4-phenyl-chloroacetophenone

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-phenyl-chloroacetophenone
• 英文别名: 1-(2-Chloro-4-phenylphenyl)ethanone
• 化学式: C₁₄H₁₁ClO
• 分子量: 230.694
• InChiKey: ITSMSPHEUFWJOP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  4-phenyl-chloroacetophenone 在 copper(ll) bromide 作用下， 以 氯仿 、 乙酸乙酯 为溶剂， 反应 2.0h， 生成
  参考文献：
  名称：

  Sterol 14α-Demethylase Structure-Based Optimization of Drug Candidates for Human Infections with the Protozoan Trypanosomatidae

  摘要：

  Sterol 14 alpha-demethylases (CYP51) are cytochrome P450 enzymes essential for sterol biosynthesis in eukaryotes and therapeutic targets for antifungal azoles. Multiple attempts to repurpose antifungals for treatment of human infections with protozoa (Trypanosomatidae) have been undertaken, yet so far none of them have revealed sufficient efficacy. VNI and its derivative VFV are two potent experimental inhibitors of Trypanosomatidae CYP51, effective in vivo against Chagas disease, visceral leishmaniasis, and sleeping sickness and currently under consideration as antiprotozoal drug candidates. However, VNI is less potent against Leishmania and drug-resistant strains of Trypanosoma cruzi and VFV, while displaying a broader spectrum of antiprotozoal activity, and is metabolically less stable. In this work we have designed, synthesized, and characterized a set of close analogues and identified two new compounds (7 and 9) that exceed VNI/VFV in their spectra of antiprotozoal activity, microsomal stability, and pharmacokinetics (tissue distribution in particular) and, like VNI/VFV, reveal no acute toxicity.

  DOI：

  10.1021/acs.jmedchem.8b01671
• 作为产物：
  描述：

  2'-氯-4'-溴苯乙酮 、 苯硼酸 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 乙醇 、 水 、 甲苯 为溶剂， 反应 3.0h， 生成 4-phenyl-chloroacetophenone
  参考文献：
  名称：

  Sterol 14α-Demethylase Structure-Based Optimization of Drug Candidates for Human Infections with the Protozoan Trypanosomatidae

  摘要：

  Sterol 14 alpha-demethylases (CYP51) are cytochrome P450 enzymes essential for sterol biosynthesis in eukaryotes and therapeutic targets for antifungal azoles. Multiple attempts to repurpose antifungals for treatment of human infections with protozoa (Trypanosomatidae) have been undertaken, yet so far none of them have revealed sufficient efficacy. VNI and its derivative VFV are two potent experimental inhibitors of Trypanosomatidae CYP51, effective in vivo against Chagas disease, visceral leishmaniasis, and sleeping sickness and currently under consideration as antiprotozoal drug candidates. However, VNI is less potent against Leishmania and drug-resistant strains of Trypanosoma cruzi and VFV, while displaying a broader spectrum of antiprotozoal activity, and is metabolically less stable. In this work we have designed, synthesized, and characterized a set of close analogues and identified two new compounds (7 and 9) that exceed VNI/VFV in their spectra of antiprotozoal activity, microsomal stability, and pharmacokinetics (tissue distribution in particular) and, like VNI/VFV, reveal no acute toxicity.

  DOI：

  10.1021/acs.jmedchem.8b01671

文献信息

• Bis(tetrazolyl)benzenes as ligands in the Suzuki reaction: Promoters or inhibitors?
  作者：A. S. Burukin、A. A. Vasil’ev、N. L. Merkulova、M. I. Struchkova、S. G. Zlotin

  DOI：10.1007/s11172-006-0224-0

  日期：2006.1

  The Suzuki cross-coupling with phenylboronic acid in the presence of the Pd(OAc)2/K3PO4/DMF catalytic system was successful for aryl bromides and somewhat poorer for aryl chlorides. Addition of 1,3-bis(tetrazol-1-yl)benzene or its analogs lowered the yields of biaryls.

  在Pd(OAc)2/K3PO4/DMF催化体系中，铃木交叉偶联与苯基硼酸的反应对芳基溴化物成功，而对芳基氯化物的反应效果稍差。添加1,3-双(四氮唑-1-基)苯或其类似物会降低双芳烃的产率。
• DE2047806
  申请人：——

  公开号：——

  公开（公告）日：——
• Sterol 14α-Demethylase Structure-Based Optimization of Drug Candidates for Human Infections with the Protozoan Trypanosomatidae
  作者：Laura Friggeri、Tatiana Y. Hargrove、Girish Rachakonda、Anna L. Blobaum、Paxtyn Fisher、Gabriel Melo de Oliveira、Cristiane França da Silva、Maria de Nazaré C. Soeiro、W. David Nes、Craig W. Lindsley、Fernando Villalta、F. Peter Guengerich、Galina I. Lepesheva

  DOI：10.1021/acs.jmedchem.8b01671

  日期：2018.12.13

  Sterol 14 alpha-demethylases (CYP51) are cytochrome P450 enzymes essential for sterol biosynthesis in eukaryotes and therapeutic targets for antifungal azoles. Multiple attempts to repurpose antifungals for treatment of human infections with protozoa (Trypanosomatidae) have been undertaken, yet so far none of them have revealed sufficient efficacy. VNI and its derivative VFV are two potent experimental inhibitors of Trypanosomatidae CYP51, effective in vivo against Chagas disease, visceral leishmaniasis, and sleeping sickness and currently under consideration as antiprotozoal drug candidates. However, VNI is less potent against Leishmania and drug-resistant strains of Trypanosoma cruzi and VFV, while displaying a broader spectrum of antiprotozoal activity, and is metabolically less stable. In this work we have designed, synthesized, and characterized a set of close analogues and identified two new compounds (7 and 9) that exceed VNI/VFV in their spectra of antiprotozoal activity, microsomal stability, and pharmacokinetics (tissue distribution in particular) and, like VNI/VFV, reveal no acute toxicity.