1-(3-(benzyloxy)pyridin-2-yl)-3-(tert-butyl)urea

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(3-(benzyloxy)pyridin-2-yl)-3-(tert-butyl)urea
• 英文别名: 1-Tert-butyl-3-(3-phenylmethoxypyridin-2-yl)urea；1-tert-butyl-3-(3-phenylmethoxypyridin-2-yl)urea
• 化学式: C₁₇H₂₁N₃O₂
• 分子量: 299.373
• InChiKey: AQZADHLLCRISGP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  63.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  溴甲苯 在 四丁基溴化铵 、 sodium hydride 、 sodium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 mineral oil 为溶剂， 反应 18.25h， 生成 1-(3-(benzyloxy)pyridin-2-yl)-3-(tert-butyl)urea
  参考文献：
  名称：

  Discovery of 1-(3-(benzyloxy)pyridin-2-yl)-3-(2-(piperazin-1-yl)ethyl)urea: A new modulator for amyloid beta-induced mitochondrial dysfunction

  摘要：

  Herein, we report a new series of aliphatic substituted pyridyl-urea small molecules synthesized as potential modulators for amyloid beta (A beta) induced mitochondrial dysfunction. Their blocking activities against A beta-induced mitochondrial permeability transition pore (mPTP) opening were evaluated by JC-1 assay which measures the change of mitochondrial membrane potential (Delta Psi m). The inhibitory activity of sixteen compounds against A beta-induced mPTP opening was superior or almost similar to that of the standard Cyclosporin A (CsA). Among them, 1-(3-(benzyloxy) pyridin-2-yl)-3-(2-(piperazin-1-yl)ethyl)urea (5x) effectively maintained mitochondrial function and cell viabilities on ATP assay, MTT assay, and ROS assay. Using CDocker algorithm, a molecular docking model presented a plausible binding mode for 5x with cyclophilin D (CypD) receptor as a major component of mPTP. Moreover, hERG and BBB-PAMPA assays presented safe cardiotoxicity and high CNS bioavailability profiles for 5x. Taken as a whole, this report presents compound 5x as a new nonpeptidyl mPTP blocker may hold a promise for further development of Alzheimer's disease (AD) therapeutics. (C) 2016 Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2016.12.057

文献信息

• Discovery of 1-(3-(benzyloxy)pyridin-2-yl)-3-(2-(piperazin-1-yl)ethyl)urea: A new modulator for amyloid beta-induced mitochondrial dysfunction
  作者：Ahmed Elkamhawy、Jung-eun Park、Ahmed H.E. Hassan、Hyunhwa Ra、Ae Nim Pae、Jiyoun Lee、Beoung-Geon Park、Bongjin Moon、Hyun-Mee Park、Eun Joo Roh

  DOI：10.1016/j.ejmech.2016.12.057

  日期：2017.3

  Herein, we report a new series of aliphatic substituted pyridyl-urea small molecules synthesized as potential modulators for amyloid beta (A beta) induced mitochondrial dysfunction. Their blocking activities against A beta-induced mitochondrial permeability transition pore (mPTP) opening were evaluated by JC-1 assay which measures the change of mitochondrial membrane potential (Delta Psi m). The inhibitory activity of sixteen compounds against A beta-induced mPTP opening was superior or almost similar to that of the standard Cyclosporin A (CsA). Among them, 1-(3-(benzyloxy) pyridin-2-yl)-3-(2-(piperazin-1-yl)ethyl)urea (5x) effectively maintained mitochondrial function and cell viabilities on ATP assay, MTT assay, and ROS assay. Using CDocker algorithm, a molecular docking model presented a plausible binding mode for 5x with cyclophilin D (CypD) receptor as a major component of mPTP. Moreover, hERG and BBB-PAMPA assays presented safe cardiotoxicity and high CNS bioavailability profiles for 5x. Taken as a whole, this report presents compound 5x as a new nonpeptidyl mPTP blocker may hold a promise for further development of Alzheimer's disease (AD) therapeutics. (C) 2016 Published by Elsevier Masson SAS.