tert-butyl 4-({6-[5-(methylsulfonyl)-2,3-dihydro-1H-indol-1-yl]pyrimidin-4-yl}oxy)piperidine-1-carboxylate | 1145657-02-8

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: tert-butyl 4-({6-[5-(methylsulfonyl)-2,3-dihydro-1H-indol-1-yl]pyrimidin-4-yl}oxy)piperidine-1-carboxylate
• 英文别名: tert-butyl 4-({6-[5-(methylsulfonyl)indolin-1-yl]pyrimidin-4-yl}oxy)piperidine-1-carboxylate；4-[6-(5-methanesulfonyl-2,3-dihydro-indol-1-yl)-pyrimidin-4-yloxy]-piperidine-1-carbocyclic acid tert-butyl ester；4-[6-(5-methanesulfonyl-2,3-dihydro-indol-1-yl)-pyrimidin-4-yloxy]-piperidine-1-carboxylic acid tert-butyl ester；Tert-butyl 4-((6-(5-(methylsulfonyl)indolin-1-yl)pyrimidin-4-yl)oxy)piperidine-1-carboxylate；tert-butyl 4-[6-(5-methylsulfonyl-2,3-dihydroindol-1-yl)pyrimidin-4-yl]oxypiperidine-1-carboxylate
• CAS: 1145657-02-8
• 化学式: C₂₃H₃₀N₄O₅S
• 分子量: 474.581
• InChiKey: UVYUNHXMCYFXJW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  110
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-({6-[5-(methylsulfonyl)-2,3-dihydro-1H-indol-1-yl]pyrimidin-4-yl}oxy)piperidine-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 5-(methylsulfonyl)-1-[6-(piperidin-4-yloxy)pyrimidin-4-yl]-2,3-dihydro-1H-indole
  参考文献：
  名称：

  [EN] NEW COMPOUNDS, PHARMACEUTICAL COMPOSITION AND METHODS RELATING THERETO
  [FR] NOUVEAUX COMPOSÉS, COMPOSITION PHARMACEUTIQUE ET PROCÉDÉS S'Y RAPPORTANT

  摘要：

  本发明揭示了一种新的化合物，其在治疗患者的各种代谢相关疾病中具有用途。本发明的化合物具有结构（I）：其中X1、X2、X3、X4、Y1、Y2、A、R1、R2、R3、R4、m、n、p和q如本文所定义，包括立体异构体、酯、溶剂合物和其药用可接受盐。还揭示了含有本发明化合物的组合物与药用可接受载体的组合物，以及与其在患有相关疾病的患者中使用相关的方法。

  公开号：

  WO2010149685A1
• 作为产物：
  描述：

  5-(甲基磺酰基)-吲哚啉 在 sodium hydride 作用下， 以 四氢呋喃 、 乙醇 、 mineral oil 为溶剂， 反应 4.0h， 生成 tert-butyl 4-({6-[5-(methylsulfonyl)-2,3-dihydro-1H-indol-1-yl]pyrimidin-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

文献信息

• [EN] NEW COMPOUNDS, PHARMACEUTICAL COMPOSITION AND METHODS RELATING THERETO<br/>[FR] NOUVEAUX COMPOSÉS, COMPOSITION PHARMACEUTIQUE ET PROCÉDÉS S'Y RAPPORTANT
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2010149685A1

  公开（公告）日：2010-12-29

  New compounds are disclosed which have utility in the treatment of a variety of metabolic related conditions in a patient. The compounds of this invention have the structure (I): wherein X1, X2, X3, X4, Y1, Y2, A, R1, R2, R3, R4, m, n, p, and q are as defined herein, including stereoisomers, esters, solvates and pharmaceutically acceptable salts thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof in a patient in need thereof.

  本发明揭示了一种新的化合物，其在治疗患者的各种代谢相关疾病中具有用途。本发明的化合物具有结构（I）：其中X1、X2、X3、X4、Y1、Y2、A、R1、R2、R3、R4、m、n、p和q如本文所定义，包括立体异构体、酯、溶剂合物和其药用可接受盐。还揭示了含有本发明化合物的组合物与药用可接受载体的组合物，以及与其在患有相关疾病的患者中使用相关的方法。
• Pyrimidyl indoline compound
  申请人：Daiichi Sankyo Company, Limited

  公开号：US08232287B2

  公开（公告）日：2012-07-31

  It is intended to provide a pyrimidyl indoline compound which structurally differs from compounds used as active ingredients in conventional oral hypoglycemic agents and has excellent hypoglycemic effect. The present invention provides a compound represented by the general formula (I) or a pharmaceutically acceptable salt thereof:

  本发明旨在提供一种嘧啶基吲哚啉化合物，其在结构上与传统口服降糖药物中使用的活性成分有所不同，并具有出色的降糖效果。本发明提供一种由通式（I）表示的化合物或其药学上可接受的盐：
• Compounds, pharmaceutical composition and methods relating thereto
  申请人：Tran Joe A.

  公开号：US08481731B2

  公开（公告）日：2013-07-09

  New compounds are disclosed which have utility in the treatment of a variety of metabolic related conditions in a patient. The compounds of this invention have the structure (I): wherein X1, X2, X3, X4, Y1, Y2, A, R1, R2, R3, R4, m, n, p, and q are as defined herein, including stereoisomers, esters, and pharmaceutically acceptable salts thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof in a patient in need thereof.

  本发明揭示了一种新的化合物，可用于治疗患者的多种代谢相关疾病。本发明的化合物具有结构（I）：其中X1、X2、X3、X4、Y1、Y2、A、R1、R2、R3、R4、m、n、p和q的定义如本文所述，包括立体异构体、酯和其药学上可接受的盐。本发明还揭示了含有本发明化合物与药学上可接受的载体组合的组合物，以及与患者需要相关的使用方法。
• COMPOUNDS, PHARMACEUTICAL COMPOSITION AND METHODS RELATING THERETO
  申请人：TRAN Joe A.

  公开号：US20110021491A1

  公开（公告）日：2011-01-27

  New compounds are disclosed which have utility in the treatment of a variety of metabolic related conditions in a patient. The compounds of this invention have the structure (I): wherein X 1 , X 2 , X 3 , X 4 , Y 1 , Y 2 , A, R 1 , R 2 , R 3 , R 4 , m, n, p, and q are as defined herein, including stereoisomers, esters, and pharmaceutically acceptable salts thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof in a patient in need thereof.

  本发明揭示了新的化合物，其在治疗患者的多种代谢相关疾病方面具有实用性。该发明的化合物具有结构（I）：其中X1、X2、X3、X4、Y1、Y2、A、R1、R2、R3、R4、m、n、p和q如本文所定义，包括立体异构体、酯和其药物可接受的盐。本发明还揭示了含有该发明化合物与药物可接受载体组合的组合物，以及与患者需要的使用方法相关的方法。
• PYRIMIDYL INDOLINE COMPOUND
  申请人：Daiichi Sankyo Company, Limited

  公开号：EP2210886B1

  公开（公告）日：2015-09-23