N-[2-(4-chlorophenyl)ethyl]-4-(piperidin-1-ylmethyl)benzamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: N-[2-(4-chlorophenyl)ethyl]-4-(piperidin-1-ylmethyl)benzamide
• 化学式: C₂₁H₂₅ClN₂O
• 分子量: 356.895
• InChiKey: VHOHDFNYSIPXHV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  4-(1-哌啶基甲基)苯甲酸甲酯 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 生成 N-[2-(4-chlorophenyl)ethyl]-4-(piperidin-1-ylmethyl)benzamide
  参考文献：
  名称：

  Discovery of a Benzamide Derivative That Protects Pancreatic β-Cells against Endoplasmic Reticulum Stress

  摘要：

  Endoplasmic reticulum (ER) stress-mediated pancreatic insulin-producing beta-cell dysfunction and death are critical elements in the onset and progression of both type 1 and type 2 diabetes. Here, through cell-based high throughput screening we identified benzamide derivatives as a novel class of beta-cell protective agents against ER stress-induced dysfunction and death. Through structure activity relationship optimization, a 3-(N-piperidinyl)methylbenzamide derivative 13d markedly protects beta-cells against ER stress-induced dysfunction and death with near 100% maximum rescue activity and an EC50 of 0.032 mu M. Compound 13d alleviates ER stress in beta-cells by suppressing ER stress-mediated activation of all three branches of unfolded protein response (UPR) and apoptotic genes. Finally, we show that 13d significantly lowers blood glucose levels and increases concomitant beta-cell survival and number in a streptozotocin-induced diabetic mouse model. Identification of beta-cell-protective small molecules against ER stress provides a new promising modality for the treatment of diabetes.

  DOI：

  10.1021/acs.jmedchem.7b00435

文献信息

• [EN] BENZAMIDE DERIVATIVES FOR INHIBITING ENDOPLASMIC RETICULUM (ER) STRESS<br/>[FR] DÉRIVÉS DE BENZAMIDE PERMETTANT D'INHIBER LE STRESS DU RÉTICULUM ENDOPLASMIQUE (ER)
  申请人：UNIV OKLAHOMA

  公开号：WO2018232264A1

  公开（公告）日：2018-12-20

  Novel 3-(N-piperidinyl)methyl benzamide derivatives are disclosed. The compounds can be used in treating diseases and conditions which are associated with abnormal cell function related to endoplasmic reticulum (ER) stress. For example, the compounds can be used as suppressors of ER stress-induced pancreatic β-cell dysfunction and death, for example in the treatment of diabetes.

  披露了新型3-(N-哌啶基)甲基苯甲酰胺衍生物。这些化合物可用于治疗与内质网（ER）应激相关的异常细胞功能引起的疾病和症状。例如，这些化合物可用作抑制ER应激诱导的胰岛素β细胞功能障碍和死亡的药物，例如用于治疗糖尿病。
• Discovery of a Benzamide Derivative That Protects Pancreatic β-Cells against Endoplasmic Reticulum Stress
  作者：Hongliang Duan、Yu Li、Daleep Arora、Depeng Xu、Hui-Ying Lim、Weidong Wang

  DOI：10.1021/acs.jmedchem.7b00435

  日期：2017.7.27

  Endoplasmic reticulum (ER) stress-mediated pancreatic insulin-producing beta-cell dysfunction and death are critical elements in the onset and progression of both type 1 and type 2 diabetes. Here, through cell-based high throughput screening we identified benzamide derivatives as a novel class of beta-cell protective agents against ER stress-induced dysfunction and death. Through structure activity relationship optimization, a 3-(N-piperidinyl)methylbenzamide derivative 13d markedly protects beta-cells against ER stress-induced dysfunction and death with near 100% maximum rescue activity and an EC50 of 0.032 mu M. Compound 13d alleviates ER stress in beta-cells by suppressing ER stress-mediated activation of all three branches of unfolded protein response (UPR) and apoptotic genes. Finally, we show that 13d significantly lowers blood glucose levels and increases concomitant beta-cell survival and number in a streptozotocin-induced diabetic mouse model. Identification of beta-cell-protective small molecules against ER stress provides a new promising modality for the treatment of diabetes.