[1-(4-methyl-benzyl)-piperidin-4-yl]-diphenyl-methanol | 192565-82-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: [1-(4-methyl-benzyl)-piperidin-4-yl]-diphenyl-methanol
• 英文别名: (1-(4-methylbenzyl)piperidin-4-yl)diphenylmethanol；[1-[(4-methylphenyl)methyl]piperidin-4-yl]-diphenylmethanol
• CAS: 192565-82-5
• 化学式: C₂₆H₂₉NO
• 分子量: 371.522
• InChiKey: DIADJINIBFEMEL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  α,α-二苯基-4-哌啶甲醇 、 4-甲基苄溴 在 三乙胺 作用下， 以 乙腈 为溶剂， 反应 4.0h， 以61%的产率得到[1-(4-methyl-benzyl)-piperidin-4-yl]-diphenyl-methanol
  参考文献：
  名称：

  Repurposing the Antihistamine Terfenadine for Antimicrobial Activity against Staphylococcus aureus

  摘要：

  Staphylococcus aureus is a rapidly growing health threat in the U.S., with resistance to several commonly prescribed treatments. A high-throughput screen identified the antihistamine terfenadine to possess, previously unreported, antimicrobial activity against S. aureus and other Gram-positive bacteria. In an effort to repurpose this drug, structure-activity relationship studies yielded 84 terfenadine-based analogues with several modifications providing increased activity versus S. aureus and other bacterial pathogens, including Mycobacterium tuberculosis. Mechanism of action studies revealed these compounds to exert their antibacterial effects, at least in part, through inhibition of the bacterial type II topoisomerases. This scaffold suffers from hERG liabilities which were not remedied through this round of optimization; however, given the overall improvement in activity of the set, terfenadine-based analogues provide a novel structural class of antimicrobial compounds with potential for further characterization as part of the continuing process to meet the current need for new antibiotics.

  DOI：

  10.1021/jm5010682

文献信息

• Structural determinants for histamine H1 affinity, hERG affinity and QTc prolongation in a series of terfenadine analogs
  作者：Robert Aslanian、John J. Piwinski、Xiaohong Zhu、Tony Priestley、Steve Sorota、Xiao-Yi Du、Xue-Song Zhang、Robbie L. McLeod、Robert E. West、Shirley M. Williams、John A. Hey

  DOI：10.1016/j.bmcl.2009.07.047

  日期：2009.9

  In the late 1980's reports linking the non-sedating antihistamines terfenadine and astemizole with torsades de pointes, a form of ventricular tachyarrhythmia that can degenerate into ventricular fibrillation and sudden death, appeared in the clinical literature. A substantial body of evidence demonstrates that the arrhythmogenic effect of these cardiotoxic antihistamines, as well as a number of structurally related compounds, results from prolongation of the QT interval due to suppression of specific delayed rectifier ventricular K+ currents via blockade of the hERG-IKr channel. In order to better understand the structural requirements for hERG and H-1 binding for terfenadine, a series of analogs of terfenadine has been prepared and studied in both in vitro and in vivo hERG and H-1 assays. (C) 2009 Elsevier Ltd. All rights reserved.
• Repurposing the Antihistamine Terfenadine for Antimicrobial Activity against <i>Staphylococcus aureus</i>
  作者：Jessamyn I. Perlmutter、Lauren T. Forbes、Damian J. Krysan、Katherine Ebsworth-Mojica、Jennifer M. Colquhoun、Jenna L. Wang、Paul M. Dunman、Daniel P. Flaherty

  DOI：10.1021/jm5010682

  日期：2014.10.23

  Staphylococcus aureus is a rapidly growing health threat in the U.S., with resistance to several commonly prescribed treatments. A high-throughput screen identified the antihistamine terfenadine to possess, previously unreported, antimicrobial activity against S. aureus and other Gram-positive bacteria. In an effort to repurpose this drug, structure-activity relationship studies yielded 84 terfenadine-based analogues with several modifications providing increased activity versus S. aureus and other bacterial pathogens, including Mycobacterium tuberculosis. Mechanism of action studies revealed these compounds to exert their antibacterial effects, at least in part, through inhibition of the bacterial type II topoisomerases. This scaffold suffers from hERG liabilities which were not remedied through this round of optimization; however, given the overall improvement in activity of the set, terfenadine-based analogues provide a novel structural class of antimicrobial compounds with potential for further characterization as part of the continuing process to meet the current need for new antibiotics.