3-hydroxy-4-(3-methylphenoxy)benzoic acid | 1435949-37-3

• 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: 3-hydroxy-4-(3-methylphenoxy)benzoic acid
• 英文别名: 3-Hydroxy-4-(3-methylphenoxy)benzoic Acid
• CAS: 1435949-37-3
• 化学式: C₁₄H₁₂O₄
• 分子量: 244.247
• InChiKey: UJEGPWILRQVWSF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-{(2S)-4-[(2S)-2-amino-3-methylbutyl]-2-methylpiperazin-1-yl}phenol 、 3-hydroxy-4-(3-methylphenoxy)benzoic acid 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 生成 3-hydroxy-N-[(2S)-1-[(3S)-4-(3-hydroxyphenyl)-3-methylpiperazin-1-yl]-3-methylbutan-2-yl]-4-(3-methylphenoxy)benzamide
  参考文献：
  名称：

  Discovery of N-{4-[(3-Hydroxyphenyl)-3-methylpiperazin-1-yl]methyl-2-methylpropyl}-4-phenoxybenzamide Analogues as Selective Kappa Opioid Receptor Antagonists

  摘要：

  There is continuing interest in the discovery and development of new kappa opioid receptor antagonists. We recently reported that N-substituted 3-methyl-4-(3-hydroxyphenyl)piperazines were a new class of opioid receptor antagonists. In this study, we report the syntheses of two piperazine JDTic-like analogues. Evaluation of the two compounds in an in vitro [S-35]GTP gamma S binding assay showed that neither compound showed the high potency and kappa opioid receptor selectivity of JDTic. A library of compounds using the core scaffold 21 was synthesized and tested for their ability to inhibit [S-35]GTP gamma S binding stimulated by the selective kappa opioid agonist U69,593. These studies led to N-[(1S)-1-{[(3S)-4-(3-hydroxyphenyl)-3-methylpiperazin-1-yl]methyll-2-methylpropyl]-4-phenoxybenzamide (11a), a compound that showed good kappa opioid receptor antagonist properties. An SAR study based on 11a provided 28 novel analogues. Evaluation of these 28 compounds in the [S-35]GTP gamma S binding assay showed that several of the analogues were potent and selective kappa opioid receptor antagonists.

  DOI：

  10.1021/jm400275h
• 作为产物：
  描述：

  香草酸甲酯 在 copper(I) oxide 、 水 、 氢溴酸 、 lithium hydroxide 作用下， 以 1,4-二氧六环 、 2,4,6-三甲基吡啶 、 溶剂黄146 为溶剂， 反应 5.0h， 生成 3-hydroxy-4-(3-methylphenoxy)benzoic acid
  参考文献：
  名称：

  1-substituted 4-arylpiperazine as kappa opioid receptor antagonists

  摘要：

  提供的化合物由以下公式表示：其中R、Y3、R1、R2、R3、R4、R6、G、R7、E1、E2、A、B、W、X、Y和Z的定义如下。

  公开号：

  US09512105B2
• 作为试剂：
  描述：

  3-methoxy-4-(3-methylphenoxy)benzoic acid 、 溶剂黄146 在 3-hydroxy-4-(3-methylphenoxy)benzoic acid 、 二氯甲烷 、 甲苯 作用下， 以 氢溴酸 为溶剂， 反应 4.0h， 以afforded 18i (99+%)的产率得到3-hydroxy-4-(3-methylphenoxy)benzoic acid
  参考文献：
  名称：

  1-SUBSTITUTED 4-ARYLPIPERAZINE AS KAPPA OPIOID RECEPTOR ANTAGONISTS

  摘要：

  提供的化合物由以下公式表示：其中R，Y3，R1，R2，R3，R4，R6，G，R7，E1，E2，A，B，W，X，Y和Z的定义如下。

  公开号：

  US20150005315A1

文献信息

• [EN] 1-SUBSTITUTED 4-ARYLPIPERAZINE AS KAPPA OPIOID RECEPTOR ANTAGONISTS<br/>[FR] 4-ARYLPIPÉRAZINE 1-SUBSTITUÉ À TITRE D'ANTAGONISTE DU RÉCEPTEUR OPIOÏDE KAPPA
  申请人：RES TRIANGLE INST

  公开号：WO2013086496A3

  公开（公告）日：2014-12-18
• US9512105B2
  申请人：——

  公开号：US9512105B2

  公开（公告）日：2016-12-06
• Discovery of <i>N</i>-{4-[(3-Hydroxyphenyl)-3-methylpiperazin-1-yl]methyl-2-methylpropyl}-4-phenoxybenzamide Analogues as Selective Kappa Opioid Receptor Antagonists
  作者：Chad M. Kormos、Chunyang Jin、Juan Pablo Cueva、Scott P. Runyon、James B. Thomas、Lawrence E. Brieaddy、S. Wayne Mascarella、Hernán A. Navarro、Brian P. Gilmour、F. Ivy Carroll

  DOI：10.1021/jm400275h

  日期：2013.6.13

  There is continuing interest in the discovery and development of new kappa opioid receptor antagonists. We recently reported that N-substituted 3-methyl-4-(3-hydroxyphenyl)piperazines were a new class of opioid receptor antagonists. In this study, we report the syntheses of two piperazine JDTic-like analogues. Evaluation of the two compounds in an in vitro [S-35]GTP gamma S binding assay showed that neither compound showed the high potency and kappa opioid receptor selectivity of JDTic. A library of compounds using the core scaffold 21 was synthesized and tested for their ability to inhibit [S-35]GTP gamma S binding stimulated by the selective kappa opioid agonist U69,593. These studies led to N-[(1S)-1-[(3S)-4-(3-hydroxyphenyl)-3-methylpiperazin-1-yl]methyll-2-methylpropyl]-4-phenoxybenzamide (11a), a compound that showed good kappa opioid receptor antagonist properties. An SAR study based on 11a provided 28 novel analogues. Evaluation of these 28 compounds in the [S-35]GTP gamma S binding assay showed that several of the analogues were potent and selective kappa opioid receptor antagonists.
• 1-substituted 4-arylpiperazine as kappa opioid receptor antagonists
  申请人：RESEARCH TRIANGLE INSTITUTE

  公开号：US09512105B2

  公开（公告）日：2016-12-06

  Provided are compounds represented by the formula: where R, Y3, R1, R2, R3, R4, R6, G, R7, E1, E2, A, B, W, X, Y and Z are as defined herein.

  提供的化合物由以下公式表示：其中R、Y3、R1、R2、R3、R4、R6、G、R7、E1、E2、A、B、W、X、Y和Z的定义如下。
• 1-SUBSTITUTED 4-ARYLPIPERAZINE AS KAPPA OPIOID RECEPTOR ANTAGONISTS
  申请人：RESEARCH TRIANGLE INSTITUTE

  公开号：US20150005315A1

  公开（公告）日：2015-01-01

  Provided are compounds represented by the formula: where R, Y 3 , R 1 , R 2 , R 3 , R 4 , R 6 , G, R 7 , E 1 , E 2 , A, B, W, X, Y and Z are as defined herein.

  提供的化合物由以下公式表示：其中R，Y3，R1，R2，R3，R4，R6，G，R7，E1，E2，A，B，W，X，Y和Z的定义如下。