4-{2-[1-methyl-4-(1-methyl-4-(1-methyl-4-(4,5-dichloroisothiazole-2-carboxamido)-2-pyrrolecarboxamido)-2-pyrrolecarboxamido)-2-pyrrolecarboxamido]ethyl}morpholine | 365211-30-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-{2-[1-methyl-4-(1-methyl-4-(1-methyl-4-(4,5-dichloroisothiazole-2-carboxamido)-2-pyrrolecarboxamido)-2-pyrrolecarboxamido)-2-pyrrolecarboxamido]ethyl}morpholine
• 英文别名: 4,5-dichloro-N-[1-methyl-5-[[1-methyl-5-[[1-methyl-5-(2-morpholin-4-ylethylcarbamoyl)pyrrol-3-yl]carbamoyl]pyrrol-3-yl]carbamoyl]pyrrol-3-yl]-1,2-thiazole-3-carboxamide
• CAS: 365211-30-9
• 化学式: C₂₈H₃₁Cl₂N₉O₅S
• 分子量: 676.583
• InChiKey: KDXGCSDAESTOTN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  45
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  185
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  哌啶 、 4-{2-[1-methyl-4-(1-methyl-4-(1-methyl-4-(4,5-dichloroisothiazole-2-carboxamido)-2-pyrrolecarboxamido)-2-pyrrolecarboxamido)-2-pyrrolecarboxamido]ethyl}morpholine 反应 24.0h， 生成 4-chloro-N-[1-methyl-5-[[1-methyl-5-[[1-methyl-5-(2-morpholinoethylcarbamoyl)pyrrol-3-yl]carbamoyl]pyrrol-3-yl]carbamoyl]pyrrol-3-yl]-5-(1-piperidyl)isothiazole-3-carboxamide
  参考文献：
  名称：

  DNA Binding Ligands with Excellent Antibiotic Potency Against Drug-Resistant Gram-Positive Bacteria

  摘要：

  An efficient synthesis of DNA binding molecules consisting of four heterocyclic carboxamide units and various substituents at both termini is described. The minor-groove binding ligands showed excellent activity against a broad range of Gram-positive bacteria; no cross-resistance to known antibacterial drugs was observed. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00515-2
• 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 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 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 42.17h， 生成 4-{2-[1-methyl-4-(1-methyl-4-(1-methyl-4-(4,5-dichloroisothiazole-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