tert-butyl 4-{4-[5-(methylsulfonyl)-2,3-dihydro-1H-indol-1-yl]-4-oxobutyl}piperidine-1-carboxylate | 1570178-46-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: tert-butyl 4-{4-[5-(methylsulfonyl)-2,3-dihydro-1H-indol-1-yl]-4-oxobutyl}piperidine-1-carboxylate
• 英文别名: Tert-butyl 4-[4-(5-methylsulfonyl-2,3-dihydroindol-1-yl)-4-oxobutyl]piperidine-1-carboxylate；tert-butyl 4-[4-(5-methylsulfonyl-2,3-dihydroindol-1-yl)-4-oxobutyl]piperidine-1-carboxylate
• CAS: 1570178-46-9
• 化学式: C₂₃H₃₄N₂O₅S
• 分子量: 450.599
• InChiKey: FZKCUJSOEZZNTM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  92.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-(甲基磺酰基)-吲哚啉 、 4-(N-Boc-4-哌啶基)丁酸 在 三乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以50%的产率得到tert-butyl 4-{4-[5-(methylsulfonyl)-2,3-dihydro-1H-indol-1-yl]-4-oxobutyl}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

文献信息

• Discovery of a novel series of indoline carbamate and indolinylpyrimidine derivatives as potent GPR119 agonists
  作者：Kenjiro Sato、Hiromichi Sugimoto、Kentaro Rikimaru、Hiroshi Imoto、Masahiro Kamaura、Nobuyuki Negoro、Yoshiyuki Tsujihata、Hirohisa Miyashita、Tomoyuki Odani、Toshiki Murata

  DOI：10.1016/j.bmc.2014.01.028

  日期：2014.3

  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.