tert-butyl (S)-(1-oxo-3-phenyl-1-((5-(pyridin-4-yl)-4H-1,2,4-triazol-3-yl)amino)propan-2-yl)(thiazol-5-ylmethyl)carbamate | 1442476-83-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: tert-butyl (S)-(1-oxo-3-phenyl-1-((5-(pyridin-4-yl)-4H-1,2,4-triazol-3-yl)amino)propan-2-yl)(thiazol-5-ylmethyl)carbamate
• CAS: 1442476-83-6
• 化学式: C₂₅H₂₇N₇O₃S
• 分子量: 505.6
• InChiKey: BWVKTQICHVYTRR-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.31
• 重原子数：
  36.0
• 可旋转键数：
  8.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  125.99
• 氢给体数：
  2.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  tert-butyl (S)-(1-oxo-3-phenyl-1-((5-(pyridin-4-yl)-4H-1,2,4-triazol-3-yl)amino)propan-2-yl)(thiazol-5-ylmethyl)carbamate 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.5h， 以35%的产率得到(S)-3-phenyl-N-(5-(pyridin-4-yl)-4H-1,2,4-triazol-3-yl)-2-((thiazol-5-ylmethyl)amino)propanamide
  参考文献：
  名称：

  Aminopyrazole–Phenylalanine Based GPR142 Agonists: Discovery of Tool Compound and in Vivo Efficacy Studies

  摘要：

  Herein, we report the lead optimization of amrinone-phenylalanine based GPR142 agonists. Structure-activity relationship studies led to the discovery of aminopyrazole-phenylalanine carboxylic acid 22, which exhibited good agonistic activity, high target selectivity, desirable pharmacokinetic properties, and no cytochrome P450 or hERG liability. Compound 22, together with its orally bioavailable ethyl ester prodrug 23, were found to be suitable for in vivo proof-of-concept studies. Compound 23 displayed good efficacy in a mouse oral glucose tolerance test (OGTT). Compound 22 showed GPR142 dependent stimulation of insulin secretion in isolated mouse islets and demonstrated a statistically significant glucose lowering effect in a mouse model bearing transplanted human islets.

  DOI：

  10.1021/ml4000854
• 作为产物：
  描述：

  N-叔丁氧羰基-L-苯丙氨酸甲酯 在 吡啶 、 三聚氟氰 、 sodium hydride 、 三乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 生成 tert-butyl (S)-(1-oxo-3-phenyl-1-((5-(pyridin-4-yl)-4H-1,2,4-triazol-3-yl)amino)propan-2-yl)(thiazol-5-ylmethyl)carbamate
  参考文献：
  名称：

  Aminopyrazole–Phenylalanine Based GPR142 Agonists: Discovery of Tool Compound and in Vivo Efficacy Studies

  摘要：

  Herein, we report the lead optimization of amrinone-phenylalanine based GPR142 agonists. Structure-activity relationship studies led to the discovery of aminopyrazole-phenylalanine carboxylic acid 22, which exhibited good agonistic activity, high target selectivity, desirable pharmacokinetic properties, and no cytochrome P450 or hERG liability. Compound 22, together with its orally bioavailable ethyl ester prodrug 23, were found to be suitable for in vivo proof-of-concept studies. Compound 23 displayed good efficacy in a mouse oral glucose tolerance test (OGTT). Compound 22 showed GPR142 dependent stimulation of insulin secretion in isolated mouse islets and demonstrated a statistically significant glucose lowering effect in a mouse model bearing transplanted human islets.

  DOI：

  10.1021/ml4000854