tert-butyl {(3R)-1-[3-(2-chlorobenzyl)-6-methoxy-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinolin-2-yl]piperidin-3-yl}carbamate | 1349877-59-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: tert-butyl {(3R)-1-[3-(2-chlorobenzyl)-6-methoxy-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinolin-2-yl]piperidin-3-yl}carbamate
• 英文别名: tert-butyl N-[(3R)-1-[3-[(2-chlorophenyl)methyl]-6-methoxy-5-methyl-4-oxoimidazo[4,5-c]quinolin-2-yl]piperidin-3-yl]carbamate
• CAS: 1349877-59-3
• 化学式: C₂₉H₃₄ClN₅O₄
• 分子量: 552.073
• InChiKey: FYTFGYXKEXEMTN-LJQANCHMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  39
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  88.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl {(3R)-1-[3-(2-chlorobenzyl)-6-methoxy-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinolin-2-yl]piperidin-3-yl}carbamate 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.0h， 生成 2-[(3R)-3-aminopiperidin-1-yl]-3-(2-chlorobenzyl)-6-methoxy-5-methyl-3,5-dihydro-4H-imidazo[4,5-c]quinolin-4-one hydrochloride
  参考文献：
  名称：

  3 H-咪唑并[4,5 - c ]喹啉-4（5 H）-ones作为有效的和选择性的二肽基肽酶IV（DPP-4）抑制剂的发现

  摘要：

  近年来，二肽基肽酶IV抑制剂被认为是治疗2型糖尿病的有价值的药物。在这里，我们报告发现一种新型有效的DPP-4抑制剂，其3 H-咪唑并[4,5- c ]喹啉4（5 H）-一个为骨架。使用对接研究对前导化合物2a在7位和8位进行高效优化后，我们发现28种新型DPP-4抑制剂具有对各种DPP-4同源物的优异选择性。化合物28与市售DPP-4抑制剂相比，具有较强的DPP-4抑制活性。我们还发现7位羧基可以与Lys554残基相互作用形成盐桥。另外，将羧基引入7位导致活性增强并且降低了hERG通道抑制和诱导的磷脂中毒的风险。在合成具有7个羧基的化合物时，我们在分子内钯偶联反应中使用大体积酯实现了高效的区域选择性合成。

  DOI：

  10.1016/j.bmc.2012.07.046
• 作为产物：
  描述：

  tert-butyl N-[(3R)-1-[1-[(2-chlorophenyl)methyl]-4-iodo-5-[(2-methoxyphenyl)-methylcarbamoyl]imidazol-2-yl]piperidin-3-yl]carbamate 在 palladium diacetate 、 三苯基膦 、 silver carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.83h， 以70%的产率得到tert-butyl {(3R)-1-[3-(2-chlorobenzyl)-6-methoxy-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinolin-2-yl]piperidin-3-yl}carbamate
  参考文献：
  名称：

  Preparation of 2-aminosubstituted 3H-imidazo[4,5-c]quinolin-4(5H)-ones by palladium-assisted internal biaryl coupling reaction

  摘要：

  Representatives of the 3H-imidazo[4,5-c]quinolin-4(5H)-ones have shown interesting biological activity. We have found 2-aminosubstituted 3H-imidazo[4,5-c]quinolin-4(5H)-one as a potent dipeptidyl peptidase 4 inhibitor. However effective synthesis of this nucleus with various substituents at the 6-9-positions has not been reported. We report herein the development of a novel and efficient synthesis of 2-aminosubstituted 3H-imidazo[4,5-c]quinolin-4(5H)-ones by palladium-assisted internal biaryl coupling reaction. Our optimization of the reaction conditions revealed that the most important factors for this reaction are use of silver carbonate as a base and high reaction temperature. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2011.10.015

文献信息

• Discovery of 3H-imidazo[4,5-c]quinolin-4(5H)-ones as potent and selective dipeptidyl peptidase IV (DPP-4) inhibitors
  作者：Yohei Ikuma、Hitoshi Hochigai、Hidenori Kimura、Noriko Nunami、Tomonori Kobayashi、Katsuya Uchiyama、Yudai Furuta、Mutsuko Sakai、Masakuni Horiguchi、Yumi Masui、Kazuhiko Okazaki、Yasuhiro Sato、Hiroyuki Nakahira

  DOI：10.1016/j.bmc.2012.07.046

  日期：2012.10

  years, dipeptidyl peptidase IV inhibitors have been noted as valuable agents for treatment of type 2 diabetes. Herein, we report the discovery of a novel potent DPP-4 inhibitor with 3H-imidazo[4,5-c]quinolin-4(5H)-one as skeleton. After efficient optimization of the lead compound 2a at the 7- and 8-positions using a docking study, we found 28 as a novel DPP-4 inhibitor with excellent selectivity against

  近年来，二肽基肽酶IV抑制剂被认为是治疗2型糖尿病的有价值的药物。在这里，我们报告发现一种新型有效的DPP-4抑制剂，其3 H-咪唑并[4,5- c ]喹啉4（5 H）-一个为骨架。使用对接研究对前导化合物2a在7位和8位进行高效优化后，我们发现28种新型DPP-4抑制剂具有对各种DPP-4同源物的优异选择性。化合物28与市售DPP-4抑制剂相比，具有较强的DPP-4抑制活性。我们还发现7位羧基可以与Lys554残基相互作用形成盐桥。另外，将羧基引入7位导致活性增强并且降低了hERG通道抑制和诱导的磷脂中毒的风险。在合成具有7个羧基的化合物时，我们在分子内钯偶联反应中使用大体积酯实现了高效的区域选择性合成。
• Preparation of 2-aminosubstituted 3H-imidazo[4,5-c]quinolin-4(5H)-ones by palladium-assisted internal biaryl coupling reaction
  作者：Yohei Ikuma、Hiroyuki Nakahira

  DOI：10.1016/j.tet.2011.10.015

  日期：2011.12

  Representatives of the 3H-imidazo[4,5-c]quinolin-4(5H)-ones have shown interesting biological activity. We have found 2-aminosubstituted 3H-imidazo[4,5-c]quinolin-4(5H)-one as a potent dipeptidyl peptidase 4 inhibitor. However effective synthesis of this nucleus with various substituents at the 6-9-positions has not been reported. We report herein the development of a novel and efficient synthesis of 2-aminosubstituted 3H-imidazo[4,5-c]quinolin-4(5H)-ones by palladium-assisted internal biaryl coupling reaction. Our optimization of the reaction conditions revealed that the most important factors for this reaction are use of silver carbonate as a base and high reaction temperature. (C) 2011 Elsevier Ltd. All rights reserved.