4-(benzyloxy)-2-isopropylbutanoic acid | 1161749-05-8

• 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: 4-(benzyloxy)-2-isopropylbutanoic acid
• 英文别名: 4-Benzyloxy-2-isopropylbutanoic acid；3-methyl-2-(2-phenylmethoxyethyl)butanoic acid
• CAS: 1161749-05-8
• 化学式: C₁₄H₂₀O₃
• 分子量: 236.311
• InChiKey: LEVMKWWAANYUHG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  17
• 可旋转键数：
  7
• 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：

  4-(benzyloxy)-2-isopropylbutanoic acid 在 吡啶 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成
  参考文献：
  名称：

  通过布朗斯台德酸催化动力学拆分轻松合成多功能对映体富集的α-取代的羟基酯

  摘要：

  描述了通过动力学拆分事件有效合成对映体富集的α-取代的γ-羟基酯的方法。在手性布朗斯台德酸的存在下，大块外消旋酯选择性地内酯化，得到可回收的对映体富集的羟基酯和内酯。这些酯是用途广泛的结构单元，可以很容易地转化为合成有用的材料。

  DOI：

  10.1021/ol400207t
• 作为产物：
  描述：

  2-benzyloxyethyl(isopropyl)malonic acid 反应 1.0h， 以2.64 g的产率得到4-(benzyloxy)-2-isopropylbutanoic acid
  参考文献：
  名称：

  Selective inhibitors of plasmepsin II of Plasmodium falciparum on the basis of pepstatin

  摘要：

  A number of new inhibitors of plasmepsin II (PlmII) Plasmodium falciparum, which was one of the key factors of survival of malarial parasite, was synthesized. The inhibitors were analogues of pepstatin with different substitutions for the alanine residue. Effects of the inhibitors on human PlmII and cathepsin D were studied. Inhibition of PlmII by the substrate was found. This discovery required modification of the Henderson method for determination of inhibition constants. Two synthesized inhibitors were shown to exhibit a pronounced selectivity to PlmII (K(i) = 5.5 and 5 nM) in comparison with that of cathepsin D (K(i) = 230 and 3000 nM, respectively).

  DOI：

  10.1134/s1068162008060034

文献信息

• Structure-based drug design of novel and highly potent pyruvate dehydrogenase kinase inhibitors
  作者：Yuki Bessho、Tatsuo Akaki、Yoshinori Hara、Maki Yamakawa、Shingo Obika、Genki Mori、Minoru Ubukata、Katsutaka Yasue、Yoshitomi Nakane、Yasuo Terasako、Takuya Orita、Satoki Doi、Tomoko Iwanaga、Ayumi Fujishima、Tsuyoshi Adachi、Hiroshi Ueno、Takahisa Motomura

  DOI：10.1016/j.bmc.2021.116514

  日期：2021.12

  explored, and the PDHK2 X-ray structure with a representative compound revealed a novel ATP lid conformation in which the phenyl ring of Phe326 mediated the interaction of the Arg258 sidechain and the compound. Compounds with amide linkers were designed to release the ATP lid by forming an intramolecular pi-pi interaction, and these compounds showed single-digit nM IC50 values in an enzymatic assay. We

  丙酮酸脱氢酶激酶 (PDHK) 是许多疾病（包括糖尿病和癌症）的迷人药物靶点。在本报告中，我们描述了我们基于结构的药物设计的三环先导化合物的结果，这导致在酶测定中发现了高效的 PDHK2 和 PDHK4 双重抑制剂。探索了三环核心的 C3 位，具有代表性化合物的 PDHK2 X 射线结构揭示了一种新的 ATP 盖构象，其中 Phe326 的苯环介导了 Arg258 侧链与化合物的相互作用。具有酰胺接头的化合物旨在通过形成分子内 pi-pi 相互作用来释放 ATP 盖，这些化合物显示单位数 nM IC 50酶测定中的值。我们还探索了三环核心的 C4 位以重现观察到的与 C3 位取代的相互作用，并且吡咯烷化合物显示出相同水平的 IC 50值。通过对接模拟优化与 Asn255 侧链的相互作用，具有 2-羧基吡咯部分的化合物也显示出个位数的 nM IC 50值，而与 Arg258 侧链没有阳离子-pi
• [EN] CYCLIC PHOSPHATE SUBSTITUTED NUCLEOSIDE DERIVATIVES AND METHODS OF USE THEREOF FOR THE TREATMENT OF VIRAL DISEASES<br/>[FR] DÉRIVÉS DE NUCLÉOSIDES CYCLIQUES À SUBSTITUTION PHOSPHATE ET LEURS PROCÉDÉS D'UTILISATION POUR LE TRAITEMENT DE MALADIES VIRALES
  申请人：MERCK SHARP & DOHME

  公开号：WO2017223020A1

  公开（公告）日：2017-12-28

  The present invention relates to Cyclic Phosphate Substituted Nucleoside Derivatives of Formula (I), and pharmaceutically acceptable salts thereof, wherein A, B, Q, V, R1, R2 and R3 are as defined herein. The present invention also relates to compositions comprising a Cyclic Phosphate Substituted Nucleoside Derivative, and methods of using the Cyclic Phosphate Substituted Nucleoside Derivatives for treating or preventing HCV infection in a patient.

  本发明涉及公式（I）的环磷酸酯取代核苷衍生物及其药用可接受的盐，其中A、B、Q、V、R1、R2和R3如本文所定义。本发明还涉及包含环磷酸酯取代核苷衍生物的组合物，以及使用这些环磷酸酯取代核苷衍生物治疗或预防患者HCV感染的方法。
• CYCLIC PHOSPHATE SUBSTITUTED NUCLEOSIDE DERIVATIVES AND METHODS OF USE THEREOF FOR THE TREATMENT OF VIRAL DISEASES
  申请人：BOGEN STEPHANE

  公开号：US20200179428A1

  公开（公告）日：2020-06-11

  The present invention relates to Cyclic Phosphate Substituted Nucleoside Derivatives of Formula (I), and pharmaceutically acceptable salts thereof, wherein A, B, Q, V, R 1 , R 2 and R 3 are as defined herein. The present invention also relates to compositions comprising a Cyclic Phosphate Substituted Nucleoside Derivative, and methods of using the Cyclic Phosphate Substituted Nucleoside Derivatives for treating or preventing HCV infection in a patient.
• Facile Synthesis of Versatile Enantioenriched α-Substituted Hydroxy Esters through a Brønsted Acid Catalyzed Kinetic Resolution
  作者：Ghassan Qabaja、Jennifer E. Wilent、Amanda R. Benavides、George E. Bullard、Kimberly S. Petersen

  DOI：10.1021/ol400207t

  日期：2013.3.15

  An efficient synthesis of enantioenriched α-substituted γ-hydroxy esters via a kinetic resolution event is described. Bulky racemic esters in the presence of a chiral Brønsted acid selectively lactonize to yield a recoverable enantioenriched hydroxy ester and lactone. These esters are highly versatile building blocks that can readily be converted to synthetically useful materials.

  描述了通过动力学拆分事件有效合成对映体富集的α-取代的γ-羟基酯的方法。在手性布朗斯台德酸的存在下，大块外消旋酯选择性地内酯化，得到可回收的对映体富集的羟基酯和内酯。这些酯是用途广泛的结构单元，可以很容易地转化为合成有用的材料。
• Selective inhibitors of plasmepsin II of Plasmodium falciparum on the basis of pepstatin
  作者：L. D. Rumsh、A. G. Mikhailova、I. V. Mikhura、I. A. Prudchenko、L. D. Chikin、I. I. Mikhaleva、E. N. Kaliberda、N. I. Dergousova、E. E. Mel’nikov、A. A. Formanovskii

  DOI：10.1134/s1068162008060034

  日期：2008.11

  A number of new inhibitors of plasmepsin II (PlmII) Plasmodium falciparum, which was one of the key factors of survival of malarial parasite, was synthesized. The inhibitors were analogues of pepstatin with different substitutions for the alanine residue. Effects of the inhibitors on human PlmII and cathepsin D were studied. Inhibition of PlmII by the substrate was found. This discovery required modification of the Henderson method for determination of inhibition constants. Two synthesized inhibitors were shown to exhibit a pronounced selectivity to PlmII (K(i) = 5.5 and 5 nM) in comparison with that of cathepsin D (K(i) = 230 and 3000 nM, respectively).