3-(3-(3,4-二氯苯氧基)苯基)丙胺 | 1000567-34-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 3-(3-(3,4-二氯苯氧基)苯基)丙胺
• 英文名称: 3-(3-(3,4-dichlorophenoxy)phenyl)propylamine
• 英文别名: 3-[3-(3,4-Dichlorophenoxy)phenyl]propan-1-amine
• CAS: 1000567-34-9
• 化学式: C₁₅H₁₅Cl₂NO
• 分子量: 296.196
• InChiKey: QVBSTPIGUVPROV-UHFFFAOYSA-N

物化性质

• 沸点：
  406.4±45.0 °C(Predicted)
• 密度：
  1.250±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  35.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-(3-(3,4-二氯苯氧基)苯基)丙胺 在 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 3.0h， 生成 (Z)-4-((3-(3-(3,4-dichlorophenoxy)phenyl)propyl)amino)-2-hydroxy-4-oxobut-2-enoic acid
  参考文献：
  名称：

  HIV-1 Integrase Inhibitor-Inspired Antibacterials Targeting Isoprenoid Biosynthesis

  摘要：

  We report the discovery of antibacterial leads, keto- and diketo-acids, targeting two prenyl transferases: undecaprenyl diphosphate synthase (UPPS) and dehydrosqualene synthase (CrtM). The leads were suggested by the observation that keto- and diketo-acids bind to the active site Mg2+/Asp domain in HIV-1 integrase, and similar domains are present in prenyl transferases. We report the X-ray crystallographic structures of one diketo-acid and one keto-acid bound to CrtM, which supports the Mg2+ binding hypothesis, together with the X-ray structure of one diketo-acid bound to UPPS. In all cases, the inhibitors bind to a farnesyl diphosphate substrate-binding site. Compound 45 had cell growth inhibition MIC90 values of similar to 250-500 ng/mL against Staphylococcus aureus, 500 ng/mL against Bacillus anthracis, 4 mu g/mL against Listeria monocytogenes and Enterococcus faecium, and 1 mu g/mL against Streptococcus pyogenes M1 but very little activity against Escherichia coli (DH5 alpha, K12) or human cell lines.

  DOI：

  10.1021/ml300038t
• 作为产物：
  描述：

  在 aluminum (III) chloride 、 lithium aluminium tetrahydride 、 水 作用下， 以 四氢呋喃 为溶剂， 生成 3-(3-(3,4-二氯苯氧基)苯基)丙胺
  参考文献：
  名称：

  Inhibition of Staphyloxanthin Virulence Factor Biosynthesis in Staphylococcus aureus: In Vitro, in Vivo, and Crystallographic Results

  摘要：

  The gold color of Staphylococcus aureus is derived from the carotenoid staphyloxanthin, a virulence factor for the organism. Here, we report the synthesis and activity of a broad variety of staphyloxanthin biosynthesis inhibitors that inhibit the first committed step in its biosynthesis, condensation of two farnesyl diphosphate (FPP) molecules to dehydrosqualene, catalyzed by the enzyme dehydrosqualene synthase (CrtM). The most active compounds are phosphonoacetamides that have low nanomolar K-i values for CrtM inhibition and are active in whole bacterial cells and in mice, where they inhibit S. aureus disease progression. We also report the X-ray crystallographic structure of the most active compound, N-3-(3-phenoxyphenyl)propylphosphonoacetamide (IC50 = 8 nM, in cells), bound to CrtM. The structure exhibits a complex network of hydrogen bonds between the polar headgroup and the protein, while the 3-phenoxyphenyl side chain is located in a hydrophobic pocket previously reported to bind farnesyl thiodiphosphate (FsPP), as well as biphenyl phosphonosulfonate inhibitors. Given the good enzymatic, whole cell, and in vivo pharmacologic activities, these results should help guide the further development of novel antivirulence factor-based therapies for S. aureus infections.

  DOI：

  10.1021/jm9001764

文献信息

• ANTI-BACTERIAL COMPOSITIONS AND METHODS INCLUDING TARGETING VIRULENCE FACTORS OF STAPHYLOCOCCUS AUREUS
  申请人：Oldfield Eric

  公开号：US20120022024A1

  公开（公告）日：2012-01-26

  This disclosure relates to compositions and methods including for the inhibition, prevention, and/or treatment of microbial infections, including infections from such pathogens as Staphylococcus aureus.

  本公开涉及包括用于抑制、预防和/或治疗微生物感染的组合物和方法，包括对金黄色葡萄球菌等病原体引起的感染。
• [EN] ANTI-BACTERIAL COMPOSITIONS AND METHODS INCLUDING TARGETING VIRULENCE FACTORS OF STAPHYLOCOCCUS AUREUS<br/>[FR] COMPOSITIONS ANTI-BACTÉRIENNES ET PROCÉDÉS COMPRENANT LE CIBLAGE DE FACTEURS DE VIRULENCE DE STAPHYLOCOCCUS AUREUS
  申请人：UNIV ILLINOIS

  公开号：WO2010123599A9

  公开（公告）日：2011-02-17

  [EN] This disclosure relates to compositions and methods including for the inhibition, prevention, and/or treatment of microbial infections, including infections from such pathogens as Staphylococcus aureus.
  [FR] L'invention se rapporte à des compositions et à des procédés notamment pour l'inhibition, la prévention, et/ou le traitement d'infections microbiennes, y compris des infections par des agents pathogènes tels que Staphylococcus aureus.
• HIV-1 Integrase Inhibitor-Inspired Antibacterials Targeting Isoprenoid Biosynthesis
  作者：Yonghui Zhang、Fu-Yang Lin、Kai Li、Wei Zhu、Yi-Liang Liu、Rong Cao、Ran Pang、Eunhae Lee、Jordan Axelson、Mary Hensler、Ke Wang、Katie J. Molohon、Yang Wang、Douglas A. Mitchell、Victor Nizet、Eric Oldfield

  DOI：10.1021/ml300038t

  日期：2012.5.10

  We report the discovery of antibacterial leads, keto- and diketo-acids, targeting two prenyl transferases: undecaprenyl diphosphate synthase (UPPS) and dehydrosqualene synthase (CrtM). The leads were suggested by the observation that keto- and diketo-acids bind to the active site Mg2+/Asp domain in HIV-1 integrase, and similar domains are present in prenyl transferases. We report the X-ray crystallographic structures of one diketo-acid and one keto-acid bound to CrtM, which supports the Mg2+ binding hypothesis, together with the X-ray structure of one diketo-acid bound to UPPS. In all cases, the inhibitors bind to a farnesyl diphosphate substrate-binding site. Compound 45 had cell growth inhibition MIC90 values of similar to 250-500 ng/mL against Staphylococcus aureus, 500 ng/mL against Bacillus anthracis, 4 mu g/mL against Listeria monocytogenes and Enterococcus faecium, and 1 mu g/mL against Streptococcus pyogenes M1 but very little activity against Escherichia coli (DH5 alpha, K12) or human cell lines.
• Inhibition of Staphyloxanthin Virulence Factor Biosynthesis in <i>Staphylococcus aureus</i>: In Vitro, in Vivo, and Crystallographic Results
  作者：Yongcheng Song、Chia-I Liu、Fu-Yang Lin、Joo Hwan No、Mary Hensler、Yi-Liang Liu、Wen-Yih Jeng、Jennifer Low、George Y. Liu、Victor Nizet、Andrew H.-J. Wang、Eric Oldfield

  DOI：10.1021/jm9001764

  日期：2009.7.9

  The gold color of Staphylococcus aureus is derived from the carotenoid staphyloxanthin, a virulence factor for the organism. Here, we report the synthesis and activity of a broad variety of staphyloxanthin biosynthesis inhibitors that inhibit the first committed step in its biosynthesis, condensation of two farnesyl diphosphate (FPP) molecules to dehydrosqualene, catalyzed by the enzyme dehydrosqualene synthase (CrtM). The most active compounds are phosphonoacetamides that have low nanomolar K-i values for CrtM inhibition and are active in whole bacterial cells and in mice, where they inhibit S. aureus disease progression. We also report the X-ray crystallographic structure of the most active compound, N-3-(3-phenoxyphenyl)propylphosphonoacetamide (IC50 = 8 nM, in cells), bound to CrtM. The structure exhibits a complex network of hydrogen bonds between the polar headgroup and the protein, while the 3-phenoxyphenyl side chain is located in a hydrophobic pocket previously reported to bind farnesyl thiodiphosphate (FsPP), as well as biphenyl phosphonosulfonate inhibitors. Given the good enzymatic, whole cell, and in vivo pharmacologic activities, these results should help guide the further development of novel antivirulence factor-based therapies for S. aureus infections.