5-(2-chloro-6-(1-(4-chlorophenylsulfonyl)-1,2,3,4-tetrahydroquinolin-7-yloxy)pyridin-4-yl)-3-cyclopropyl-1,2,4-oxadiazole | 1562443-03-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-(2-chloro-6-(1-(4-chlorophenylsulfonyl)-1,2,3,4-tetrahydroquinolin-7-yloxy)pyridin-4-yl)-3-cyclopropyl-1,2,4-oxadiazole
• 英文别名: 5-[2-chloro-6-[[1-(4-chlorophenyl)sulfonyl-3,4-dihydro-2H-quinolin-7-yl]oxy]pyridin-4-yl]-3-cyclopropyl-1,2,4-oxadiazole
• CAS: 1562443-03-1
• 化学式: C₂₅H₂₀Cl₂N₄O₄S
• 分子量: 543.43
• InChiKey: KLWDSSAFOHVCAT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  107
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  7-羟基-1,2,3,4-四氢喹啉 、 4-氯苯磺酰氯 在 吡啶 、 potassium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 5-(2-chloro-6-(1-(4-chlorophenylsulfonyl)-1,2,3,4-tetrahydroquinolin-7-yloxy)pyridin-4-yl)-3-cyclopropyl-1,2,4-oxadiazole
  参考文献：
  名称：

  Discovery and optimization of 5-(2-((1-(phenylsulfonyl)-1,2,3,4-tetrahydroquinolin-7-yl)oxy)pyridin-4-yl)-1,2,4-oxadiazoles as novel gpr119 agonists

  摘要：

  We describe the discovery and optimization of 5-(2-((1-(phenylsulfonyl)-1,2,3,4-tetrahydroquinolin-7-yl)oxy)pyridin-4-yl)-1,2,4-oxadiazoles as novel agonists of GPR119. Previously described aniline 2 had suboptimal efficacy in signaling assays using cynomolgus monkey (cyno) GPR119 making evaluation of the target in preclinical models difficult. Replacement of the aniline ring with a tetrahydroquinoline ring constrained the rotation of the aniline C-N bond and gave compounds with increased efficacy on human and cyno receptors. Additional optimization led to the discovery of 10, which possesses higher free fraction in plasma and improved pharmacokinetic properties in rat and cyno compared to 2. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.12.127

文献信息

• Discovery and optimization of 5-(2-((1-(phenylsulfonyl)-1,2,3,4-tetrahydroquinolin-7-yl)oxy)pyridin-4-yl)-1,2,4-oxadiazoles as novel gpr119 agonists
  作者：Yingcai Wang、Ming Yu、Jiang Zhu、Jian (Ken) Zhang、Frank Kayser、Julio C. Medina、Karen Siegler、Marion Conn、Bei Shan、Mark P. Grillo、Jiwen (Jim) Liu、Peter Coward

  DOI：10.1016/j.bmcl.2013.12.127

  日期：2014.2

  We describe the discovery and optimization of 5-(2-((1-(phenylsulfonyl)-1,2,3,4-tetrahydroquinolin-7-yl)oxy)pyridin-4-yl)-1,2,4-oxadiazoles as novel agonists of GPR119. Previously described aniline 2 had suboptimal efficacy in signaling assays using cynomolgus monkey (cyno) GPR119 making evaluation of the target in preclinical models difficult. Replacement of the aniline ring with a tetrahydroquinoline ring constrained the rotation of the aniline C-N bond and gave compounds with increased efficacy on human and cyno receptors. Additional optimization led to the discovery of 10, which possesses higher free fraction in plasma and improved pharmacokinetic properties in rat and cyno compared to 2. (C) 2014 Elsevier Ltd. All rights reserved.