4-((4-(hydroxydiphenylmethyl)piperidin-1-yl)methyl)benzoic acid | 192565-83-6

• 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: 4-((4-(hydroxydiphenylmethyl)piperidin-1-yl)methyl)benzoic acid
• 英文别名: Benzoic acid, 4-[[4-(hydroxydiphenylmethyl)-1-piperidinyl]methyl]-；4-[[4-[hydroxy(diphenyl)methyl]piperidin-1-yl]methyl]benzoic acid
• CAS: 192565-83-6
• 化学式: C₂₆H₂₇NO₃
• 分子量: 401.505
• InChiKey: YDQNXFIMUXRGPA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  60.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  methyl 4-((4-(hydroxydiphenylmethyl)piperidin-1-yl)methyl)benzoate 在 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 0.25h， 以74%的产率得到4-((4-(hydroxydiphenylmethyl)piperidin-1-yl)methyl)benzoic acid
  参考文献：
  名称：

  Development of Fluorine-18 Labeled Metabolically Activated Tracers for Imaging of Drug Efflux Transporters with Positron Emission Tomography

  摘要：

  Increased activity of efflux transporters, e.g., P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), at the blood brain barrier is a pathological hallmark of many neurological diseases, and the resulting multiple drug resistance represents a major clinical challenge. Noninvasive imaging of transporter activity can help to clarify the underlying mechanisms of drug resistance and facilitate diagnosis, patient stratification, and treatment monitoring. We have developed a metabolically activated radiotracer for functional imaging of P-gp/BCRP activity with positron emission tomography (PET). In preclinical studies, the tracer showed excellent initial brain uptake and clean conversion to the desired metabolite, although at a sluggish rate. Blocking with P-gp/BCRP modulators led to increased levels of brain radioactivity; however, dynamic PET did not show differential clearance rates between treatment and control groups. Our results provide proof-of-concept for development of prodrug tracers for imaging of P- /BCRP function in vivo but also highlight some challenges associated with this strategy.

  DOI：

  10.1021/acs.jmedchem.5b00652

文献信息

• 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.
• Development of Fluorine-18 Labeled Metabolically Activated Tracers for Imaging of Drug Efflux Transporters with Positron Emission Tomography
  作者：Kerstin Sander、Eva Galante、Thibault Gendron、Elena Yiannaki、Niral Patel、Tammy L. Kalber、Adam Badar、Mathew Robson、Sean P. Johnson、Florian Bauer、Severin Mairinger、Johann Stanek、Thomas Wanek、Claudia Kuntner、Tim Kottke、Lilia Weizel、David Dickens、Kjell Erlandsson、Brian F. Hutton、Mark F. Lythgoe、Holger Stark、Oliver Langer、Matthias Koepp、Erik Årstad

  DOI：10.1021/acs.jmedchem.5b00652

  日期：2015.8.13

  Increased activity of efflux transporters, e.g., P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), at the blood brain barrier is a pathological hallmark of many neurological diseases, and the resulting multiple drug resistance represents a major clinical challenge. Noninvasive imaging of transporter activity can help to clarify the underlying mechanisms of drug resistance and facilitate diagnosis, patient stratification, and treatment monitoring. We have developed a metabolically activated radiotracer for functional imaging of P-gp/BCRP activity with positron emission tomography (PET). In preclinical studies, the tracer showed excellent initial brain uptake and clean conversion to the desired metabolite, although at a sluggish rate. Blocking with P-gp/BCRP modulators led to increased levels of brain radioactivity; however, dynamic PET did not show differential clearance rates between treatment and control groups. Our results provide proof-of-concept for development of prodrug tracers for imaging of P- /BCRP function in vivo but also highlight some challenges associated with this strategy.