α-Oxo-ε-phenyl-capronsaeure | 79023-13-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 英文名称: α-Oxo-ε-phenyl-capronsaeure
• 英文别名: 2-Oxo-6-phenylcaproic acid；2-oxo-6-phenylhexanoic acid
• CAS: 79023-13-5
• 化学式: C₁₂H₁₄O₃
• 分子量: 206.241
• InChiKey: KODALSDOOPIEJT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  15
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  α-Oxo-ε-phenyl-capronsaeure 、 2-苯乙胺 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以71%的产率得到2-oxo-N-phenethyl-6-phenylhexanamide
  参考文献：
  名称：

  Structure–Activity Relationship Studies of α-Ketoamides as Inhibitors of the Phospholipase A and Acyltransferase Enzyme Family

  摘要：

  The phospholipase A and acyltransferase (PLAAT) family of cysteine hydrolases consists of five members, which are involved in the Ca2+-independent production of N-acylphosphatidylethanolamines (NAPEs). NAPEs are lipid precursors for bioactive N-acylethanolamines (NAEs) that are involved in various physiological processes such as food intake, pain, inflammation, stress, and anxiety. Recently, we identified alpha-ketoamides as the first pan-active PLAAT inhibitor scaffold that reduced arachidonic acid levels in PLAAT3-overexpressing U2OS cells and in HepG2 cells. Here, we report the structure-activity relationships of the alpha-ketoamide series using activity-based protein profiling. This led to the identification of LEI-301, a nanomolar potent inhibitor for the PLAAT family members. LEI-301 reduced the NAE levels, including anandamide, in cells overexpressing PLAAT2 or PLAAT5. Collectively, LEI-301 may help to dissect the physiological role of the PLAATs.

  DOI：

  10.1021/acs.jmedchem.0c00522
• 作为产物：
  描述：

  4-苯基-1-丁基溴 在 碘 、 magnesium 、 三氟乙酸 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 α-Oxo-ε-phenyl-capronsaeure
  参考文献：
  名称：

  Structure–Activity Relationship Studies of α-Ketoamides as Inhibitors of the Phospholipase A and Acyltransferase Enzyme Family

  摘要：

  The phospholipase A and acyltransferase (PLAAT) family of cysteine hydrolases consists of five members, which are involved in the Ca2+-independent production of N-acylphosphatidylethanolamines (NAPEs). NAPEs are lipid precursors for bioactive N-acylethanolamines (NAEs) that are involved in various physiological processes such as food intake, pain, inflammation, stress, and anxiety. Recently, we identified alpha-ketoamides as the first pan-active PLAAT inhibitor scaffold that reduced arachidonic acid levels in PLAAT3-overexpressing U2OS cells and in HepG2 cells. Here, we report the structure-activity relationships of the alpha-ketoamide series using activity-based protein profiling. This led to the identification of LEI-301, a nanomolar potent inhibitor for the PLAAT family members. LEI-301 reduced the NAE levels, including anandamide, in cells overexpressing PLAAT2 or PLAAT5. Collectively, LEI-301 may help to dissect the physiological role of the PLAATs.

  DOI：

  10.1021/acs.jmedchem.0c00522

文献信息

• Substituted oxocarboxylic acids, processes for their preparation, their
  申请人：Byk Gulden Lomberg Chemische Fabrik Gesellschaft

  公开号：US04334089A1

  公开（公告）日：1982-06-08

  Substituted oxocarboxylic acids of the formula I ##STR1## wherein R.sup.1 denotes a hydrogen atom, a halogen atom, a hydroxyl group, a lower alkyl group, a lower alkoxy group or a trifluoromethyl group, R.sup.2 denotes a hydrogen atom or a halogen atom and n denotes an integer from 3 to 8, and their salts display a hypoglycaemic action in warm-blooded animals. Processes for the preparation of the new compounds and of the intermediate products required for their preparation, as well as of the corresponding medicaments are described.

  公式I中的替代羰基酸： ##STR1## 其中R.sup.1表示氢原子、卤素原子、羟基、低碳基、低氧基或三氟甲基基团，R.sup.2表示氢原子或卤素原子，n表示3到8的整数，它们的盐在恒温动物中显示出降血糖作用。本文描述了制备新化合物及其制备所需中间体和相应药物的过程。
• Substituierte Oxocarbonsäuren, Verfahren zu ihrer Herstellung, ihre Verwendung und sie enthaltende Arzneimittel
  申请人：Byk Gulden Lomberg Chemische Fabrik GmbH

  公开号：EP0051077A1

  公开（公告）日：1982-05-12

  Substituierte Oxocarbonsäuren der Formel worin R' ein Wasserstoffatom, ein Halogenatom, eine Hydroxygruppe, eine Niederalkylgruppe, eine Niederalkoxygruppe oder eine Trifluormethylgruppe, R2 ein Wasserstoffatom oder ein Halogenatom und n eine ganze Zahl von 3 bis 8 bedeuten, und ihre Salze entfalten an Warmblütlern eine hypoglykämische Wirkung. Verfahren zur Herstellung der neuen Verbindungen und der zu ihrer Herstellung benötigten Zwischenprodukte sowie der entsprechenden Arzneimittel werden beschrieben.

  式中的取代的氧羧酸 其中 R'为氢原子、卤素原子、羟基、低级烷基、低级烷氧基或三氟甲基，R2 为氢原子或卤素原子，n 为 3 至 8 的整数，它们的盐对温血动物具有降血糖作用。本文介绍了新化合物的制备过程、制备这些化合物所需的中间体以及相应的药物。
• Method of treating cancer
  申请人：Intensity Therapeutics, Inc.

  公开号：US10888618B2

  公开（公告）日：2021-01-12

  The invention provides a method for treating cancer using a coadministration strategy that combines local codelivery of a therapeutic agent and an intracellular penetration enhancing agent, and optionally in further combination with local administration of an immunotherapeutic agent, such as a cancer vaccine or NKT agonist. The invention also provides a method for treating cancer using an intracellular penetration enhancing agent. The methods of the invention aim to substantially kill and/or destroy the target tumor cells, as well as those cancerous cells that have metastasized to other parts of the body.

  本发明提供了一种使用联合给药策略治疗癌症的方法，该策略结合了治疗剂和细胞内渗透增强剂的局部联合给药，并可选择进一步结合免疫治疗剂（如癌症疫苗或 NKT 激动剂）的局部给药。本发明还提供了一种使用细胞内渗透增强剂治疗癌症的方法。本发明的方法旨在杀死和/或消灭目标肿瘤细胞以及转移到身体其他部位的癌细胞。
• SUBSTITUIERTE OXOCARBONSÄUREN, VERFAHREN ZU IHRER HERSTELLUNG, IHRE VERWENDUNG UND SIE ENTHALTENDE ARZNEIMITTEL
  申请人：Byk Gulden Lomberg Chemische Fabrik GmbH

  公开号：EP0038343B1

  公开（公告）日：1984-12-27
• OXIDOREDUKTASE AUS METSCHNIKOWIA ZOBELLII
  申请人：IEP GmbH

  公开号：EP1685248B1

  公开（公告）日：2010-06-09