(E)-N-methyl-N-[(benzofuran-7-yl)methyl]-3-(4-methylphenyl)prop-2-en-1-amine hydrochloride

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: (E)-N-methyl-N-[(benzofuran-7-yl)methyl]-3-(4-methylphenyl)prop-2-en-1-amine hydrochloride
• 英文别名: (E)-N-(benzofuran-7-ylmethyl)-N-methyl-3-(p-tolyl)prop-2-en-1-amine hydrochloride；(E)-N-(1-benzofuran-7-ylmethyl)-N-methyl-3-(4-methylphenyl)prop-2-en-1-amine;hydrochloride
• 化学式: C₂₀H₂₁NO*ClH
• 分子量: 327.854
• InChiKey: MHEIKJPQBMANLO-FXRZFVDSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.31
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  16.4
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  p-Methyl-zimtaldehyd 在 sodium tetrahydroborate 、 三溴化磷 、 potassium carbonate 作用下， 以 甲醇 、 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.52h， 生成 (E)-N-methyl-N-[(benzofuran-7-yl)methyl]-3-(4-methylphenyl)prop-2-en-1-amine hydrochloride
  参考文献：
  名称：

  Discovery of Potent Benzofuran-Derived Diapophytoene Desaturase (CrtN) Inhibitors with Enhanced Oral Bioavailability for the Treatment of Methicillin-Resistant Staphylococcus aureus (MRSA) Infections

  摘要：

  Blocking the staphyloxanthin biosynthesis process has emerged as a new promising antivirulence strategy. Previously, we first revealed that CrtN is a druggable target against infections caused by pigmented Staphylococcus aureus (S. aureus) and that naftifine was an effective CrtN inhibitor. Here, we identify a new type of benzofuran-derived CrtN inhibitor with submicromolar IC50 values that is based on the naftifine scaffold. The most potent analog, 5m, inhibits the pigment production of S. aureus Newman and three MRSA strains, with IC50 values of 0.38-5.45 nM, without any impact on the survival of four strains (up to 200 mu M). Notably, compound 5m (1 mu M) could significantly sensitize four strains to immune clearance and could effectively attenuate the virulence of three strains in vivo. Moreover, 5m was determined to be a weak antifungal reagent (MIC > 16 mu g/mL). Combined with good oral bioavailability (F = 42.2%) and excellent safety profiles, these data demonstrate that 5m may be a good candidate for the treatment of MRSA infections.

  DOI：

  10.1021/acs.jmedchem.5b01984

文献信息

• 苯并呋喃-7-烷基胺类化合物及其用途
  申请人：华东理工大学

  公开号：CN105566262B

  公开（公告）日：2017-10-27

  本发明的发明人设计、并合成了一种具有全新结构的苯并呋喃‑7‑烷基胺类化合物。经测试表明：本发明公开的苯并呋喃‑7‑烷基胺类化合物中大部分化合物对金黄色色素合成有强效的抑制活性，其中某些化合物对耐药菌(S.aureus USA400 MW2,USA300 LAC,Mu50)色素抑制活性极强，在体外显著地增强过氧化氢杀伤和增强人血液杀伤。在体内对于敏感菌株(S.aureus Newman)和两株耐药菌株(S.aureus USA400 MW2,Mu50)感染的动物模型中，可显著降低细菌在小鼠内脏(肾，心和肝)中定植。本发明为今后进一步设计开发新型抗细菌感染药物奠定了结构基础。
• Discovery of Potent Benzofuran-Derived Diapophytoene Desaturase (CrtN) Inhibitors with Enhanced Oral Bioavailability for the Treatment of Methicillin-Resistant <i>Staphylococcus aureus</i> (MRSA) Infections
  作者：Youxin Wang、Feifei Chen、Hongxia Di、Yong Xu、Qiang Xiao、Xuehai Wang、Hanwen Wei、Yanli Lu、Lingling Zhang、Jin Zhu、Chunquan Sheng、Lefu Lan、Jian Li

  DOI：10.1021/acs.jmedchem.5b01984

  日期：2016.4.14

  Blocking the staphyloxanthin biosynthesis process has emerged as a new promising antivirulence strategy. Previously, we first revealed that CrtN is a druggable target against infections caused by pigmented Staphylococcus aureus (S. aureus) and that naftifine was an effective CrtN inhibitor. Here, we identify a new type of benzofuran-derived CrtN inhibitor with submicromolar IC50 values that is based on the naftifine scaffold. The most potent analog, 5m, inhibits the pigment production of S. aureus Newman and three MRSA strains, with IC50 values of 0.38-5.45 nM, without any impact on the survival of four strains (up to 200 mu M). Notably, compound 5m (1 mu M) could significantly sensitize four strains to immune clearance and could effectively attenuate the virulence of three strains in vivo. Moreover, 5m was determined to be a weak antifungal reagent (MIC > 16 mu g/mL). Combined with good oral bioavailability (F = 42.2%) and excellent safety profiles, these data demonstrate that 5m may be a good candidate for the treatment of MRSA infections.