2-[(3R)-1-[5-(cyclohexylcarbamoyl)-6-propylsulfanylpyridin-2-yl]-3-piperidyl]acetic acid | 1024033-31-5

• 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
• 英文名称: 2-[(3R)-1-[5-(cyclohexylcarbamoyl)-6-propylsulfanylpyridin-2-yl]-3-piperidyl]acetic acid
• 英文别名: 2-[(3R)-1-[5-(cyclohexylcarbamoyl)-6-propylsulfanylpyridin-2-yl]piperidin-3-yl]acetic acid
• CAS: 1024033-31-5
• 化学式: C₂₂H₃₃N₃O₃S
• 分子量: 419.588
• InChiKey: NCDZABJPWMBMIQ-MRXNPFEDSA-N

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

反应信息

• 作为产物：
  描述：

  2,6-二氯烟酸 在 氯化亚砜 、 水 、 sodium hexamethyldisilazane 、 potassium carbonate 、 N,N-二甲基甲酰胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 丁腈 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.17h， 生成 2-[(3R)-1-[5-(cyclohexylcarbamoyl)-6-propylsulfanylpyridin-2-yl]-3-piperidyl]acetic acid
  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。
• FXR agonist compositions for combination therapy
  申请人：Intercept Pharmaceuticals, Inc.

  公开号：US10894054B2

  公开（公告）日：2021-01-19

  The present application relates to a pharmaceutical composition comprising a combination of an FXR agonist and at least one additional therapeutic agent that lowers the glucose level in the blood, stimulates insulin secretion, and/or increases insulin sensitivity. The present application relates to use of the pharmaceutical composition for the treatment or prevention of a FXR mediated disease or condition, such as NAFLD and NASH, a disease or condition related to an elevated level of glucose in the blood, decreased secretion of insulin, and/or decreased insulin sensitivity such as hyperglycemia, diabetes, obesity, and insulin resistance, or for lowering the glucose level in the blood, stimulating insulin secretion, and/or increasing insulin sensitivity.

  本申请涉及一种药物组合物，其包含一种FXR激动剂和至少一种额外治疗剂的组合，该治疗剂可降低血液中的葡萄糖水平、刺激胰岛素分泌和/或增加胰岛素敏感性。本申请涉及该药物组合物用于治疗或预防FXR介导的疾病或病症，如非酒精性脂肪肝和NASH，与血液中葡萄糖水平升高、胰岛素分泌减少和/或胰岛素敏感性降低有关的疾病或病症，如高血糖、糖尿病、肥胖和胰岛素抵抗，或用于降低血液中葡萄糖水平、刺激胰岛素分泌和/或增加胰岛素敏感性。
• PYRIDINE CARBOXAMIDES AS 11-BETA-HSD1 INHIBITORS
  申请人：AstraZeneca AB

  公开号：EP2086939B8

  公开（公告）日：2011-06-22
• Chemical compounds
  申请人：AstraZeneca AB

  公开号：EP2233480B1

  公开（公告）日：2013-05-29
• PHARMACEUTICAL COMPOSITIONS FOR COMBINATION THERAPY
  申请人：Intercept Pharmaceuticals, Inc.

  公开号：US20180117065A1

  公开（公告）日：2018-05-03

  The present application relates to a pharmaceutical composition comprising a combination of an FXR agonist and at least one additional therapeutic agent that lowers the glucose level in the blood, stimulates insulin secretion, and/or increases insulin sensitivity. The present application relates to use of the pharmaceutical composition for the treatment or prevention of a FXR mediated disease or condition, such as NAFLD and NASH, a disease or condition related to an elevated level of glucose in the blood, decreased secretion of insulin, and/or decreased insulin sensitivity such as hyperglycemia, diabetes, obesity, and insulin resistance, or for lowering the glucose level in the blood, stimulating insulin secretion, and/or increasing insulin sensitivity.