1-(1-(4-chlorobenzyl)-1H-pyrrole-2-carbonyl)piperidine-4-carboxylic acid | 1401619-14-4

• 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: 1-(1-(4-chlorobenzyl)-1H-pyrrole-2-carbonyl)piperidine-4-carboxylic acid
• 英文别名: 1-[1-[(4-chlorophenyl)methyl]pyrrole-2-carbonyl]piperidine-4-carboxylic acid
• CAS: 1401619-14-4
• 化学式: C₁₈H₁₉ClN₂O₃
• 分子量: 346.813
• InChiKey: CHIRZPUUTFZVAL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  62.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(2-氨基乙基)吡啶 、 1-(1-(4-chlorobenzyl)-1H-pyrrole-2-carbonyl)piperidine-4-carboxylic acid 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 作用下， 以 二氯甲烷 为溶剂， 反应 18.5h， 以75%的产率得到1-(1-(4-chlorobenzyl)-1H-pyrrole-2-carbonyl)-N-(2-(pyridin-4-yl)ethyl)piperidine-4-carboxamide
  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
• 作为产物：
  描述：

  4-氯氯苄 在 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 sodium hydroxide 、 lithium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 168.5h， 生成 1-(1-(4-chlorobenzyl)-1H-pyrrole-2-carbonyl)piperidine-4-carboxylic acid
  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：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。
• 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.