(Z)-2-((E)-1-(3-bromophenyl)-3-(3,4-dimethoxyphenyl)allylidene)hydrazinecarboximidamide

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: (Z)-2-((E)-1-(3-bromophenyl)-3-(3,4-dimethoxyphenyl)allylidene)hydrazinecarboximidamide
• 英文别名: 2-[(Z)-[(E)-1-(3-bromophenyl)-3-(3,4-dimethoxyphenyl)prop-2-enylidene]amino]guanidine
• 化学式: C₁₈H₁₉BrN₄O₂
• 分子量: 403.278
• InChiKey: BNEHKORFYRCBRM-KRDYMSEPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  95.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-(3-bromophenyl)-3-(3,4-dimethoxyphenyl)prop-2-en-1-one 、 肼甲酰亚胺酰胺一氯化氢 在 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 以37%的产率得到(Z)-2-((E)-1-(3-bromophenyl)-3-(3,4-dimethoxyphenyl)allylidene)hydrazinecarboximidamide
  参考文献：
  名称：

  Rational design, synthesis and in vitro evaluation of allylidene hydrazinecarboximidamide derivatives as BACE-1 inhibitors

  摘要：

  BACE-1 (beta-secretase) is considered to be one of the promising targets for treatment of Alzheimer's disease as it catalyzes the rate limiting step of A beta-42 production. Herein, we report a novel class of allylidene hydrazinecarboximidamide derivatives as moderately potent BACE-1 inhibitors, having aminoguanidine substitution on allyl linker with two aromatic groups on either side. A library of derivatives was designed based on the docking studies, synthesized and evaluated for BACE-1 inhibition in vitro. The designed ligands displayed interactions with the catalytic aspartate dyad through guanidinium functionality. Further, the aromatic rings placed on either side of the linker occupied S1 and S3 active site regions contributing to the activity. These ligands were also predicted to follow Lipinski rule and cross blood brain barrier. Compound 2.21, having high docking score, was found to be most active with IC50 of 6.423 mu M indicating good correlation with docking prediction. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.11.044

文献信息

• Rational design, synthesis and in vitro evaluation of allylidene hydrazinecarboximidamide derivatives as BACE-1 inhibitors
  作者：Priti Jain、Pankaj K. Wadhwa、Shilpa Rohilla、Hemant R. Jadhav

  DOI：10.1016/j.bmcl.2015.11.044

  日期：2016.1

  BACE-1 (beta-secretase) is considered to be one of the promising targets for treatment of Alzheimer's disease as it catalyzes the rate limiting step of A beta-42 production. Herein, we report a novel class of allylidene hydrazinecarboximidamide derivatives as moderately potent BACE-1 inhibitors, having aminoguanidine substitution on allyl linker with two aromatic groups on either side. A library of derivatives was designed based on the docking studies, synthesized and evaluated for BACE-1 inhibition in vitro. The designed ligands displayed interactions with the catalytic aspartate dyad through guanidinium functionality. Further, the aromatic rings placed on either side of the linker occupied S1 and S3 active site regions contributing to the activity. These ligands were also predicted to follow Lipinski rule and cross blood brain barrier. Compound 2.21, having high docking score, was found to be most active with IC50 of 6.423 mu M indicating good correlation with docking prediction. (C) 2015 Elsevier Ltd. All rights reserved.