tert-butyl {(3R)-1-[3-(2-chlorobenzyl)-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinolin-2-yl]piperidin-3-yl}-carbamate | 853069-26-8

• 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)-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]-4-oxo-5H-imidazo[4,5-c]quinolin-2-yl]piperidin-3-yl]carbamate
• CAS: 853069-26-8
• 化学式: C₂₇H₃₀ClN₅O₃
• 分子量: 508.02
• InChiKey: BCEQTNVFBHOLFH-GOSISDBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  88.5
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl {(3R)-1-[3-(2-chlorobenzyl)-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinolin-2-yl]piperidin-3-yl}-carbamate 在 盐酸 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 生成 C₂₅H₂₈ClN₅O*ClH
  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：

  2-氯苄溴 在 四(三苯基膦)钯 、 二碘甲烷 、 铁粉 、 sodium hydride 、 sodium carbonate 、 potassium carbonate 、 溶剂黄146 、 亚硝酸异戊酯 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 水 、 甲苯 、 乙腈 、 mineral oil 为溶剂， 反应 87.5h， 生成 tert-butyl {(3R)-1-[3-(2-chlorobenzyl)-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

• NOVEL CONDENSED IMIDAZOLE DERIVATIVE
  申请人：Dainippon Sumitomo Pharma Co., Ltd.

  公开号：EP1690863A1

  公开（公告）日：2006-08-16

  Disclosed is a compound represented by the formula (1) below which has a high DPP-IV inhibitory activity and is improved in safety, toxicity and the like. Also disclosed is a prodrug of such a compound and pharmaceutically acceptable salts of them. (In the formula, R1 represents a hydrogen atom, an optionally substituted alkyl group or the like; R2 and R3 independently represent a hydrogen atom, an optionally substituted alkyl group or the like; R4 and R5 independently represent a hydrogen atom, an optionally substituted alkyl group or the like: R6 represents a hydrogen atom, an optionally substituted aryl group or the like; and -Y-NH2, represents a group represented by the following formula (A): (wherein m is 0, 1 or 2; and R7 may not exist or one or two R7 may exist and independently represent an optionally substituted alkyl group or the like) or the like.]

  揭示了一种化合物，其化学式如下（1），具有较高的DPP-IV抑制活性，并在安全性、毒性等方面得到改善。还披露了这种化合物的前药和其药用可接受的盐。（在该式中，R1代表氢原子、可选择取代的烷基或类似物；R2和R3独立代表氢原子、可选择取代的烷基或类似物；R4和R5独立代表氢原子、可选择取代的烷基或类似物；R6代表氢原子、可选择取代的芳基或类似物；-Y-NH2代表由以下式（A）表示的基团：（其中m为0、1或2；R7可能不存在，或一个或两个R7可以存在且独立代表可选择取代的烷基或类似物）或类似物。）
• Novel condensed imidazole derivative
  申请人：Nakahira Hiroyuki

  公开号：US20070105890A1

  公开（公告）日：2007-05-10

  Disclosed is a compound represented by the formula (1) below which has a high DPP-IV inhibitory activity and is improved in safety, toxicity and the like. Also disclosed is a prodrug of such a compound and pharmaceutically acceptable salts of them. (In the formula, R 1 represents a hydrogen atom, an optionally substituted alkyl group or the like; R 2 and R 3 independently represent a hydrogen atom, an optionally substituted alkyl group or the like; R 4 and R 5 independently represent a hydrogen atom, an optionally substituted alkyl group or the like: R 6 represents a hydrogen atom, an optionally substituted aryl group or the like; and —Y—NH 2 , represents a group represented by the following formula (A): (wherein m is 0, 1 or 2; and R 7 may not exist or one or two R 7 may exist and independently represent an optionally substituted alkyl group or the like) or the like.]

  公开了一种化合物，其表示为以下式（1），具有较高的DPP-IV抑制活性并且在安全性、毒性等方面得到改善。还公开了这种化合物的前药和它们的药学上可接受的盐。（在该式中，R1表示氢原子，可选择性取代的烷基或类似物; R2和R3独立地表示氢原子，可选择性取代的烷基或类似物; R4和R5独立地表示氢原子，可选择性取代的烷基或类似物：R6表示氢原子，可选择性取代的芳基或类似物; 而—Y—NH2表示由以下式（A）表示的基团：（其中m为0、1或2；而R7可能不存在或一个或两个R7可能存在且独立地表示可选择性取代的烷基或类似物）或类似物。）
• 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.