3-Chloro-6-cyclopropyl-8-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carbonyl chloride | 1284246-41-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并吡啶类
• 英文名称: 3-Chloro-6-cyclopropyl-8-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carbonyl chloride
• 英文别名: 3-chloro-6-cyclopropyl-8-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carbonyl chloride
• CAS: 1284246-41-8
• 化学式: C₁₂H₇Cl₂F₃N₂O
• 分子量: 323.102
• InChiKey: UCMQLUKMPNGUDD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  34.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-Chloro-6-cyclopropyl-8-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carbonyl chloride 、 1-cyclobutyl-2-piperazinone trifluoroacetate 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 4-{[3-chloro-6-cyclopropyl-8-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl]carbonyl}-1-cyclobutyl-2-piperazinone
  参考文献：
  名称：

  [EN] PIPERAZINYL ANTIVIRAL AGENTS
  [FR] AGENTS ANTI-VIRAUX À BASE DE PIPÉRAZINYLE

  摘要：

  公开号：

  WO2011041713A3
• 作为产物：
  描述：

  3-chloro-6-cyclopropyl-8-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxylic acid 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 生成 3-Chloro-6-cyclopropyl-8-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carbonyl chloride
  参考文献：
  名称：

  [EN] PIPERAZINYL ANTIVIRAL AGENTS
  [FR] AGENTS ANTI-VIRAUX À BASE DE PIPÉRAZINYLE

  摘要：

  公开号：

  WO2011041713A3

文献信息

• Hepatitis C Replication Inhibitors That Target the Viral NS4B Protein
  作者：John F. Miller、Pek Y. Chong、J. Brad Shotwell、John G. Catalano、Vincent W.-F. Tai、Jing Fang、Anna L. Banka、Christopher D. Roberts、Michael Youngman、Huichang Zhang、Zhiping Xiong、Amanda Mathis、Jeffery J. Pouliot、Robert K. Hamatake、Daniel J. Price、John W. Seal、Lisa L. Stroup、Katrina L. Creech、Luz H. Carballo、Dan Todd、Andrew Spaltenstein、Sylvia Furst、Zhi Hong、Andrew J. Peat

  DOI：10.1021/jm400125h

  日期：2014.3.13

  We describe the preclinical development and in vivo efficacy of a novel chemical series that inhibits hepatitis C virus replication via direct interaction with the viral nonstructural protein 4B (NS4B). Significant potency improvements were realized through isosteric modifications to our initial lead la. The temptation to improve antiviral activity while compromising physicochemical properties was tempered by the judicial use of ligand efficiency indices during lead optimization. In this manner, compound la was transformed into (+)-28a which possessed an improved antiviral profile with no increase in molecular weight and only a modest elevation in lipophilicity. Additionally, we employed a chimeric "humanized" mouse model of HCV infection to demonstrate for the first time that a small molecule with high in vitro affinity for NS4B can inhibit viral replication in vivo. This successful proof-of-concept study suggests that drugs targeting NS4B may represent a viable treatment option for curing HCV infection.
• [EN] PIPERAZINYL ANTIVIRAL AGENTS<br/>[FR] AGENTS ANTI-VIRAUX À BASE DE PIPÉRAZINYLE
  申请人：GLAXOSMITHKLINE LLC

  公开号：WO2011041713A3

  公开（公告）日：2012-04-05