4-{2-[1-methyl-4-(1-methyl-4-(1-methyl-4-(3-chloro-6-trifluorobenzo[b]thiophene-2-carboxamido)-2-pyrrolecarboxamido)-2-pyrrolecarboxamido)-2-pyrrolecarboxamido]ethyl}morpholine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻吩类
• 英文名称: 4-{2-[1-methyl-4-(1-methyl-4-(1-methyl-4-(3-chloro-6-trifluorobenzo[b]thiophene-2-carboxamido)-2-pyrrolecarboxamido)-2-pyrrolecarboxamido)-2-pyrrolecarboxamido]ethyl}morpholine
• 英文别名: 4-[[4-[[4-[[3-chloro-6-(trifluoromethyl)-1-benzothiophene-2-carbonyl]amino]-1-methylpyrrole-2-carbonyl]amino]-1-methylpyrrole-2-carbonyl]amino]-1-methyl-N-(2-morpholin-4-ylethyl)pyrrole-2-carboxamide
• 化学式: C₃₄H₃₄ClF₃N₈O₅S
• 分子量: 759.209
• InChiKey: ALKDHGIPMWOTIO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  52
• 可旋转键数：
  10
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  172
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  1-甲基-4-硝基-2-(三氟乙酰)-1H-吡咯 在 palladium on activated charcoal 盐酸 、 氢气 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 25.0~80.0 ℃ 、861.84 kPa 条件下， 反应 38.17h， 生成 4-{2-[1-methyl-4-(1-methyl-4-(1-methyl-4-(3-chloro-6-trifluorobenzo[b]thiophene-2-carboxamido)-2-pyrrolecarboxamido)-2-pyrrolecarboxamido)-2-pyrrolecarboxamido]ethyl}morpholine
  参考文献：
  名称：

  DNA Binding Ligands Targeting Drug-Resistant Bacteria:  Structure, Activity, and Pharmacology

  摘要：

  We describe the lead optimization and structure-activity relationship of DNA minor-groove binding ligands, a novel class of antibacterial molecules. These compounds have been shown to target A/T-rich sites within the bacterial genome and, as a result, inhibit DNA replication and RNA transcription. The optimization was focused on N-terminal aromatic heterocycles and C-terminal amines and resulted in compounds with improved in vivo tolerability and excellent in vitro antibacterial potency (MIC greater than or equal to 0.031 mug/mL) against a broad range of Grainpositive pathogens, including drug-resistant strains such as methicillin-resistant Stapylococcus aureus (MRSA), penicillin-resistant Streptococcus pneumoniae (PRSP), and vancomycin-resistant Enterococcus faecalis (VRE). In a first proof-of-concept study, a selected compound (35) showed in vivo efficacy in a mouse peritonitis model against methicillin-sensitive S. aureus infection with an ED50 value of 30 mg/kg.

  DOI：

  10.1021/jm030097a

文献信息

• DNA Binding Ligands Targeting Drug-Resistant Bacteria:  Structure, Activity, and Pharmacology
  作者：Jacob A. Kaizerman、Matthew I. Gross、Yigong Ge、Sarah White、Wenhao Hu、Jian-Xin Duan、Eldon E. Baird、Kirk W. Johnson、Richard D. Tanaka、Heinz E. Moser、Roland W. Bürli

  DOI：10.1021/jm030097a

  日期：2003.8.1

  We describe the lead optimization and structure-activity relationship of DNA minor-groove binding ligands, a novel class of antibacterial molecules. These compounds have been shown to target A/T-rich sites within the bacterial genome and, as a result, inhibit DNA replication and RNA transcription. The optimization was focused on N-terminal aromatic heterocycles and C-terminal amines and resulted in compounds with improved in vivo tolerability and excellent in vitro antibacterial potency (MIC greater than or equal to 0.031 mug/mL) against a broad range of Grainpositive pathogens, including drug-resistant strains such as methicillin-resistant Stapylococcus aureus (MRSA), penicillin-resistant Streptococcus pneumoniae (PRSP), and vancomycin-resistant Enterococcus faecalis (VRE). In a first proof-of-concept study, a selected compound (35) showed in vivo efficacy in a mouse peritonitis model against methicillin-sensitive S. aureus infection with an ED50 value of 30 mg/kg.