Thiazole, 30 | 1154062-91-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: Thiazole, 30
• 英文别名: (2R)-2-hydroxy-3-[[4-[2-[4-(trifluoromethoxy)phenyl]-2-[4-[4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]ethyl]benzoyl]amino]propanoic acid
• CAS: 1154062-91-5
• 化学式: C₂₉H₂₂F₆N₂O₅S
• 分子量: 624.56
• InChiKey: NGUABMKOSJANPJ-SYIFMXBLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  43
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  137
• 氢给体数：
  3
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  methyl (2R)-2-hydroxy-3-[[4-[2-[4-(trifluoromethoxy)phenyl]-2-[4-[4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]ethyl]benzoyl]amino]propanoate 在 sodium hydroxide 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 Thiazole, 30
  参考文献：
  名称：

  Human Glucagon Receptor Antagonists with Thiazole Cores. A Novel Series with Superior Pharmacokinetic Properties

  摘要：

  The aim of the work presented here was to design and synthesize potent human glucagon receptor antagonists with improved pharmacokinetic (PK) properties for development of pharmaceuticals for the treatment of type 2 diabetes. We describe the preparation of compounds with cyclic cores (5-aminothiazoles), their binding affinities for the human glucagon and GIP receptors, as well as affinities for rat, mouse, pig, dog, and monkey glucagon receptors. Generally, the compounds had slightly less glucagon receptor affinity compared to compounds of the previous series, but this was compensated for by much improved PK profiles in both rats and dogs with high oral bioavailabilities and sustained high plasma exposures. The compounds generally showed species selectivity for glucagon receptor binding with poor affinities for the rat, mouse, rabbit, and pig receptors. However, dog and monkey glucagon receptor affinities seem to reflect the human situation. One compound of this series, 18, was tested intravenously in an anesthetized glucagon-challenged monkey model of hyperglucagonaemia and hyperglycaemia and was shown dose-dependently to decrease glycaemia. Further, high plasma exposures and a long plasma half-life (5.2 h) were obtained.

  DOI：

  10.1021/jm8016249