1-(4-(benzylamino)-1-isopropyl-1H-benzo[d]imidazol-6-yloxy)butan-2-ol | 1262957-23-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 1-(4-(benzylamino)-1-isopropyl-1H-benzo[d]imidazol-6-yloxy)butan-2-ol
• 英文别名: 1-[7-(benzylamino)-3-propan-2-ylbenzimidazol-5-yl]oxybutan-2-ol
• CAS: 1262957-23-2
• 化学式: C₂₁H₂₇N₃O₂
• 分子量: 353.464
• InChiKey: LWIHHDQTVXWNDB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  59.3
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-((4-(benzylamino)-1-isopropyl-1H-benzo[d]imidazol-6-yl)oxy)butan-2-yl benzoate 在 甲醇 、 potassium hydroxide 作用下， 反应 12.0h， 以56%的产率得到1-(4-(benzylamino)-1-isopropyl-1H-benzo[d]imidazol-6-yloxy)butan-2-ol
  参考文献：
  名称：

  Design, synthesis, and testing of an 6-O-linked series of benzimidazole based inhibitors of CDK5/p25

  摘要：

  Alzheimer's disease (AD) is a progressive neurodegenerative disease resulting in cognitive and behavioral impairment. The two classic pathological hallmarks of AD include extraneuronal deposition of amyloid beta (A beta) and intraneuronal formation of neurofibrillary tangles (NFTs). NFTs contain hyperphosphorylated tau. Tau is the major microtubule-associated protein in neurons and stabilizes microtubules (MTs). Cyclin dependent kinase 5 (CDK5), when activated by the regulatory binding protein p25, phosphorylates tau at a number of proline-directed serine/threonine residues, resulting in formation of phosphorylated tau as paired helical filaments (PHFs) then in subsequent deposition of PHFs as NFTs. Beginning with the structure of Roscovitine, a moderately selective CDK5 inhibitor, we sought to conduct structural modifications to increase inhibitory potency of CDK5 and increase selectivity over a similar enzyme, cyclin dependent kinase 2 (CDK2). The design, synthesis, and testing of a series of 1-isopropyl-4-aminobenzyl-6-ether-linked benzimidazoles is presented. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.11.022

文献信息

• Design, synthesis, and testing of an 6-O-linked series of benzimidazole based inhibitors of CDK5/p25
  作者：Prashi Jain、Patrick T. Flaherty、Shuyan Yi、Ishveen Chopra、Gwenyth Bleasdell、Josh Lipay、Yoan Ferandin、Laurent Meijer、Jeffry D. Madura

  DOI：10.1016/j.bmc.2010.11.022

  日期：2011.1

  Alzheimer's disease (AD) is a progressive neurodegenerative disease resulting in cognitive and behavioral impairment. The two classic pathological hallmarks of AD include extraneuronal deposition of amyloid beta (A beta) and intraneuronal formation of neurofibrillary tangles (NFTs). NFTs contain hyperphosphorylated tau. Tau is the major microtubule-associated protein in neurons and stabilizes microtubules (MTs). Cyclin dependent kinase 5 (CDK5), when activated by the regulatory binding protein p25, phosphorylates tau at a number of proline-directed serine/threonine residues, resulting in formation of phosphorylated tau as paired helical filaments (PHFs) then in subsequent deposition of PHFs as NFTs. Beginning with the structure of Roscovitine, a moderately selective CDK5 inhibitor, we sought to conduct structural modifications to increase inhibitory potency of CDK5 and increase selectivity over a similar enzyme, cyclin dependent kinase 2 (CDK2). The design, synthesis, and testing of a series of 1-isopropyl-4-aminobenzyl-6-ether-linked benzimidazoles is presented. (C) 2010 Elsevier Ltd. All rights reserved.