[4-(2,5-dichloro-phenoxy)-pyridin-3-yl]-(3,4-dihydro-2H-quinolin-1-yl)-methanone | 1315468-50-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [4-(2,5-dichloro-phenoxy)-pyridin-3-yl]-(3,4-dihydro-2H-quinolin-1-yl)-methanone
• 英文别名: [4-(2,5-dichlorophenoxy)pyridin-3-yl]-(3,4-dihydro-2H-quinolin-1-yl)methanone
• CAS: 1315468-50-8
• 化学式: C₂₁H₁₆Cl₂N₂O₂
• 分子量: 399.276
• InChiKey: HHJXDGCDWSETDB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  42.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  [4-(2,5-dichloro-phenoxy)-pyridin-3-yl]-(3,4-dihydro-2H-quinolin-1-yl)-methanone 在 间氯过氧苯甲酸 、 碳酸氢钠 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 2.75h， 以99%的产率得到[4-(2,5-dichloro-phenoxy)-1-oxy-pyridin-3-yl]-(3,4-dihydro-2H-quinolin-1-yl)-methanone
  参考文献：
  名称：

  [EN] 4-PHENOXY-NICOTINAMIDE OR 4-PHENOXY-PYRIMIDINE-5-CARBOXAMIDE COMPOUNDS
  [FR] COMPOSÉS DE 4-PHÉNOXYNICOTINAMIDE OU DE 4-PHÉNOXY-PYRIMIDINE-5-CARBOXAMIDE

  摘要：

  这项发明涉及公式（I）中的新型苯基酰胺或吡啶基酰胺衍生物，其中A1、A2、B1、B2和R1至R11如描述和索赔中所定义，并且其药学上可接受的盐。这些化合物是GPBAR1激动剂，可用作治疗疾病如2型糖尿病的药物。

  公开号：

  WO2011089099A1
• 作为产物：
  描述：

  2,5-二氯苯酚 在 copper(l) iodide 、 铜 、 potassium carbonate 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 26.0h， 生成 [4-(2,5-dichloro-phenoxy)-pyridin-3-yl]-(3,4-dihydro-2H-quinolin-1-yl)-methanone
  参考文献：
  名称：

  [EN] 4-PHENOXY-NICOTINAMIDE OR 4-PHENOXY-PYRIMIDINE-5-CARBOXAMIDE COMPOUNDS
  [FR] COMPOSÉS DE 4-PHÉNOXYNICOTINAMIDE OU DE 4-PHÉNOXY-PYRIMIDINE-5-CARBOXAMIDE

  摘要：

  这项发明涉及公式（I）中的新型苯基酰胺或吡啶基酰胺衍生物，其中A1、A2、B1、B2和R1至R11如描述和索赔中所定义，并且其药学上可接受的盐。这些化合物是GPBAR1激动剂，可用作治疗疾病如2型糖尿病的药物。

  公开号：

  WO2011089099A1

文献信息

• [EN] 4-PHENOXY-NICOTINAMIDE OR 4-PHENOXY-PYRIMIDINE-5-CARBOXAMIDE COMPOUNDS<br/>[FR] COMPOSÉS DE 4-PHÉNOXYNICOTINAMIDE OU DE 4-PHÉNOXY-PYRIMIDINE-5-CARBOXAMIDE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2011089099A1

  公开（公告）日：2011-07-28

  This invention relates to novel phenyl amide or pyridyl amide derivatives of the formula (I), wherein A1, A2, B1, B2 and R1 to R11 are as defined in the description and in the claims, as well as pharmaceutically acceptable salts thereof. These compounds are GPBAR1 agonists and can be used as medicaments for the treatment of diseases such as type II diabetes.

  这项发明涉及公式（I）中的新型苯基酰胺或吡啶基酰胺衍生物，其中A1、A2、B1、B2和R1至R11如描述和索赔中所定义，并且其药学上可接受的盐。这些化合物是GPBAR1激动剂，可用作治疗疾病如2型糖尿病的药物。
• 4-phenoxy-nicotinamide or 4-phenoxy-pyrimidine-5-carboxamide compounds
  申请人：Bissantz Caterina

  公开号：US08420647B2

  公开（公告）日：2013-04-16

  This invention relates to novel phenyl amide or pyridyl amide derivatives of the formula wherein A1, A2, B1, B2 and R1 to R11 are as defined in the description and in the claims, as well as pharmaceutically acceptable salts thereof. These compounds are GPBAR1 agonists and can be used as medicaments for the treatment of diseases such as type II diabetes.

  本发明涉及以下式子的新型苯酰胺或吡啶酰胺衍生物： 其中A1、A2、B1、B2和R1到R11如描述和权利要求中所定义，并且其药学上可接受的盐。这些化合物是GPBAR1激动剂，可用作治疗二型糖尿病等疾病的药物。
• Design, Synthesis, and Antidiabetic Activity of 4-Phenoxynicotinamide and 4-Phenoxypyrimidine-5-carboxamide Derivatives as Potent and Orally Efficacious TGR5 Agonists
  作者：Hongliang Duan、Mengmeng Ning、Xiaoyan Chen、Qingan Zou、Liming Zhang、Ying Feng、Lina Zhang、Ying Leng、Jianhua Shen

  DOI：10.1021/jm301071h

  日期：2012.12.13

  4-Phenoxynicotinamide and 4-phenoxypyrimidine-5-carboxamide derivatives as potent and orally efficacious TGR5 agonists are reported. Several 4-phenoxynicotinamide derivatives were found to activate human and mouse TGR5 (hTGR5 and mTGR5) with EC50 values in the low nanomolar range. Compound 23g, with an EC50 value of 0.72 nM on hTGR5 and an EC50 value of 6.2 nM on mTGR5, was selected for further in vivo efficacy studies. This compound exhibited a significant dose-dependent glucagon-like peptide-1 (GLP-1) secretion effect. A single oral dose of 23g (50 mg/kg) significantly reduced blood glucose levels in db/db mice and caused a 49% reduction in the area under the blood glucose curve (AUC)(0-120) (min) following an oral glucose tolerance test (OGTT) in imprinting control region (ICR) mice. However, 23g stimulated gallbladder filling, which might result in side effects to the gallbladder.
• US8420647B2
  申请人：——

  公开号：US8420647B2

  公开（公告）日：2013-04-16
• US8729091B2
  申请人：——

  公开号：US8729091B2

  公开（公告）日：2014-05-20