cis-4-amino-5-chloro-N-[1-(2-(1H-pyrrol-1-yl)ethyl)-3-methoxypiperidin-4-yl]-2-methoxybenzamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: cis-4-amino-5-chloro-N-[1-(2-(1H-pyrrol-1-yl)ethyl)-3-methoxypiperidin-4-yl]-2-methoxybenzamide
• 英文别名: cis-4-amino-5-chloro-N-(1-(2-(1H-pyrrol-1-yl)ethyl)-3-methoxy-piperidin-4-yl)-2-methoxy-benzamide；4-amino-5-chloro-2-methoxy-N-[3-methoxy-1-(2-pyrrol-1-ylethyl)piperidin-4-yl]benzamide
• 化学式: C₂₀H₂₇ClN₄O₃
• 分子量: 406.912
• InChiKey: BESRCGRINPRVRC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  81.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3,4,4-三甲氧基哌啶-1-羧酸乙酯 在 硫酸 、 ammonium acetate 、 sodium cyanoborohydride 、 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 potassium iodide 、 potassium hydroxide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 29.25h， 生成 cis-4-amino-5-chloro-N-[1-(2-(1H-pyrrol-1-yl)ethyl)-3-methoxypiperidin-4-yl]-2-methoxybenzamide
  参考文献：
  名称：

  Discovery and SAR of N-(1-((substituted piperidin-4-yl)methyl)-3-methoxypiperidin-4-yl)-2-methoxybenzamide derivatives: 5-Hydroxytryptamine receptor 4 agonist as a potent prokinetic agent

  摘要：

  A series of novel benzamide derivatives, altering the 4-fluorophenylalkyl moiety in cisapride, were synthesized as 5-HT4 receptor agonists, and SAR of these analogs was examined on in vitro and in vivo prokinetic activities. These compounds were synthesized for high 5-HT4 receptor binding affinities and low hERG affinities. Several types of analogs were obtained and screened for 5-HT4 binding, hERG blocking, agonism, and gastric emptying assessment. Among the analogues, compound 23g showed promising results compared with the other analogs with respect to gastric emptying rates in rats. Therefore, we suggest that it may be a clinical candidate for the development of a potent prokinetic agent to treat GI disorders. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.12.006

文献信息

• NOVEL BENZAMIDE DERIVATIVES AND PROCESS FOR THE PREPARTION THEREOF
  申请人：Yoo Moo-Hi

  公开号：US20100105727A1

  公开（公告）日：2010-04-29

  The present invention provides a novel benzamide derivative represented by formula 1 and an isomer, a pharmaceutically acceptable salt or hydrate thereof, and a composition for activating a 5-HT4 receptor comprising the same, as an active ingredient. Benzamide derivatives of the present invention has superior affinity for 5-HT4 receptors, capability to reduce the gastric evacuation time, capability to alleviate ventricular tachycardia, ventricular fibrillation, torsades de pointes and QT prolongation, and low toxicity. Therefore, benzamide derivatives of the present invention are therapeutically effective for digestive system diseases.

  本发明提供了一种新颖的苯甲酰胺衍生物，其由式1表示，以及一个异构体，其药学上可接受的盐或水合物，以及包含相同物质的用于激活5-HT4受体的组合物，作为活性成分。本发明的苯甲酰胺衍生物具有优越的亲和力，能够减少胃排空时间，能够缓解室性心动过速、室颤、扭转型室性心动过速和QT间期延长，并且毒性低。因此，本发明的苯甲酰胺衍生物在治疗消化系统疾病方面具有治疗效果。
• Discovery and SAR of N-(1-((substituted piperidin-4-yl)methyl)-3-methoxypiperidin-4-yl)-2-methoxybenzamide derivatives: 5-Hydroxytryptamine receptor 4 agonist as a potent prokinetic agent
  作者：Jung Sang Park、Weonbin Im、Sunghak Choi、Sook Jin Park、Jun Min Jung、Ki Seon Baek、Han Pyo Son、Satyasheel Sharma、In Su Kim、Young Hoon Jung

  DOI：10.1016/j.ejmech.2015.12.006

  日期：2016.2

  A series of novel benzamide derivatives, altering the 4-fluorophenylalkyl moiety in cisapride, were synthesized as 5-HT4 receptor agonists, and SAR of these analogs was examined on in vitro and in vivo prokinetic activities. These compounds were synthesized for high 5-HT4 receptor binding affinities and low hERG affinities. Several types of analogs were obtained and screened for 5-HT4 binding, hERG blocking, agonism, and gastric emptying assessment. Among the analogues, compound 23g showed promising results compared with the other analogs with respect to gastric emptying rates in rats. Therefore, we suggest that it may be a clinical candidate for the development of a potent prokinetic agent to treat GI disorders. (C) 2015 Elsevier Masson SAS. All rights reserved.