(R)-2-hydroxy-4-phenylbutyric acid benzyl ester | 107832-06-4

• 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-hydroxy-4-phenylbutyric acid benzyl ester
• 英文别名: benzyl (S)-2-hydroxy-4-phenylbutanoate；benzyl (R)-2-hydroxy-4-phenylbutanoate；benzyl 2(R)-hydroxy-4-phenylbutyrate；benzyl (2R)-2-hydroxy-4-phenylbutanoate
• CAS: 107832-06-4
• 化学式: C₁₇H₁₈O₃
• 分子量: 270.328
• InChiKey: IVUUDHWOGKEQAN-MRXNPFEDSA-N

物化性质

• 沸点：
  426.9±33.0 °C(Predicted)
• 密度：
  1.156±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于二氯甲烷；乙酸乙酯

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 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：

  (R)-2-hydroxy-4-phenylbutyric acid benzyl ester 在 palladium on activated charcoal 吡啶 、 lithium hydroxide 、 氢气 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 生成 (R)-4-(4-Methoxy-benzenesulfonylamino)-2-[(S)-1-(morpholine-4-carbonyl)-3-phenyl-propylamino]-butyric acid
  参考文献：
  名称：

  Potent matrix metalloproteinase inhibitors: Amino-carboxylate compounds containing modifications of the P1 residue

  摘要：

  A series of amino-carboxylate inhibitors of matrix metalloproteinases containing different p1 modifications have been synthesized. It was discovered that a toluenesulfonamide-type substituent at the P1 position considerably enhances the binding affinity of inhibitors for stromelysin. Replacements of the P2'-P3' residues with nonpeptide components result in loss of inhibitory activity.

  DOI：

  10.1016/0960-894x(96)00028-5
• 作为产物：
  描述：

  (R)-2-羟基-4-苯基丁酸 、 溴甲苯 在 caesium carbonate 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 (R)-2-hydroxy-4-phenylbutyric acid benzyl ester
  参考文献：
  名称：

  Enniatin A Analogues as Novel Hsp90 Inhibitors that Modulate Triple-Negative Breast Cancer

  摘要：

  DOI：

  10.1021/acsmedchemlett.3c00423

文献信息

• METHOD FOR PRODUCING OPTICALLY ACTIVE 2-HYDROXY ESTER AND NOVEL INTERMEDIATE COMPOUND
  申请人：Shiina Isamu

  公开号：US20110319650A1

  公开（公告）日：2011-12-29

  Disclosed is a method for producing an optically active 2-hydroxy ester, comprising selectively esterifying one enantiomer of a racemic 2-hydroxy ester in a solvent containing a catalyst such as tetramisole or benzotetramisole, and a carboxylic acid anhydride, or a carboxylic acid anhydride and a carboxylic acid. In particular, in the case where the solvent contains a carboxylic acid anhydride, but does not contain a carboxylic acid, as the carboxylic acid anhydride, a carboxylic acid anhydride containing a tertiary or quaternary carbon atom in the a-position is used. On the other hand, in the case where the solvent contains a carboxylic acid anhydride and a carboxylic acid, as the carboxylic acid, a carboxylic acid containing a tertiary or quaternary carbon atom in the a-position is used.

  揭示了一种生产光学活性2-羟基酯的方法，包括在含有催化剂（如四氮唑或苯基四氮唑）和羧酸酐，或者羧酸酐和羧酸的溶剂中，选择性地酯化一个二羟基酯的对映体。特别是，在溶剂中含有羧酸酐但不含有羧酸的情况下，作为羧酸酐，使用含有三级或四级碳原子的α-位置的羧酸酐。另一方面，在溶剂中含有羧酸酐和羧酸的情况下，作为羧酸，使用含有三级或四级碳原子的α-位置的羧酸。
• Proline ester and preparation containing the same for percutaneous administration
  申请人：Furuishi Takayuki

  公开号：US20050288232A1

  公开（公告）日：2005-12-29

  A proline ester represented by the following formula (I): wherein R 1 represents a hydroxy-lower alkyl group, a lower alkoxy-lower alkyl group, or a lower alkoxy-lower alkoxy-lower alkyl group or a pharmaceutically acceptable salt thereof. The proline ester (I) of the present invention and a pharmaceutically acceptable salt thereof are useful as a prodrug of enalaprilat, which is a medicine useful for preventing or treating circulatory diseases such as hypertension, cardiac diseases (e.g., cardiac hypertrophy, cardiac failure, and myocardial infarct), nephritis, and apoplexy. Thus, a drug containing the ester or a salt thereof is preferably formulated to a percutaneous preparation, particularly a patch, from the viewpoint of medicinal activity and use.

  以下是翻译结果： 一种由以下式子(I)所表示的脯氨酸酯： 其中R1代表羟基-低烷基基团、低烷氧基-低烷基基团或低烷氧基-低烷氧基-低烷基基团，或其药学上可接受的盐。本发明的脯氨酸酯(I)及其药学上可接受的盐可作为依那普利酸的前药，该药物可用于预防或治疗循环系统疾病，如高血压、心脏疾病（如心肌肥大、心力衰竭和心肌梗死）、肾炎和中风。因此，含有该酯或其盐的药物最好从药效和用途的角度来看，制成经皮制剂，特别是贴片。
• PROLINE ESTER AND PREPARATION CONTAINING THE SAME FOR PERCUTANEOUS ADMINISTRATION
  申请人：Toaeiyo Ltd.

  公开号：EP1538158A1

  公开（公告）日：2005-06-08

  A proline ester represented by the following formula (I) : wherein R1 represents a hydroxy-lower alkyl group, a lower alkoxy-lower alkyl group, or a lower alkoxy-lower alkoxy-lower alkyl group or a pharmaceutically acceptable salt thereof. The proline ester (I) of the present invention and a pharmaceutically acceptable salt thereof are useful as a prodrug of enalaprilat, which is a medicine useful for preventing or treating circulatory diseases such as hypertension, cardiac diseases (e.g., cardiac hypertrophy, cardiac failure, and myocardial infarct), nephritis, and apoplexy. Thus, a drug containing the ester or a salt thereof is preferably formulated to a percutaneous preparation, particularly a patch, from the viewpoint of medicinal activity and use.

  由下式（I）代表的脯氨酸酯： 其中 R1 代表羟基-低级烷基、低级烷氧基-低级烷基或低级烷氧基-低级烷氧基-低级烷基或其药学上可接受的盐。 本发明的脯氨酸酯（I）及其药学上可接受的盐可用作依那普利拉的原药，而依那普利拉是一种可用于预防或治疗循环系统疾病的药物，如高血压、心脏病（如心脏肥大、心力衰竭和心肌梗塞）、肾炎和肾功能衰竭。因此，从药用活性和用途的角度来看，含有酯或其盐的药物最好配制成经皮制剂，特别是贴剂。
• A convenient method for the kinetic resolution of racemic 2-hydroxyalkanoates using diphenylacetic anhydride (DPHAA) and a chiral acyl-transfer catalyst
  作者：Kenya Nakata、Akihiro Sekiguchi、Isamu Shiina

  DOI：10.1016/j.tetasy.2011.08.018

  日期：2011.9

  Diphenylacetic anhydride (DPHAA) was found to be a useful reagent for the kinetic resolution of racemic 2-hydroxyalkanoates in the presence of a catalytic amount of (R)-benzotetramisole ((R)-BTM). The combined use of DPHAA and (R)-BTM effectively produced a variety of the optically active 2-hydroxyalkanoates and the corresponding 2-acyloxyalkanoates from racemic 2-hydroxyalkanoates (s-values = 42-177). A fairly broad substrate scope was demonstrated by this novel chiral induction system. We also revealed that the use of only 0.3 equiv of DPHAA is enough to provide the optically active 2-acyloxyalkanoates in good yields and with excellent ee's by the added use of 0.3 equiv of pivalic anhydride for the kinetic resolution of the racemic 2-hydroxyalkanoates. (C) 2011 Elsevier Ltd. All rights reserved.
• Structure-based design of dipeptide derivatives for the human neutral endopeptidase
  作者：Kensuke Misawa、Yasuto Suzuki、Satoshi Takahashi、Atsushi Yoshimori、Ryoko Takasawa、Yusuke Shibuya、Sei-ichi Tanuma

  DOI：10.1016/j.bmc.2011.08.064

  日期：2011.10

  Neutral endopeptidase (NEP) plays a key role in the metabolic inactivation of various bioactive peptides such as atrial natriuretic peptide (ANP), endothelins, and enkephalins. Furthermore, NEP is known to work as elastase in skin fibroblast. Therefore, effective inhibitors of NEP offer significant therapeutic interest as antihypertensives, analgesics, and skin anti-aging agents. Recently, the X-ray crystal structure of human NEP complexed with phosphoramidon has been reported and provided insights into the active site specificity of NEP. Here, we designed new inhibitors by using in silico molecular modeling and synthesized them by short steps. Expectedly, we found highly effective inhibitors with sub-nanomolar levels of IC(50) values. These results indicate that our structure-based molecular designing program is useful for obtaining novel NEP inhibitors. Furthermore, these inhibitors may be attractive leads for the generation of new pharmaceuticals for NEP-related diseases. (C) 2011 Elsevier Ltd. All rights reserved.