1-(1-(4-chlorobenzyl)-1H-indole-2-carbonyl)piperidine-4-carboxylic acid | 1369487-49-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 1-(1-(4-chlorobenzyl)-1H-indole-2-carbonyl)piperidine-4-carboxylic acid
• 英文别名: 1-[1-[(4-chlorophenyl)methyl]indole-2-carbonyl]piperidine-4-carboxylic acid
• CAS: 1369487-49-9
• 化学式: C₂₂H₂₁ClN₂O₃
• 分子量: 396.873
• InChiKey: DXNPVEAZMWVTQT-UHFFFAOYSA-N

物化性质

• 沸点：
  652.1±55.0 °C(Predicted)
• 密度：
  1.34±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 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：

  3-氨甲基吡啶 、 1-(1-(4-chlorobenzyl)-1H-indole-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 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.17h， 生成 1-(1-(4-chlorobenzyl)-1H-indole-2-carbonyl)-N-(pyridin-3-ylmethyl)piperidine-4-carboxamide
  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：

  ethyl 1-(4-chlorobenzyl)-1H-indole-2-carboxylate 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 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 24.33h， 生成 1-(1-(4-chlorobenzyl)-1H-indole-2-carbonyl)piperidine-4-carboxylic acid
  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

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。
• 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.
• Novel Inhibitors of Neurotropic Alphavirus Replication That Improve Host Survival in a Mouse Model of Acute Viral Encephalitis
  作者：Janice A. Sindac、Bryan D. Yestrepsky、Scott J. Barraza、Kyle L. Bolduc、Pennelope K. Blakely、Richard F. Keep、David N. Irani、David J. Miller、Scott D. Larsen

  DOI：10.1021/jm300214e

  日期：2012.4.12

  Arboviral encephalitis is a potentially devastating human disease with no approved therapies that target virus replication. We previously discovered a novel class of thieno[3,2-b]pyrrole-based inhibitors active against neurotropic alphaviruses such as western equine encephalitis virus (WEEV) in cultured cells. In this report, we describe initial development of these novel antiviral compounds, including bioisosteric replacement of the 4H-thieno[3,2-b]pyrrole core with indole to improve metabolic stability and the introduction of chirality to assess target enantioselectivity. Selected modifications enhanced antiviral activity while maintaining low cytotoidcity, increased stability to microsomal metabolism, and also revealed striking enantiospecific activity in cultured cells. Furthermore, we demonstrate improved outcomes (both symptoms and survival) following treatment with indole analogue 9h (CCG-203926) in an in vivo mouse model of alphaviral encephalitis that closely correlate with the enantiospecific in vitro antiviral activity. These results represent a substantial advancement in the early preclinical development of a promising class of novel antiviral drugs against virulent neurotropic alphaviruses.
• Synthesis and biological activity of conformationally restricted indole-based inhibitors of neurotropic alphavirus replication: Generation of a three-dimensional pharmacophore
  作者：Scott J. Barraza、Janice A. Sindac、Craig J. Dobry、Philip C. Delekta、Pil H. Lee、David J. Miller、Scott D. Larsen

  DOI：10.1016/j.bmcl.2021.128171

  日期：2021.8
• US8846684B2
  申请人：——

  公开号：US8846684B2

  公开（公告）日：2014-09-30