2-(4-hexylphenoxy)acetic acid | 3280-63-5

• 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-(4-hexylphenoxy)acetic acid
• CAS: 3280-63-5
• 化学式: C₁₄H₂₀O₃
• 分子量: 236.311
• InChiKey: LPYHDHGKBRMYBL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  17
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(4-hexylphenoxy)acetic acid 在 氯化亚砜 作用下， 以 苯 为溶剂， 反应 3.0h， 以96%的产率得到2-(4-hexylphenoxy)acetyl chloride
  参考文献：
  名称：

  恶二唑-异丙基酰胺作为有效的非共价蛋白酶体抑制剂

  摘要：

  对 50 000 ChemBridge 化合物库的筛选导致鉴定出恶二唑-异丙基酰胺1 (PI-1833)，其抑制胰凝乳蛋白酶样 (CT-L) 活性（IC 50 = 0.60 μM），对其他两种主要蛋白酶体几乎没有影响蛋白水解活性，胰蛋白酶样 (TL) 和谷氨酰肽水解样 (PGPH-L)。LC-MS/MS 和透析表明1是一种非共价且快速可逆的 CT-L 抑制剂。集中文库合成为11ad (PI-1840) 提供了 CT-L 活性 (IC 50= 27 纳米）。详细的 SAR 研究表明酰胺部分和两个苯环对修饰敏感。疏水性残基，如在对位丙基或丁基（未邻位或间位）的A环和一个的米-吡啶基团作为B环，显著提高活性。化合物11ad (IC 50 = 0.37 μM)在抑制完整 MDA-MB-468 人乳腺癌细胞中的 CT-L 活性和抑制其存活方面比1 (IC 50 = 3.5 μM)更有效。11ad的活

  DOI：

  10.1021/jm400221d
• 作为产物：
  描述：

  hex-5-en-3-yn-2-ol 在 镍 、 铜 、 锌 sodium hydroxide 、 磷酸 、 氢气 作用下， 生成 2-(4-hexylphenoxy)acetic acid
  参考文献：
  名称：

  Kakhniashvili,A.T.; Bugianishvili,D.Ya., Journal of Organic Chemistry USSR (English Translation), 1965, vol. 1, p. 1051 - 1054

  摘要：

  DOI：

文献信息

• Preparation and unique circular dichroism phenomena of urea-functionalized self-folding resorcinarenes bearing chiral termini through asymmetric hydrogen-bonding belts
  作者：Osamu Hayashida、Jun-ichi Ito、Shinji Matsumoto、Itaru Hamachi

  DOI：10.1039/b418880b

  日期：——

  Chiral macrocycles with eight (R)- and (S)-methylbenzylurea residues on the resorcinarene skeleton linked through a hexyl or dodecyl spacer having amide linkages have been prepared by the reactions of the corresponding octaamine derivative with (R)- and (S)-α-methylbenzylisocyanate, respectively. In chloroform, the urea-functionalized resorcinarenes with hexyl spacers form intramolecular hydrogen bonds by bundling the urea and amide residues in a cyclic fashion to give a self-folding cavitand. The urea and amide residues are cooperatively oriented in the same direction to result in asymmetric hydrogen-bonding belts. Unique circular dichroism (CD) bands are induced in the absorption wavelength ranges of the macrocyclic skeleton, caused by a chirality transmission from their chiral urea termini through hexyl spacers in the self-folded conformation. On the other hand, urea-functionalized resorcinarenes with a longer dodecyl spacer do not show such unique CD bands on the macrocycle, because of their weaker propensity for hydrogen bond formation. The characteristic CD bands of the urea-functionalized self-folding macrocycles disappeared upon complexation with anions such as chloride and bromide, reflecting breaking of the intramolecular hydrogen-bonding belts.

  通过相应的八胺衍生物分别与(R)-和(S)-α-甲基苄基异氰酸酯的反应，制备出了在间苯二酚骨架上有八个(R)-和(S)-甲基苄基脲残基的手性大环，这些残基通过具有酰胺键的己基或十二烷基间隔物连接。在氯仿中，带有己基间隔的脲官能化间苯二酚通过将脲和酰胺残基以环状方式捆绑在一起形成分子内氢键，从而得到一种自折叠空穴剂。脲和酰胺残基在同一方向上相互配合，形成不对称的氢键带。在大环骨架的吸收波长范围内，会出现独特的圆二色性（CD）带，这是由于在自折叠构象中，手性脲末端通过己基间隔产生了手性传递。另一方面，具有较长十二烷基间隔的脲官能化间苯二酚由于氢键形成的倾向性较弱，在大环上不会显示出这种独特的 CD 带。脲官能化自折叠大环与氯化物和溴化物等阴离子络合后，其特征性 CD 带消失，这反映了分子内氢键带的断裂。
• Urea-functionalized Resorcinarenes: Preparation, Self-folding, and Their CD Phenomena Caused by Chiral Urea Termini through Intramolecular Hydrogen Bonding Interactions
  作者：Osamu Hayashida、Jun-ichi Ito、Shinji Matsumoto、Itaru Hamachi

  DOI：10.1246/cl.2004.994

  日期：2004.8

  Self-folding resorcinarenes bearing optically active urea moieties showed unique circular dichroism (CD) phenomena on the macrocyclic skeleton, which were caused by their chiral urea termini through intramolecular hydrogen bonding interactions in chloroform. These characteristic CD bands were disappeared upon complexation with anions such as chloride and bromide.

  含有光学活性脲分子的自折叠间苯二酚在大环骨架上显示出独特的圆二色性（CD）现象，这是由其手性脲末端在氯仿中通过分子内氢键相互作用引起的。与氯化物和溴化物等阴离子络合后，这些特征性 CD 带消失了。
• PROTEASOME CHYMOTRYPSIN-LIKE INHIBITION USING PI-1833 ANALOGS
  申请人：H. Lee Moffitt Cancer Center and Research Institute, Inc

  公开号：US20140073650A1

  公开（公告）日：2014-03-13

  Focused library synthesis and medicinal chemistry on an oxadiazole-isopropylamide core proteasome inhibitor provided the lead compound that strongly inhibits CT-L activity. Structure activity relationship studies indicate the amide moiety and two phenyl rings are sensitive toward synthetic modifications. Only para-substitution in the A-ring was important to maintain potent CT-L inhibitory activity. Hydrophobic residues in the A-ring's para-position and meta-pyridyl group at the B-ring significantly improved inhibition. The meta-pyridyl moiety improved cell permeability. The length of the aliphatic chain at the para position of the A-ring is critical with propyl yielding the most potent inhibitor, whereas shorter (i.e. ethyl, methyl or hydrogen) or longer (i.e. butyl, propyl and hexyl) chains demonstrating progressively less potency. Introduction of a stereogenic center next to the ether moiety (i.e. substitution of one of the hydrogens by methyl) demonstrated chiral discrimination in proteasome CT-L activity inhibition (the S-enantiomer was 35-40 fold more potent than the R-enantiomer).

  聚焦于氧代二唑-异丙酰胺核心蛋白酶体抑制剂的合成和药物化学，提供了一种强烈抑制CT-L活性的先导化合物。结构活性关系研究表明，酰胺基团和两个苯环对合成修饰非常敏感。只有在A环上的对位取代对维持强效的CT-L抑制活性至关重要。A环对位的疏水基团和B环的间吡啶基团显著提高了抑制作用。间吡啶基团提高了细胞渗透性。A环对位的脂肪链长度是关键，丙基产生了最有效的抑制剂，而较短（即乙基，甲基或氢）或较长（即丁基，异丙基和己基）的链逐渐表现出较少的效力。在醚基团旁引入一个立体异构中心（即将一个氢原子取代为甲基）表明在蛋白酶体CT-L活性抑制中具有手性歧视（S-对映体比R-对映体更有效，效力提高了35-40倍）。
• Proteasome chymotrypsin-like inhibition using PI-1833 analogs
  申请人：H. Lee Moffitt Cancer Center and Research Institute, Inc.

  公开号：US10662180B2

  公开（公告）日：2020-05-26

  Focused library synthesis and medicinal chemistry on an oxadiazole-isopropylamide core proteasome inhibitor provided the lead compound that strongly inhibits CT-L activity. Structure activity relationship studies indicate the amide moiety and two phenyl rings are sensitive toward synthetic modifications. Only para-substitution in the A-ring was important to maintain potent CT-L inhibitory activity. Hydrophobic residues in the A-ring's para-position and meta-pyridyl group at the B-ring significantly improved inhibition. The meta-pyridyl moiety improved cell permeability. The length of the aliphatic chain at the para position of the A-ring is critical with propyl yielding the most potent inhibitor, whereas shorter (i.e. ethyl, methyl or hydrogen) or longer (i.e. butyl, propyl and hexyl) chains demonstrating progressively less potency. Introduction of a stereogenic center next to the ether moiety (i.e. substitution of one of the hydrogens by methyl) demonstrated chiral discrimination in proteasome CT-L activity inhibition (the S-enantiomer was 35-40 fold more potent than the R-enantiomer).

  通过对一种噁二唑-异丙基酰胺核心蛋白酶体抑制剂进行重点文库合成和药物化学研究，获得了能强烈抑制 CT-L 活性的先导化合物。结构活性关系研究表明，酰胺分子和两个苯基环对合成修饰很敏感。只有 A 环中的对位取代对保持 CT-L 的强效抑制活性非常重要。A 环的对位疏水残基和 B 环的元吡啶基能显著改善抑制作用。偏吡啶基提高了细胞渗透性。A 环对位脂肪族链的长度至关重要，丙基产生的抑制作用最强，而较短的链（即乙基、甲基或氢基）或较长的链（即丁基、丙基和己基）的抑制作用则逐渐减弱。在醚分子旁边引入一个立体中心（即用甲基取代其中一个氢）可在蛋白酶体 CT-L 活性抑制方面显示出手性差异（S-对映体的效力比 R-对映体高 35-40 倍）。
• Cholesterol-Solubilizing Agents Related to the Gallstone Problem
  作者：C. Ainsworth、D. N. Benslay、J. Davenport、J. L. Hudson、D. Kau、T. M. Lin、R. R. Pfeiffer

  DOI：10.1021/jm00314a006

  日期：1967.3