1-methyl-4-{1-methyl-4-[1-methyl-4-(3-chlorothiophene-2-carboxamido)-2-pyrrolecarboxamido]-2-pyrrolecarboxamido}-2-pyrrolecarboxylic acid | 605658-33-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: 1-methyl-4-{1-methyl-4-[1-methyl-4-(3-chlorothiophene-2-carboxamido)-2-pyrrolecarboxamido]-2-pyrrolecarboxamido}-2-pyrrolecarboxylic acid
• 英文别名: 4-[[4-[[4-[(3-Chlorothiophene-2-carbonyl)amino]-1-methylpyrrole-2-carbonyl]amino]-1-methylpyrrole-2-carbonyl]amino]-1-methylpyrrole-2-carboxylic acid
• CAS: 605658-33-1
• 化学式: C₂₃H₂₁ClN₆O₅S
• 分子量: 528.976
• InChiKey: CEBXQYFPMYCBBC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  36
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  168
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-(3-氨丙基)吗啉 、 1-methyl-4-{1-methyl-4-[1-methyl-4-(3-chlorothiophene-2-carboxamido)-2-pyrrolecarboxamido]-2-pyrrolecarboxamido}-2-pyrrolecarboxylic acid 在 双(2-氧代-3-恶唑烷基)次磷酰氯 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 4-[[4-[[4-[(3-chlorothiophene-2-carbonyl)amino]-1-methylpyrrole-2-carbonyl]amino]-1-methylpyrrole-2-carbonyl]amino]-1-methyl-N-(3-morpholin-4-ylpropyl)pyrrole-2-carboxamide
  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
• 作为产物：
  描述：

  3-氯噻吩-2-羧酸 在 氢氧化钾 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N-甲基吡咯烷酮 、 乙醇 为溶剂， 反应 7.0h， 生成 1-methyl-4-{1-methyl-4-[1-methyl-4-(3-chlorothiophene-2-carboxamido)-2-pyrrolecarboxamido]-2-pyrrolecarboxamido}-2-pyrrolecarboxylic acid
  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