tert-butyl 4-((2-(pyridin-4-yl)ethyl)carbamoyl)piperidine-1-carboxylate | 1401619-18-8

• 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: tert-butyl 4-((2-(pyridin-4-yl)ethyl)carbamoyl)piperidine-1-carboxylate
• 英文别名: tert-butyl 4-(2-pyridin-4-ylethylcarbamoyl)piperidine-1-carboxylate
• CAS: 1401619-18-8
• 化学式: C₁₈H₂₇N₃O₃
• 分子量: 333.431
• InChiKey: OVWDYQFZHSCIPG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  71.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-((2-(pyridin-4-yl)ethyl)carbamoyl)piperidine-1-carboxylate 在 盐酸 作用下， 以 1,4-二氧六环 、 乙醚 为溶剂， 反应 0.5h， 以97%的产率得到N-(2-(pyridin-4-yl)ethyl)piperidine-4-carboxamide dihydrochloride
  参考文献：
  名称：

  ARBOVIRUS INHIBITORS AND USES THEREOF

  摘要：

  本发明涉及化学化合物、其发现方法以及其治疗用途。具体而言，本发明提供了作为虫媒病毒抑制剂的化合物。

  公开号：

  US20120252807A1
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 21.0h， 生成 tert-butyl 4-((2-(pyridin-4-yl)ethyl)carbamoyl)piperidine-1-carboxylate
  参考文献：
  名称：

  Optimization of Novel Indole-2-carboxamide Inhibitors of Neurotropic Alphavirus Replication

  摘要：

  Neurotropic alphaviruses, which include western equine encephalitis virus (WEEV) and Fort Morgan virus, are mosquito-borne pathogens that infect the central nervous system causing acute and potentially fatal encephalitis. We previously reported a novel series of indole-2-carboxamides as alphavirus replication inhibitors, one of which conferred protection against neuroadapted Sindbis virus infection in mice. We describe here further development of this series, resulting in 10-fold improvement in potency in a WEEV repliton assay and up to 40-fold increases in half-lives in mouse liver microsomes. Using a rhodamine123 uptake assay in MDR1-MDCKII cells, we were able to identify structural modifications that markedly reduce recognition by P-glycoprotein, the key efflux transporter at the blood brain barrier. In a preliminary mouse PK study, we were able to demonstrate that two new analogues could achieve higher and/or longer plasma drug exposures than our previous lead and that one compound achieved measurable drug levels in the brain.

  DOI：

  10.1021/jm401330r

文献信息

• Arbovirus inhibitors and uses thereof
  申请人：Larsen Scott

  公开号：US08846684B2

  公开（公告）日：2014-09-30

  The present invention relates to chemical compounds, methods for their discovery, and their therapeutic use. In particular, the present invention provides compounds as inhibitors of arboviruses.

  本发明涉及化学化合物，其发现方法以及它们的治疗用途。特别是，本发明提供了作为蚊媒病毒抑制剂的化合物。
• US8846684B2
  申请人：——

  公开号：US8846684B2

  公开（公告）日：2014-09-30
• [EN] ARBOVIRUS INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS D'ARBOVIRUS ET LEURS UTILISATIONS
  申请人：UNIV MICHIGAN

  公开号：WO2012170098A2

  公开（公告）日：2012-12-13

  The present invention relates to chemical compounds, methods for their discovery, and their therapeutic use. In particular, the present invention provides compounds as inhibitors of arboviruses.
• Optimization of Novel Indole-2-carboxamide Inhibitors of Neurotropic Alphavirus Replication
  作者：Janice A. Sindac、Scott J. Barraza、Craig J. Dobry、Jianming Xiang、Pennelope K. Blakely、David N. Irani、Richard F. Keep、David J. Miller、Scott D. Larsen

  DOI：10.1021/jm401330r

  日期：2013.11.27

  Neurotropic alphaviruses, which include western equine encephalitis virus (WEEV) and Fort Morgan virus, are mosquito-borne pathogens that infect the central nervous system causing acute and potentially fatal encephalitis. We previously reported a novel series of indole-2-carboxamides as alphavirus replication inhibitors, one of which conferred protection against neuroadapted Sindbis virus infection in mice. We describe here further development of this series, resulting in 10-fold improvement in potency in a WEEV repliton assay and up to 40-fold increases in half-lives in mouse liver microsomes. Using a rhodamine123 uptake assay in MDR1-MDCKII cells, we were able to identify structural modifications that markedly reduce recognition by P-glycoprotein, the key efflux transporter at the blood brain barrier. In a preliminary mouse PK study, we were able to demonstrate that two new analogues could achieve higher and/or longer plasma drug exposures than our previous lead and that one compound achieved measurable drug levels in the brain.
• ARBOVIRUS INHIBITORS AND USES THEREOF
  申请人：Larsen Scott

  公开号：US20120252807A1

  公开（公告）日：2012-10-04

  The present invention relates to chemical compounds, methods for their discovery, and their therapeutic use. In particular, the present invention provides compounds as inhibitors of arboviruses.

  本发明涉及化学化合物、其发现方法以及其治疗用途。具体而言，本发明提供了作为虫媒病毒抑制剂的化合物。