Tert-butyl-dimethyl-(1-pyridin-2-ylsulfanyloct-1-enoxy)silane | 914939-72-3

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: Tert-butyl-dimethyl-(1-pyridin-2-ylsulfanyloct-1-enoxy)silane
• CAS: 914939-72-3
• 化学式: C₁₉H₃₃NOSSi
• 分子量: 351.629
• InChiKey: LWUMJXCPDDTBPT-UHFFFAOYSA-N

物化性质

• 沸点：
  410.6±41.0 °C(Predicted)
• 密度：
  0.97±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.01
• 重原子数：
  23
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  47.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  Tert-butyl-dimethyl-(1-pyridin-2-ylsulfanyloct-1-enoxy)silane 、 (S)-3-<(tert-butyldimethylsilyl)oxy>-4-(tosyloxy)butanal 在 zinc(II) chloride 、 氢氟酸 作用下， 以 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 60.0h， 以12 mg的产率得到(S)-3-((2S,3S)-3-hexyl-4-oxooxetan-2-yl)-2-hydroxypropyl 4-methylbenzenesulfonate
  参考文献：
  名称：

  Synthesis of Novel β-Lactone Inhibitors of Fatty Acid Synthase

  摘要：

  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.

  DOI：

  10.1021/jm800321h
• 作为产物：
  描述：

  S-(pyridin-2-yl)octanethioate 、 叔丁基二甲基氯硅烷 在 lithium hexamethyldisilazane 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 Tert-butyl-dimethyl-(1-pyridin-2-ylsulfanyloct-1-enoxy)silane
  参考文献：
  名称：

  Synthesis of Novel β-Lactone Inhibitors of Fatty Acid Synthase

  摘要：

  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.

  DOI：

  10.1021/jm800321h

文献信息

• [EN] COMPOUNDS FOR THE REDUCING LIPOTOXIC DAMAGE<br/>[FR] COMPOSÉS POUR LA RÉDUCTION DE LÉSIONS LIPOTOXIQUES
  申请人：MAYO FOUND MEDICAL EDUCATION & RES

  公开号：WO2019014434A1

  公开（公告）日：2019-01-17

  Provided herein are novel lipase inhibitors and methods for using the same to treat inflammation, multisystem organ failure, necrotic pancreatic acinar cell death, acute pancreatitis, sepsis (e.g., culture negative sepsis), burns, and acne. For example, provided herein are two novel lipase inhibitors useful in the methods described herein: (I) (II) or a pharmaceutically acceptable salt thereof.

  本文提供了新型脂肪酶抑制剂以及使用这些抑制剂治疗炎症、多系统器官衰竭、坏死性胰腺腺泡细胞死亡、急性胰腺炎、败血症（如无菌性败血症）、烧伤和痤疮的方法。例如，本文提供了两种在本文描述的方法中有用的新型脂肪酶抑制剂：（I）（II）或其药用可接受的盐。
• Chemical Modification and Organelle-Specific Localization of Orlistat-Like Natural-Product-Based Probes
  作者：Peng-Yu Yang、Kai Liu、Chongjing Zhang、Grace Y. J. Chen、Yuan Shen、Mun Hong Ngai、Martin J. Lear、Shao Q. Yao

  DOI：10.1002/asia.201100306

  日期：2011.10.4

  Orlistat, also known as tetrahydrolipstatin (THL), is an FDA‐approved anti‐obesity drug with potential anti‐cancer activity. Previously, we developed a chemical proteomic approach, based on the Orlistat‐like probe (1a) for large‐scale identification of unknown cellular targets of Orlistat in human hepatocytes. In this article, we report the chemical synthesis and biological evaluation of an expanded

  奥利司他（Orlistat），也称为四氢脂质他汀（THL），是FDA批准的抗肥胖药，具有潜在的抗癌活性。以前，我们基于类Orlistat探针（1a）用于大规模鉴定人肝细胞中奥利司他的未知细胞靶标。在本文中，我们报告了一系列扩展的Orlistat样化合物的化学合成和生物学评估，目的是进一步剖析和操纵Orlistat的潜在细胞靶标。为此，我们对活HepG2细胞中的这些化合物进行了基于蛋白质组的活动分析和大规模下拉/ LCMS分析，并成功地确定了Orlistat及其结构类似物的许多推定细胞靶标。通过定性评估针对17种奥利司他类似物的潜在蛋白质命中的光谱计数，我们获得了这些探针的共同和独特靶标。我们的结果表明，奥利司他的微妙结构修饰导致该药物的细胞效能和靶标分布均发生了显着变化。为了进一步提高Orlistat的细胞活性，我们成功地将成熟的AGT / SNAP标签技术应用于我们的细胞渗透性含苄基鸟嘌
• 一种奥利司他关键中间体的精制方法
  申请人：植恩生物技术股份有限公司

  公开号：CN112625009A

  公开（公告）日：2021-04-09

  本发明公开了一种奥利司他关键中间体精制方法及其关键中间体杂质和制备方法。所述精制方法为化合物I在有机溶剂或混合有机溶剂中重结晶除去工艺中难以除去的杂质1～杂质5，该方法对杂质1～杂质5的选择性好，该方法操作简便、成本低、适合工业化生产。本发明还提供了杂质3及其制备方法和作为奥利司他关键中间体(3S,4S)‑3‑己基‑4‑〔(R)‑2‑(羟基十三烷基)〕氧杂环丁‑2‑酮(化合物I)的杂质对照品中的应用。