2-benzyl-3-hydroxy-pent-4-enethioic acid S-benzyl ester | 479495-61-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 2-benzyl-3-hydroxy-pent-4-enethioic acid S-benzyl ester
• 英文别名: (3S,2R)-2-benzyl-3-hydroxypent-4-enethioic acid S-benzyl ester；S-benzyl (2R,3S)-2-benzyl-3-hydroxypent-4-enethioate
• CAS: 479495-61-9
• 化学式: C₁₉H₂₀O₂S
• 分子量: 312.433
• InChiKey: CHAYLMGTGIOYLN-MSOLQXFVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  62.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-benzyl-3-hydroxy-pent-4-enethioic acid S-benzyl ester 在 哌啶 、 rink amide AM resin 吡啶 、 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 lithium hydroxide 、 氢氟酸 、 双氧水 、 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 4.83h， 生成 (Z)-8-amino-2-benzyl-3,7-dihydroxy-9-(4-hydroxy-phenyl)-non-4-enoic acid (1-carbamoyl-2-phenyl-ethyl)-amide
  参考文献：
  名称：

  High-Affinity Mu Opioid Receptor Ligands Discovered by the Screening of an Exhaustively Stereodiversified Library of 1,5-Enediols

  摘要：

  In this communication, we report the synthesis of an exhaustively stereodiversified library of 16 1,5-enediols (2) and the screening of these compounds for mu opioid receptor (MOR) binding. The stereochemical configuration of 2 strongly impacted the binding affinity, and (S,S,S,R)-2 exhibited a Ki of 8.8 nM for MOR, comparable to that of endomorphin-2 (Ki = 1.2 nM). Moreover, compounds 2 exhibited 5-86-fold selectivity for MOR over delta opioid receptor (DOR) and 16-150-fold selectivity for MOR over kappa opioid receptor (KOR). Additionally, analogues of 2 were synthesized which showed the importance of the trans olefin for receptor binding but that modifications of the C-terminal amino acid were well tolerated. Ligand 11 is noteworthy because it retains only one of the amide bonds present in 1, but binds MOR with an affinity of 10 nM and 110- and 600-fold selectivity for MOR over DOR and KOR. These results demonstrate the utility of stereochemical diversity in the discovery of bioactive small molecules.

  DOI：

  10.1021/ja027150p
• 作为产物：
  描述：

  、 苄硫醇 、 丙烯醛 在 三氟甲磺酸二丁硼 、 三乙胺 、 正丁基锂 、 三甲基铝 作用下， 以 二氯甲烷 、 四氢呋喃 为溶剂， 以79%的产率得到2-benzyl-3-hydroxy-pent-4-enethioic acid S-benzyl ester
  参考文献：
  名称：

  [EN] MU OPIOID RECEPTOR LIGANDS: METHODS OF USE AND SYNTHESIS
  [FR] LIGANDS DE RECEPTEUR OPIOIDE MU: PROCEDES D'UTILISATION ET DE SYNTHESE

  摘要：

  本文描述了从芳基取代的8-氨基-3,7-或3,6-二羟基烯酸或烷酸衍生的肽类模拟化合物，以及包括这些化合物的组合物，以及使用和制备这些化合物的方法。这些化合物在治疗应用中很有用，包括调节受试者（例如，哺乳动物、人类、狗、猫、马）的疾病症状。这些化合物通过它们与μ阿片受体（MOR）的结合亲和力在调节MOR方面很有用。

  公开号：

  WO2004033414A1

文献信息

• Mu opioid receptor ligands: methods of use and synthesis
  申请人：Harrison Bryce A.

  公开号：US20090093534A1

  公开（公告）日：2009-04-09

  Novel compounds and compositions including those compounds, as well as methods of using and making the compounds are herein described. The compounds are useful in therapeutic applications, including modulation of disease or disease symptoms in a subject (e.g., mammal, human, dog, cat, horse). The compounds are useful as modulators of the mu opioid receptor (MOR) through their binding affinity with that receptor.

  本文描述了包括这些化合物在内的新型化合物和组合物，以及使用和制造这些化合物的方法。这些化合物在治疗应用中有用，包括调节受试者（例如哺乳动物、人类、狗、猫、马）的疾病或疾病症状。这些化合物通过它们与μ阿片受体（MOR）的结合亲和力作为MOR的调节剂是有用的。
• Unpredictable Stereochemical Preferences for Mu Opioid Receptor Activity in an Exhaustively Stereodiversified Library of 1,4-Enediols
  作者：Zhangjie Shi、Bryce A. Harrison、Gregory L. Verdine

  DOI：10.1021/ol027237f

  日期：2003.3.1

  [GRAPHICS]Using olefin cross-metathesis, we synthesized a novel stereodiversified library of compounds 3 containing a trans-1,4-enediol. Screening this library for mu opioid receptor (MOR) affinity identified multiple high-affinity ligands and revealed that the stereochemical configuration varied widely among those ligands having the highest affinity. It was not possible to predict the configurations of the most active compounds 3 on the basis of the configuration of endomorphin-2, a known MOR peptide ligand, validating the diversity-based approach to ligand discovery.
• 2,6-Dimethyltyrosine Analogues of a Stereodiversified Ligand Library:  Highly Potent, Selective, Non-Peptidic μ Opioid Receptor Agonists
  作者：Bryce A. Harrison、Gavril W. Pasternak、Gregory L. Verdine

  DOI：10.1021/jm025608s

  日期：2003.2.1

  We recently reported the use of an exhaustively stereodiversified library based on endomorphin-2 (1) to discovery opioid receptor (MOR) ligands of type 2-4. Here, we report the synthesis and evaluation of 2,6-dimethyltyrosine analogues 5-10. These analogues showed improved affinity for MOR relative to 2-4. In the cases of 5 and 6, we synthesized and evaluated five stereoisomers of each, thereby discovering stereoisomers with unexpected potency, selectivity, and efficacy. These results illustrate the utility of acyclic, stereodiverse libraries.
• US7223888B2
  申请人：——

  公开号：US7223888B2

  公开（公告）日：2007-05-29
• US7759514B2
  申请人：——

  公开号：US7759514B2

  公开（公告）日：2010-07-20