phenyl 4-(pyridin-2-yl)piperazine-1-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: phenyl 4-(pyridin-2-yl)piperazine-1-carboxylate
• 英文别名: Phenyl 4-pyridin-2-ylpiperazine-1-carboxylate
• 化学式: C₁₆H₁₇N₃O₂
• 分子量: 283.33
• InChiKey: OOTVJRSIROMSLE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  45.7
• 氢给体数：
  0
• 氢受体数：
  4

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  1-(2-吡啶基)哌嗪	1-(2-pyridyl)piperazine	34803-66-2	C9H13N3	163.222

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	4-(pyridin-2-yl)piperazine-1-carbohydrazide	——	C10H15N5O	221.262

反应信息

• 作为反应物：
  描述：

  phenyl 4-(pyridin-2-yl)piperazine-1-carboxylate 在 hydrazine hydrate 作用下， 以 乙醇 为溶剂， 以84%的产率得到4-(pyridin-2-yl)piperazine-1-carbohydrazide
  参考文献：
  名称：

  Design and development of molecular hybrids of 2-pyridylpiperazine and 5-phenyl-1,3,4-oxadiazoles as potential multifunctional agents to treat Alzheimer's disease

  摘要：

  The diverse nature of Alzheimer's disease (AD) has prompted researchers to develop multi-functional agents. Herein, we have designed and synthesized molecular hybrids of 2-pyridylpiperazine and 5-phenyl-1,3,4-oxadiazoles. Biological activities of synthesized compounds suggested significant and balanced inhibitory potential against target enzymes. In particular, compound 49 containing 2,4-difluoro substitution at terminal phenyl ring considered as most potential lead with inhibition of acetylcholinesterase (hAChE, IC50 = 0.054 mu M), butyrylcholinesterase (hBChE, IC50 = 0.787 mu M) and beta-secretase-1 (hBACE-1, IC50 = 0.098 mu M). The enzyme kinetics study of 49 against hAChE suggested a mixed type of inhibition (Ki = 0.030 mu M). Also, 48 and 49 showed significant displacement of propidium iodide from the peripheral anionic site (PAS) of hAChE, excellent blood-brain barrier (BBB) permeability in parallel artificial membrane permeation assay (PAMPA), and neuroprotective ability against SH-SY5Y neuroblastoma cell lines. Further, 49 also exhibited anti-A beta aggregation activity in self- and AChE-induced thiofiavin T assay, which was ascertained by morphological characterization by atomic force microscopy (AFM). Moreover, in vivo behavioral studies signified learning and memory improvement by compound 49 in scopolamine- and A beta-induced cognitive dysfunctions performed on Y-maze and Morris water maze. The ex vivo studies suggested decreased AChE activity and antioxidant potential of compound 49, with good oral absorption characteristics ascertained by pharmacokinetic studies. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.111707
• 作为产物：
  描述：

  1-(2-吡啶基)哌嗪 、 氯甲酸苯酯 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以88%的产率得到phenyl 4-(pyridin-2-yl)piperazine-1-carboxylate
  参考文献：
  名称：

  Design and development of molecular hybrids of 2-pyridylpiperazine and 5-phenyl-1,3,4-oxadiazoles as potential multifunctional agents to treat Alzheimer's disease

  摘要：

  The diverse nature of Alzheimer's disease (AD) has prompted researchers to develop multi-functional agents. Herein, we have designed and synthesized molecular hybrids of 2-pyridylpiperazine and 5-phenyl-1,3,4-oxadiazoles. Biological activities of synthesized compounds suggested significant and balanced inhibitory potential against target enzymes. In particular, compound 49 containing 2,4-difluoro substitution at terminal phenyl ring considered as most potential lead with inhibition of acetylcholinesterase (hAChE, IC50 = 0.054 mu M), butyrylcholinesterase (hBChE, IC50 = 0.787 mu M) and beta-secretase-1 (hBACE-1, IC50 = 0.098 mu M). The enzyme kinetics study of 49 against hAChE suggested a mixed type of inhibition (Ki = 0.030 mu M). Also, 48 and 49 showed significant displacement of propidium iodide from the peripheral anionic site (PAS) of hAChE, excellent blood-brain barrier (BBB) permeability in parallel artificial membrane permeation assay (PAMPA), and neuroprotective ability against SH-SY5Y neuroblastoma cell lines. Further, 49 also exhibited anti-A beta aggregation activity in self- and AChE-induced thiofiavin T assay, which was ascertained by morphological characterization by atomic force microscopy (AFM). Moreover, in vivo behavioral studies signified learning and memory improvement by compound 49 in scopolamine- and A beta-induced cognitive dysfunctions performed on Y-maze and Morris water maze. The ex vivo studies suggested decreased AChE activity and antioxidant potential of compound 49, with good oral absorption characteristics ascertained by pharmacokinetic studies. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.111707

文献信息

• Design and development of molecular hybrids of 2-pyridylpiperazine and 5-phenyl-1,3,4-oxadiazoles as potential multifunctional agents to treat Alzheimer's disease
  作者：Avanish Tripathi、Priyanka Kumari Choubey、Piyoosh Sharma、Ankit Seth、Prabhash Nath Tripathi、Manish Kumar Tripathi、Santosh Kumar Prajapati、Sairam Krishnamurthy、Sushant Kumar Shrivastava

  DOI：10.1016/j.ejmech.2019.111707

  日期：2019.12

  The diverse nature of Alzheimer's disease (AD) has prompted researchers to develop multi-functional agents. Herein, we have designed and synthesized molecular hybrids of 2-pyridylpiperazine and 5-phenyl-1,3,4-oxadiazoles. Biological activities of synthesized compounds suggested significant and balanced inhibitory potential against target enzymes. In particular, compound 49 containing 2,4-difluoro substitution at terminal phenyl ring considered as most potential lead with inhibition of acetylcholinesterase (hAChE, IC50 = 0.054 mu M), butyrylcholinesterase (hBChE, IC50 = 0.787 mu M) and beta-secretase-1 (hBACE-1, IC50 = 0.098 mu M). The enzyme kinetics study of 49 against hAChE suggested a mixed type of inhibition (Ki = 0.030 mu M). Also, 48 and 49 showed significant displacement of propidium iodide from the peripheral anionic site (PAS) of hAChE, excellent blood-brain barrier (BBB) permeability in parallel artificial membrane permeation assay (PAMPA), and neuroprotective ability against SH-SY5Y neuroblastoma cell lines. Further, 49 also exhibited anti-A beta aggregation activity in self- and AChE-induced thiofiavin T assay, which was ascertained by morphological characterization by atomic force microscopy (AFM). Moreover, in vivo behavioral studies signified learning and memory improvement by compound 49 in scopolamine- and A beta-induced cognitive dysfunctions performed on Y-maze and Morris water maze. The ex vivo studies suggested decreased AChE activity and antioxidant potential of compound 49, with good oral absorption characteristics ascertained by pharmacokinetic studies. (C) 2019 Elsevier Masson SAS. All rights reserved.