N-(3-(cis-3,5-dimethylpiperidin-1-yl)propyl)-1-((2-(2,4-dimethylphenyl)-5-methyloxazol-4-yl)methyl)piperidine-4-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-(3-(cis-3,5-dimethylpiperidin-1-yl)propyl)-1-((2-(2,4-dimethylphenyl)-5-methyloxazol-4-yl)methyl)piperidine-4-carboxamide
• 英文别名: 1-[[2-(2,4-dimethylphenyl)-5-methyl-1,3-oxazol-4-yl]methyl]-N-[3-[(3S,5R)-3,5-dimethylpiperidin-1-yl]propyl]piperidine-4-carboxamide
• 化学式: C₂₉H₄₄N₄O₂
• 分子量: 480.694
• InChiKey: DQOMBZGDQNRBQJ-SZPZYZBQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.66
• 拓扑面积：
  61.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2,4-二甲基苯甲醛 在 盐酸 、 4-二甲氨基吡啶 、 1-羟基苯并三唑一水物 、 potassium hydroxide 、 N,N'-二异丙基碳二亚胺 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 溶剂黄146 、 1,2-二氯乙烷 为溶剂， 反应 48.5h， 生成 N-(3-(cis-3,5-dimethylpiperidin-1-yl)propyl)-1-((2-(2,4-dimethylphenyl)-5-methyloxazol-4-yl)methyl)piperidine-4-carboxamide
  参考文献：
  名称：

  Development of an Aryloxazole Class of Hepatitis C Virus Inhibitors Targeting the Entry Stage of the Viral Replication Cycle

  摘要：

  Reliance on hepatitis C virus (HCV) replicon systems and protein-based screening assays has led to treatments that target HCV viral replication proteins. The model does not encompass other viral replication cycle steps such as entry, processing, assembly and secretion, or viral host factors. We previously applied a phenotypic high-throughput screening platform based on an infectious HCV system and discovered an aryloxazole-based anti-HCV hit. Structure-activity relationship studies revealed several compounds exhibiting EC50 values below 100 nM. Lead compounds showed inhibition of the HCV pseudoparticle entry, suggesting a different mode of action from existing HCV drugs. Hit 7a and lead 7ii both showed synergistic effects in combination with existing HCV drugs. In vivo pharmacokinetics studies of Iii showed high liver distribution and long half-life without obvious hepatotoxicity. The lead compounds are promising as preclinical candidates for the treatment of HCV infection and as molecular probes to study HCV pathogenesis.

  DOI：

  10.1021/acs.jmedchem.7b00561

文献信息

• [EN] HETEROCYCLIC COMPOUNDS AND METHODS OF USE THEREOF<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES ET LEURS MÉTHODES D'UTILISATION
  申请人：US HEALTH

  公开号：WO2015192077A1

  公开（公告）日：2015-12-17

  Disclosed are compounds of formula (I), formula (II), and formula (III): wherein Ar, R1, A, and X are as defined in the specification. These compounds are antiviral agents and are contemplated for use in the treatment of viral infections, for example, hepatitis C. These compounds are also contemplated for use in treating or preventing cancers.

  公开的是以下化合物的结构：式(I)、式(II)和式(III)，其中Ar、R1、A和X的定义如规范中所述。这些化合物是抗病毒剂，可用于治疗病毒感染，例如丙型肝炎。这些化合物也可用于治疗或预防癌症。
• Heterocyclic compounds and methods of use thereof
  申请人：The United States of America, as represented by the Secretary, Department of Health and Human Services

  公开号：US10202367B2

  公开（公告）日：2019-02-12

  Disclosed are compounds of formula (I), formula (II), and formula (III): wherein Ar, R1, A, and X are as defined in the specification. These compounds are antiviral agents and are contemplated for use in the treatment of viral infections, for example, hepatitis C. These compounds are also contemplated for use in treating or preventing cancers.

  公开了式(I)、式(II)和式(III)化合物：其中 Ar、R1、A 和 X 如说明书中所定义。这些化合物是抗病毒剂，可用于治疗病毒感染，例如丙型肝炎。
• HETEROCYCLIC COMPOUNDS AND METHODS OF USE THEREOF
  申请人：The U.S.A. as represented by the Secretary, Department of Health and Human Services

  公开号：EP3154966B1

  公开（公告）日：2019-05-08
• Development of an Aryloxazole Class of Hepatitis C Virus Inhibitors Targeting the Entry Stage of the Viral Replication Cycle
  作者：Shanshan He、Kelin Li、Billy Lin、Zongyi Hu、Jingbo Xiao、Xin Hu、Amy Q. Wang、Xin Xu、Marc Ferrer、Noel Southall、Wei Zheng、Jeffrey Aubé、Frank J. Schoenen、Juan J. Marugan、T. Jake Liang、Kevin J. Frankowski

  DOI：10.1021/acs.jmedchem.7b00561

  日期：2017.7.27

  Reliance on hepatitis C virus (HCV) replicon systems and protein-based screening assays has led to treatments that target HCV viral replication proteins. The model does not encompass other viral replication cycle steps such as entry, processing, assembly and secretion, or viral host factors. We previously applied a phenotypic high-throughput screening platform based on an infectious HCV system and discovered an aryloxazole-based anti-HCV hit. Structure-activity relationship studies revealed several compounds exhibiting EC50 values below 100 nM. Lead compounds showed inhibition of the HCV pseudoparticle entry, suggesting a different mode of action from existing HCV drugs. Hit 7a and lead 7ii both showed synergistic effects in combination with existing HCV drugs. In vivo pharmacokinetics studies of Iii showed high liver distribution and long half-life without obvious hepatotoxicity. The lead compounds are promising as preclinical candidates for the treatment of HCV infection and as molecular probes to study HCV pathogenesis.