-substitutions have position specific state dependent blocking properties. The ortho-, ineta- and para-chloro substitutions have an 8-, 13- and 3-fold increased affinity for the inactivated state, respectively. Molecular modeling suggests that these differences in affinity are due to a direct interaction with the receptor. Comparing models of diphenylhydantoin to the novel alpha-hydroxyphenlyamide compound suggests that the increased activity may be due to an optimized phenyl ring position and increased molecular volume. This information may be useful in the development of more potent sodium channel blockers. (C) 2004 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.ejps.2004.01.004

文献信息

• Comparative Molecular Field Analysis of Hydantoin Binding to the Neuronal Voltage-Dependent Sodium Channel
  作者：Milton L. Brown、Congxiang C. Zha、Christopher C. Van Dyke、George B. Brown、Wayne J. Brouillette

  DOI：10.1021/jm980556l

  日期：1999.5.1

  general features that result in enhanced binding to the sodium channel. These include a preferred 5-phenyl ring orientation and a favorable steric effect resulting from the C5-alkyl chain. This model was then utilized to accurately predict literature sodium channel activities for hydantoins 14-20, which were not included in the training set. Finally the hydantoin CoMFA model was used to design the structurally

  比较分子场分析（CoMFA）是一种3-D QSAR技术，被广泛用于将生物学活性与空间和静电场中观察到的差异相关联。在这项研究中，CoMFA被用于基于14种结构多样的5-苯基乙内酰脲类似物生成一个模型，以描述对于增强钠通道结合很重要的结构和静电特征。通过体外钠通道结合活性的偏最小二乘（PLS）分析（表示为log IC50）和CoMFA描述符列进行关联，得出最终的非交叉验证模型，其训练集的R2 = 0.988。对于相同的训练集，最终的CoMFA模型比具有log P（R2 = 0.801）的简单关联更好地解释了数据。CoMFA的空间图和静电图描述了两个一般特征，这些特征可增强与钠通道的结合。这些包括优选的5-苯环取向和由C 5-烷基链产生的有利的空间效应。然后，利用该模型来准确预测乙内酰脲14-20的文献钠通道活性，但该组未包括在训练集中。最后，使用乙内酰脲CoMFA模型设计结构新颖的α-羟基-
• MASHEVSKAYA M. S.; VAXRIN M. I., IZV. VUZOV. XIMIYA I XIM. TEXNOL., 1979, 22, HO 11, 1323-1326
  作者：MASHEVSKAYA M. S.、 VAXRIN M. I.

  DOI：——

  日期：——
• MASHEVSKAYA M. S.; PETYUNIN P. A., IZV. VYSSH. UCHEB. ZAVEDENIJ, XIMIYA I XIM. TEXNOL., 1977, 20, HO 2, 174-+
  作者：MASHEVSKAYA M. S.、 PETYUNIN P. A.

  DOI：——

  日期：——
• NOVEL SODIUM CHANNEL BLOCKERS
  申请人：Brown Milton L.

  公开号：US20090030056A1

  公开（公告）日：2009-01-29

  The present invention is directed to novel phenyloin derivative compounds and the use of such compounds as sodium channel blockers. Such compositions have utility as anti-cancer agents and can be used to limit or prevent PCa growth and/or metastasis.
• US7439383B2
  申请人：——

  公开号：US7439383B2

  公开（公告）日：2008-10-21