tert-butyl 4-({2-[5-(methylsulfonyl)-2,3-dihydro-1H-indol-1-yl]pyridin-4-yl}oxy)piperidine-1-carboxylate | 1570178-89-0

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: tert-butyl 4-({2-[5-(methylsulfonyl)-2,3-dihydro-1H-indol-1-yl]pyridin-4-yl}oxy)piperidine-1-carboxylate
• CAS: 1570178-89-0
• 化学式: C₂₄H₃₁N₃O₅S
• 分子量: 473.593
• InChiKey: KFAPJMAWJRJVLQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.96
• 重原子数：
  33.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  89.04
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-({2-[5-(methylsulfonyl)-2,3-dihydro-1H-indol-1-yl]pyridin-4-yl}oxy)piperidine-1-carboxylate 在 盐酸 、 sodium hydroxide 作用下， 以 甲醇 、 乙酸乙酯 、 水 为溶剂， 反应 16.0h， 以1.84 g的产率得到5-(methylsulfonyl)-1-[4-(piperidin-4-yloxy)pyridin-2-yl]-2,3-dihydro-1H-indole
  参考文献：
  名称：

  Discovery of a novel series of indoline carbamate and indolinylpyrimidine derivatives as potent GPR119 agonists

  摘要：

  GPR119 has emerged as an attractive target for anti-diabetic agents. We identified a structurally novel GPR119 agonist 22c that carries a 5-(methylsulfonyl) indoline motif as an early lead compound. To generate more potent compounds of this series, structural modifications were performed mainly to the central alkylene spacer. Installation of a carbonyl group and a methyl group on this spacer significantly enhanced agonistic activity, resulting in the identification of 2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl] propyl 7-fluoro-5-(methylsulfonyl)-2,3-dihydro-1H-indole-1-carboxylate (20). To further expand the chemical series of indoline-based GPR119 agonists, several heterocyclic core systems were introduced as surrogates of the carbamate spacer that mimic the presumed active conformation. This approach successfully produced an indolinylpyrimidine derivative 37, 5-(methylsulfonyl)-1-[6-({1-[3-(propan-2-yl)-1,2,4-oxadiazol-5-yl]piperidin-4-yl}oxy)pyrimidin-4-yl]-2,3-dihydro-1H-indole, which has potent GPR119 agonist activity. In rat oral glucose tolerance tests, these two indoline-based compounds effectively lowered plasma glucose excursion and glucose-dependent insulin secretion after oral administration. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.01.028
• 作为产物：
  描述：

  4-(甲苯-4-磺酰氧)哌啶-1-羧酸叔丁酯 在 tris-(dibenzylideneacetone)dipalladium(0) 、 potassium carbonate 、 caesium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 32.0h， 生成 tert-butyl 4-({2-[5-(methylsulfonyl)-2,3-dihydro-1H-indol-1-yl]pyridin-4-yl}oxy)piperidine-1-carboxylate
  参考文献：
  名称：

  Discovery of a novel series of indoline carbamate and indolinylpyrimidine derivatives as potent GPR119 agonists

  摘要：

  GPR119 has emerged as an attractive target for anti-diabetic agents. We identified a structurally novel GPR119 agonist 22c that carries a 5-(methylsulfonyl) indoline motif as an early lead compound. To generate more potent compounds of this series, structural modifications were performed mainly to the central alkylene spacer. Installation of a carbonyl group and a methyl group on this spacer significantly enhanced agonistic activity, resulting in the identification of 2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl] propyl 7-fluoro-5-(methylsulfonyl)-2,3-dihydro-1H-indole-1-carboxylate (20). To further expand the chemical series of indoline-based GPR119 agonists, several heterocyclic core systems were introduced as surrogates of the carbamate spacer that mimic the presumed active conformation. This approach successfully produced an indolinylpyrimidine derivative 37, 5-(methylsulfonyl)-1-[6-({1-[3-(propan-2-yl)-1,2,4-oxadiazol-5-yl]piperidin-4-yl}oxy)pyrimidin-4-yl]-2,3-dihydro-1H-indole, which has potent GPR119 agonist activity. In rat oral glucose tolerance tests, these two indoline-based compounds effectively lowered plasma glucose excursion and glucose-dependent insulin secretion after oral administration. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.01.028