S-(pyridin-2-yl)octanethioate | 89397-99-9

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: S-(pyridin-2-yl)octanethioate
• 英文别名: S-pyridin-2-yl octanethioate；S-2-Pyridylthiocaprylate；octanethioic acid S-pyridin-2-yl-ester；thiooctanoic acid-S-pyridin-2-yl ester
• CAS: 89397-99-9
• 化学式: C₁₃H₁₉NOS
• 分子量: 237.366
• InChiKey: JRVYPYKANCYOFX-UHFFFAOYSA-N

物化性质

• 沸点：
  350.6±15.0 °C(Predicted)
• 密度：
  1.05±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  16
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  55.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  S-(pyridin-2-yl)octanethioate 在 三乙胺 、 N,N-二甲基甲酰胺 、 zinc(II) chloride 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 3.17h， 生成
  参考文献：
  名称：

  A strategy for dual inhibition of the proteasome and fatty acid synthase with belactosin C-orlistat hybrids

  摘要：

  The proteasome, a validated cellular target for cancer, is central for maintaining cellular homeostasis, while fatty acid synthase (FAS), a novel target for numerous cancers, is responsible for palmitic acid biosynthesis. Perturbation of either enzymatic machine results in decreased proliferation and ultimately cellular apoptosis. Based on structural similarities, we hypothesized that hybrid molecules of belactosin C, a known proteasome inhibitor, and orlistat, a known inhibitor of the thioesterase domain of FAS, could inhibit both enzymes. Herein, we describe proof-of-principle studies leading to the design, synthesis and enzymatic activity of several novel, B-lactone-based, dual inhibitors of these two enzymes. Validation of dual enzyme targeting through activity-based proteome profiling with an alkyne probe modeled after the most potent inhibitor, and preliminary serum stability studies of selected derivatives are also described. These results provide proof of concept for dual targeting of the proteasome and fatty acid synthase-thioesterase (FAS-TE) enabling a new approach for the development of drug-candidates with potential to overcome resistance. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.01.020
• 作为产物：
  描述：

  2-巯基吡啶 、 辛酰氯 在 TEA 作用下， 以 二氯甲烷 为溶剂， 生成 S-(pyridin-2-yl)octanethioate
  参考文献：
  名称：

  2-吡啶基硫酯的甲硅烷基乙烯酮缩醛与苯甲醛的非对映选择性醛醇缩合

  摘要：

  由2-吡啶基硫酯衍生的（E）-O-甲硅烷基烯酮-O，S-缩醛与苯甲醛的TiCl 4介导的醇醛缩合反应仅得到顺式-醛醇缩合产物。相反，BF 3介导的反应提供了相应的反异构体作为主要产物。假定螯合和无环过渡态是为了解释观察到的选择性。

  DOI：

  10.1016/0040-4039(95)01231-6

文献信息

• [DE] ALKYLCARBAMAT-SUBSTITUIERTE BUTYROLACTONE ALS LIPASE-INHIBITOREN<br/>[EN] ALKYL CARBAMATE-SUBSTITUTED BUTYROLACTONES SERVING AS LIPASE INHIBITORS<br/>[FR] BUTYROLACTONES SUBSTITUEES PAR CARBAMATE D'ALKYLE, UTILISEES COMME INHIBITEURS DE LIPASE
  申请人：SOLVAY PHARM GMBH

  公开号：WO2005080366A1

  公开（公告）日：2005-09-01

  Es werden substituierte β-Lactone (Oxetanone) der allgemeinen Formel (I), worin R1, R2 und n die in der Beschreibung angegebenen Bedeutungen besitzen sowie diese Verbindungen enthaltende Arzneimittel mit die Pankreaslipase hemmender Wirkung beschrieben. Ferner werden ein Verfahren zur Herstellung der Verbindungen der Formel (I) und Zwischenprodukte dieses Verfahrens angegeben.

  这里描述了取代的β-内酰胺（Oxetanone）的一般公式（I），其中R1、R2和n是在描述中指定的含义，以及包含这些化合物的药物，具有抑制胰腺脂肪酶的作用。此外，还提供了一种制备公式（I）的化合物和该方法的中间产物的方法。
• Alkyl carbamate-substituted beta-lactones, process and intermediate products for their preparation, and pharmaceutical compositions containing them
  申请人：Antel Jochen

  公开号：US20050197386A1

  公开（公告）日：2005-09-08

  Substituted β-lactones (oxetanones) corresponding to the formula I, wherein R 1 , R 2 and n have the meanings given in the specification, and pharmaceutical compositions which contain these compounds and have a pancreatic lipase-inhibiting action, as well as a process for the preparation of the compounds of Formula I and intermediate products of this process.

  取代的β-内酰胺（氧杂环丙烷酮）对应于公式I， 其中R1，R2和n具有说明书中给出的含义，以及包含这些化合物的药物组合物，并具有胰腺脂肪酶抑制作用，以及用于制备公式I化合物和此过程中间体的方法。
• PREPARATION METHOD OF (3S,4S)-3-HEXYL-4-((R)-2-HYDROXYTRIDECYL)-OXETAN-2-0NE AND THE PRODUCT OF THAT METHOD
  申请人：Qin Yong

  公开号：US20110046400A1

  公开（公告）日：2011-02-24

  The present invention relates to a method for the preparation of (3S,4S)-3-hexyl-4-((R)-2-hydroxytridecyl)-oxetan-2-one and a product of the method. The method includes the following steps: a) reducing a substance represented by formula (II) to obtain a substance represented by formula (III), and then oxidizing the substance represented by formula (III) to form a substance represented by formula (IV); b) acylating n-octanoic acid to obtain n-octanoyl chloride using thionyl dichloride, then condensing the obtained n-octanoyl chloride with 2-mercapto-pyridine under basic condition to form a substance represented by formula (V), and then converting the substance represented by formula (V) to a substance represented by formula (VI); c) reacting the substance obtained in the step a) with the substance obtained in the step b) under catalytic condition of Lewis acid to generate a substance represented by formula (VII), and then reacting with a Lewis acid. The meanings of the signs in these formulas are the same as those in the description.

  本发明涉及一种制备(3S,4S)-3-己基-4-[(R)-2-羟基十三烷基]-氧杂环戊烷-2-酮及其制备方法的产品。该方法包括以下步骤：a) 还原式（II）所表示的物质以获得式（III）所表示的物质，然后氧化式（III）所表示的物质以形成式（IV）所表示的物质；b) 用氯化硫酰将正辛酸酰化为正辛酰氯，然后在碱性条件下将所得的正辛酰氯与2-巯基吡啶缩合以形成式（V）所表示的物质，然后将式（V）所表示的物质转化为式（VI）所表示的物质；c) 在Lewis酸的催化条件下将步骤a)中获得的物质与步骤b)中获得的物质反应以生成式（VII）所表示的物质，然后与Lewis酸反应。这些公式中符号的含义与说明中的相同。
• Activity-Based Proteome Profiling of Potential Cellular Targets of Orlistat − An FDA-Approved Drug with Anti-Tumor Activities
  作者：Peng-Yu Yang、Kai Liu、Mun Hong Ngai、Martin J. Lear、Markus R. Wenk、Shao Q. Yao

  DOI：10.1021/ja907716f

  日期：2010.1.20

  Orlistat, or tetrahydrolipstatin (THL), is an FDA-approved antiobesity drug with potential antitumor activities. Cellular off-targets and potential side effects of Orlistat in cancer therapies, however, have not been extensively explored thus far. In this study, we report the total of synthesis of THL-like protein-reactive probes, in which extremely conservative modifications (i.e., an alkyne handle) were introduced in the parental THL structure to maintain the native biological properties of Orlistat, while providing the necessary functionality for target identification via the bio-orthogonal click chemistry. With these natural productlike, cell-permeable probes, we were able to demonstrate, for the first time, this chemical proteomic approach is suitable for the identification of previously unknown cellular targets of Orlistat. In addition to the expected fatty acid synthase (FAS), we identified a total of eight new targets, some of which were further validated by experiments including Western blotting, recombinant protein expression, and site-directed mutagenesis. Our findings have important implications in the consideration of Orlistat as a potential anticancer drug at its early stages of development for cancer therapy. Our strategy should be broadly useful for off-target identification against quite a number of existing drugs and/or candidates, which are also covalent modifiers of their biological targets.
• Synthesis of Novel β-Lactone Inhibitors of Fatty Acid Synthase
  作者：Robyn D. Richardson、Gil Ma、Yatsandra Oyola、Manuel Zancanella、Lynn M. Knowles、Piotr Cieplak、Daniel Romo、Jeffrey W. Smith

  DOI：10.1021/jm800321h

  日期：2008.9.11

  Fatty acid synthase (FAS) is necessary for growth and survival of tumor cells and is a promising drug target for oncology. Here, we report oil the syntheses and activity of novel inhibitors of the thioesterase domain of FAS. Using the structure of orlistat as a starting point, which contains a beta-lactone as the central pharmacophore, 28 novel congeners were synthesized and examined. Structural features such as the length of the alpha- and beta-alkyl chains, their chemical composition, and arnino ester substitutions were altered and tile resulting compounds explored for inhibitory activity toward the thioesterase domain of FAS. Nineteen congeners show improved potency for FAS in biochemical assays relative to orlistat. Three of that subset, including the natural product valilactone, also display all increased potency in inducing tumor cell death and improved solubility compared to orlistat. These findings Support the idea that all orlistat congener can be optimized for use in a preclinical drug design and for clinical drug development.