(S)-2-(1-(5-(环己基氨基甲酰基)-6-(丙硫基)吡啶-2-基)哌啶-3-基)乙酸 | 1024033-43-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: (S)-2-(1-(5-(环己基氨基甲酰基)-6-(丙硫基)吡啶-2-基)哌啶-3-基)乙酸
• 中文别名: (S)-2-(1-(5-(环己基氨基)羰基)-6-(丙硫基)吡啶-2-基)哌啶-3-基)乙酸
• 英文名称: 2-[(3S)-1-[5-(cyclohexylcarbamoyl)-6-propylsulfanylpyridin-2-yl]piperidin-3-yl]acetic acid
• 英文别名: 2-[(3S)-1-[5-(cyclohexylcarbamoyl)-6-propylsulfanylpyridin-2-yl]-3-piperidyl]acetic acid；(S)-2-(1-(5-(cyclohexylcarbamoyl)-6-(propylthio)pyridin-2-yl)piperidin-3-yl)acetic acid；AZD4017；AZD；2-[(3S)-1-[5-(cyclohexyl-carbamoyl)-6-propylsulfanyl-pyridin-2-yl]-3-piperidyl]acetic acid；2-[(3S)-1-[5-(cyclohexylcarbamoyl)-6-propylsulfanyl-pyridin-2-yl]-3-piperidyl]acetic acid；{(3s)-1-[5-(Cyclohexylcarbamoyl)-6-(Propylsulfanyl)pyridin-2-Yl]piperidin-3-Yl}acetic Acid
• CAS: 1024033-43-9
• 化学式: C₂₂H₃₃N₃O₃S
• 分子量: 419.588
• InChiKey: NCDZABJPWMBMIQ-INIZCTEOSA-N

物化性质

• 沸点：
  654.7±55.0 °C(Predicted)
• 密度：
  1.22±0.1 g/cm3(Predicted)
• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  108
• 氢给体数：
  2
• 氢受体数：
  6

安全信息

• 储存条件：
  存储条件：2-8°C，密封于干燥处。

制备方法与用途

AZD 4017 是一个有效的选择性11β-HSD1 抑制剂，其IC50值为7纳摩尔。

反应信息

• 作为产物：
  描述：

  6-chloro-N-cyclohexyl-2-propylsulfanylpyridine-3-carboxamide 在 水 、 potassium carbonate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 丁腈 为溶剂， 反应 5.0h， 生成 (S)-2-(1-(5-(环己基氨基甲酰基)-6-(丙硫基)吡啶-2-基)哌啶-3-基)乙酸
  参考文献：
  名称：

  Discovery of a Potent, Selective, and Orally Bioavailable Acidic 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD1) Inhibitor: Discovery of 2-[(3S)-1-[5-(Cyclohexylcarbamoyl)-6-propylsulfanylpyridin-2-yl]-3-piperidyl]acetic Acid (AZD4017)

  摘要：

  Inhibition of 11 beta-HSD1 is an attractive mechanism for the treatment of obesity and other elements of the metabolic syndrome. We report here the discovery of a nicotinic amide derived carboxylic acid class of inhibitors that has good potency, selectivity, and pharmacokinetic characteristics. Compound 11i (AZD4017) is an effective inhibitor of 11 beta-HSD1 in human adipocytes and exhibits good druglike properties and as a consequence was selected for clinical development.

  DOI：

  10.1021/jm300592r

文献信息

• CHEMICAL COMPOUNDS
  申请人：McCoull William

  公开号：US20080269288A1

  公开（公告）日：2008-10-30

  Compounds of formula (I): wherein variable groups are defined within; their use in the inhibition of 11βHSD1, processes for making them and pharmaceutical compositions comprising them are described.

  公式（I）的化合物：其中变量基团在内部定义；描述了它们在抑制11βHSD1中的应用，制备它们的过程以及包含它们的药物组合物。
• (S)-2-(1-(5-(CYCLOHEXYLCARBAMOYL)-6-(PROPYLTHIO)PYRIDIN-2-YL)PIPERIDIN-3-YL) ACETIC ACID FOR USE IN TREATING WOUNDS
  申请人：University of Leeds

  公开号：EP3821892A1

  公开（公告）日：2021-05-19

  The present specification relates to (S)-2-(1-(S-(cyclohexylcarbamoyl)-6-(propylthio)pyridin-2-yl)piperidin-3-yl)acetic acid (AZD4017), or a pharmaceutically acceptable salt thereof, for use in the treatment or prophylaxis of wounds, for example in diabetic patients. Methods of treatment and prophylaxis and the use of the compound in the preparation of a medicament for the treatment and prophylaxis of wounds are also provided.

  本说明书涉及(S)-2-(1-(S-(环己基氨基甲酰基)-6-(丙硫基)吡啶-2-基)哌啶-3-基)乙酸(AZD4017)或其药学上可接受的盐，用于治疗或预防伤口，例如糖尿病患者的伤口。此外，还提供了治疗和预防方法，以及该化合物在制备治疗和预防伤口的药物中的用途。
• HSD11B1 INHIBITORS FOR USE IN IMMUNOTHERAPY AND USES THEREOF
  申请人：UNIVERSITE DE GENEVE

  公开号：EP3878446A1

  公开（公告）日：2021-09-15

  The present invention relates to HSD11B1 inhibitors useful for increasing anti-tumor immune response in combination with immunotherapy, in particular for the treatment of cancers and to related compositions and methods using those.

  本发明涉及 HSD11B1 抑制剂，该抑制剂与免疫疗法结合使用可提高抗肿瘤免疫反应，特别是用于治疗癌症，本发明还涉及相关组合物和使用这些组合物的方法。
• AUTOMATED ASSESSMENT OF WOUND TISSUE
  申请人：Astrazeneca AB

  公开号：EP4002381A1

  公开（公告）日：2022-05-25

  A method of assessing a wound in a subject is provided. The method comprises obtaining one or more optical coherence tomography images of the wound and analysing the one or more optical coherence tomography images using a deep learning model that has been trained to classify pixels in an optical coherence tomography image of a wound between a plurality of classes comprising a plurality of classes associated with different types of wound tissue, thereby obtaining for each image analysed, an indication of the location of tissue likely to belong to each of the different types of wound tissue in the respective image.

  提供了一种评估受试者伤口的方法。该方法包括获取伤口的一个或多个光学相干断层扫描图像，并使用深度学习模型分析一个或多个光学相干断层扫描图像，该模型已被训练为在多个类别之间对伤口的光学相干断层扫描图像中的像素进行分类，这些类别包括与不同类型的伤口组织相关联的多个类别，从而获取所分析的每个图像中可能属于每个不同类型伤口组织的组织的位置指示。
• Methods and compositions for treating alcohol use disorders
  申请人：Sanna Pietro Paolo

  公开号：US10039772B2

  公开（公告）日：2018-08-07

  Disclosed are methods and compositions for treating alcohol dependence by administration to a patient of an inhibitor of 11β-hydroxysteroid dehydrogenases (11β-HSD) to modulate glucocorticoid effects. One such compound is the 11β-HSD inhibitor carbenoxolone (18β-glycyrrhetinic acid 3β-O-hemisuccinate), which has been extensively employed in the clinic for the treatment of gastritis and peptic ulcer. Carbenoxolone is active on both 11β-HSD1 and 2 isoforms. Here, carbenoxolone is surprisingly shown to reduce both baseline and excessive drinking in rats and mice. The carbenoxolone diastereomer 18α-glycyrrhetinic acid 3β-O-hemisuccinate (αCBX), which the applicants discovered to be selective for 11β-HSD2, was also effective in reducing alcohol drinking in mice. Thus, 11β-HSD inhibitors are a new class of candidate alcohol abuse medications and existing 11β-HSD inhibitor drugs may be re-purposed for alcohol abuse treatment.

  本发明公开了通过向患者施用 11β-羟基类固醇脱氢酶（11β-HSD）抑制剂以调节糖皮质激素作用来治疗酒精依赖症的方法和组合物。其中一种化合物是 11β-HSD 抑制剂卡本诺酮（18β-甘草次酸 3β-O-hemisuccinate ），临床上已广泛用于治疗胃炎和消化性溃疡。卡贝诺酮对 11β-HSD1 和 2 同工酶均有活性。令人惊讶的是，羧甲诺龙在大鼠和小鼠体内可减少基线饮酒量和过量饮酒量。申请人发现，羧诺龙的非对映异构体 18α-甘草次酸 3β-O-hemisuccinate (αCBX)对 11β-HSD2 具有选择性，也能有效减少小鼠的饮酒量。因此，11β-HSD 抑制剂是一类新的候选酗酒药物，现有的 11β-HSD 抑制剂药物可重新用于酗酒治疗。