[4-(2,5-dichloro-phenoxy)-pyrimidin-5-yl]-(4-methyl-3,4-dihydro-2H-quinoxalin-1-yl)-methanone | 1315469-40-9

• 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)-pyrimidin-5-yl]-(4-methyl-3,4-dihydro-2H-quinoxalin-1-yl)-methanone
• 英文别名: [4-(2,5-dichlorophenoxy)pyrimidin-5-yl]-(4-methyl-2,3-dihydroquinoxalin-1-yl)methanone
• CAS: 1315469-40-9
• 化学式: C₂₀H₁₆Cl₂N₄O₂
• 分子量: 415.279
• InChiKey: NHEYHWKFXOLIOV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  58.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2,5-二氯苯酚 在 氯化亚砜 、 sodium hydride 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 [4-(2,5-dichloro-phenoxy)-pyrimidin-5-yl]-(4-methyl-3,4-dihydro-2H-quinoxalin-1-yl)-methanone
  参考文献：
  名称：

  Discovery of novel pyrimidine and malonamide derivatives as TGR5 agonists

  摘要：

  Takeda G-protein-coupled receptor 5 (TGR5) is a promising molecular target for metabolic diseases. A series of 4-(2,5-dichlorophenoxy)pyrimidine and cyclopropylmalonamide derivatives were synthesized as potent agonists of TGR5 based on a bioisosteric replacement strategy. Several compounds exhibited improved potency, compared to a reference compound with a pyridine scaffold. The pharmacokinetic profile of the representative compound 18 was considered moderate.

  DOI：

  10.1016/j.bmcl.2014.07.026
• 作为试剂：
  描述：

  4-(2,5-dichlorophenoxy)pyrimidine-5-carboxylate 、 1-甲基-1,2,3,4-四氢喹喔啉二盐酸盐 、 左旋肉碱 在 [4-(2,5-dichloro-phenoxy)-pyrimidin-5-yl]-(4-methyl-3,4-dihydro-2H-quinoxalin-1-yl)-methanone 作用下， 以to give 6.5 mg (8%) of the desired compound的产率得到[4-(2,5-dichloro-phenoxy)-pyrimidin-5-yl]-(4-methyl-3,4-dihydro-2H-quinoxalin-1-yl)-methanone
  参考文献：
  名称：

  4-phenoxy-nicotinamide or 4-phenoxy-pyrimidine-5-carboxamide compounds

  摘要：

  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。

  公开号：

  US08420647B2

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：US20110178089A1

  公开（公告）日：2011-07-21

  This invention relates to novel phenyl amide or pyridyl amide derivatives of the formula wherein A 1 , A 2 , B 1 , B 2 and R 1 to R 11 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.

  这项发明涉及公式的新型苯基酰胺或吡啶基酰胺衍生物 其中A 1 ，A 2 ，B 1 ，B 2 和R 1 到R 11 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，可用作治疗诸如2型糖尿病等疾病的药物。
• 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
• Discovery of novel pyrimidine and malonamide derivatives as TGR5 agonists
  作者：Eun Ju Park、Young Gil Ahn、Seung Hyun Jung、Hyo Jeong Bang、Mira Kim、Dong Jin Hong、Jisook Kim、Kwee Hyun Suh、Young Jin Kim、Doran Kim、Eun-Yeong Kim、Kiho Lee、Kyung Hoon Min

  DOI：10.1016/j.bmcl.2014.07.026

  日期：2014.9

  Takeda G-protein-coupled receptor 5 (TGR5) is a promising molecular target for metabolic diseases. A series of 4-(2,5-dichlorophenoxy)pyrimidine and cyclopropylmalonamide derivatives were synthesized as potent agonists of TGR5 based on a bioisosteric replacement strategy. Several compounds exhibited improved potency, compared to a reference compound with a pyridine scaffold. The pharmacokinetic profile of the representative compound 18 was considered moderate.