(R)-2-(4-propyl-phenoxy)-propanoic acid

• 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: (R)-2-(4-propyl-phenoxy)-propanoic acid
• 英文别名: (2R)-2-(4-propylphenoxy)propanoic acid
• 化学式: C₁₂H₁₆O₃
• 分子量: 208.257
• InChiKey: BCGAQLXZWYPDCJ-SECBINFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

上下游信息

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	(R)-2-(4-propylphenoxy)propanoyl chloride	1401223-81-1	C12H15ClO2	226.703

反应信息

• 作为反应物：
  描述：

  (4-甲基苯氧基)乙酰氯 、 (R)-2-(4-propyl-phenoxy)-propanoic acid 、 氯化亚砜 以 苯 为溶剂， 以SO3-107 15f was isolated as yellow liquid (311 mg, 95%)的产率得到(R)-2-(4-propylphenoxy)propanoyl chloride
  参考文献：
  名称：

  PROTEASOME CHYMOTRYPSIN-LIKE INHIBITION USING PI-1833 ANALOGS

  摘要：

  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）。

  公开号：

  US20140073650A1
• 作为产物：
  描述：

  butyl 2-(4-n-propylphenoxy)propanoate 在 Candida rugosa lipase MY 、 sodium dodecyl-sulfate 作用下， 以 水 为溶剂， 反应 0.33h， 生成 (R)-2-(4-propyl-phenoxy)-propanoic acid
  参考文献：
  名称：

  A method to greatly improve the enantioselectivity of lipase-catalyzed hydrolysis using sodium dodecyl sulfate (SDS) as an additive

  摘要：

  The addition of sodium dodecyl sulfate (SDS) resulted in a dramatic improvement of the enantioselectivity of the lipasecatalyzed hydrolysis of racemic butyl 2-(4-substituted phenoxy)propanoates, racemic butyl 2-(4-isobutylphenyl)propanoate, and racemic butyl 2-(6-methoxy-2-naphthyl)propanoate in an aqueous buffer solution. An increase in the E value by up to two orders of magnitude was observed for some esters. As to the effects of SDS on the structure of a lipase, FT-IR and fluorescence measurements suggest some conformational change and/or an increase of the flexibility of the lipase, although the native secondary structure of the lipase is held even in the presence of 100 mM SDS. The origin of the enantioselectivity enhancement brought about by the addition of SDS is briefly discussed on the basis of the values of the initial rates obtained for each enantiomer of the substrate. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2005.10.003

文献信息

• 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）。
• [EN] PROTEASOME CHYMOTRYPSIN-LIKE INHIBITION USING PI-1833 ANALOGS<br/>[FR] INHIBITION DE CHYMOTRYPSINE-LIKE DU PROTÉASOME À L'AIDE D'ANALOGUES DE PI-1833
  申请人：H LEE MOFFITT CANCER CT & RES

  公开号：WO2012129564A3

  公开（公告）日：2012-12-27
• US9878999B2
  申请人：——

  公开号：US9878999B2

  公开（公告）日：2018-01-30
• A method to greatly improve the enantioselectivity of lipase-catalyzed hydrolysis using sodium dodecyl sulfate (SDS) as an additive
  作者：Shuichi Mori、Hiromi Yumoto、Rina Matsumi、Tomohiro Nishigaki、Yasuhito Ebara、Shin-ichi Ueji

  DOI：10.1016/j.tetasy.2005.10.003

  日期：2005.11

  The addition of sodium dodecyl sulfate (SDS) resulted in a dramatic improvement of the enantioselectivity of the lipasecatalyzed hydrolysis of racemic butyl 2-(4-substituted phenoxy)propanoates, racemic butyl 2-(4-isobutylphenyl)propanoate, and racemic butyl 2-(6-methoxy-2-naphthyl)propanoate in an aqueous buffer solution. An increase in the E value by up to two orders of magnitude was observed for some esters. As to the effects of SDS on the structure of a lipase, FT-IR and fluorescence measurements suggest some conformational change and/or an increase of the flexibility of the lipase, although the native secondary structure of the lipase is held even in the presence of 100 mM SDS. The origin of the enantioselectivity enhancement brought about by the addition of SDS is briefly discussed on the basis of the values of the initial rates obtained for each enantiomer of the substrate. (c) 2005 Elsevier Ltd. All rights reserved.
• 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）。