1-(4-(iso-propyl)phenyl)-4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)butan-1-one | 185066-40-4

• 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: 1-(4-(iso-propyl)phenyl)-4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)butan-1-one
• 英文别名: 4-(4'-(hydroxy(diphenyl)methyl)piperidin-1-yl)-1-(4-isopropylphenyl)butan-1-one；4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)-1-(4-isopropylphenyl)butan-1-one；KSC-335-005；1-Keto Descarboxy 1-Deshydroxy Fexofenadine；4-[4-[hydroxy(diphenyl)methyl]piperidin-1-yl]-1-(4-propan-2-ylphenyl)butan-1-one
• CAS: 185066-40-4
• 化学式: C₃₁H₃₇NO₂
• 分子量: 455.64
• InChiKey: YRYIWJILPKRVBV-UHFFFAOYSA-N

物化性质

• 熔点：
  190-196 °C
• 沸点：
  616.3±50.0 °C(Predicted)
• 密度：
  1.091±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿；四氢呋喃；丙酮;乙腈；二氯甲烷

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(4-(iso-propyl)phenyl)-4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)butan-1-one 在 咪唑 、 sodium tetrahydroborate 、 N-溴代丁二酰亚胺(NBS) 、 四丁基氟化铵 、 双氧水 、 magnesium 作用下， 以 四氢呋喃 、 甲醇 、 四氯化碳 、 N,N-二甲基甲酰胺 为溶剂， 反应 28.75h， 生成 非索芬那定
  参考文献：
  名称：

  Novel and Efficient Method for the Synthesis of Racemic Fexofenadine

  摘要：

  [image omitted] Fexofenadine is a selective H1-histamine receptor antagonist, which is an attractive alternative treatment for allergy symptoms. An efficient and environmentally friendly synthetic approach for the preparation of fexofenadine was developed from commercially available cumene. The method involves the Friedel-Craft's reaction, substitution, reduction, bromination, and the Grignard reaction.

  DOI：

  10.1080/00397911.2010.502986
• 作为产物：
  描述：

  异丙苯 在 aluminum (III) chloride 、 potassium hydrogencarbonate 作用下， 以 5,5-dimethyl-1,3-cyclohexadiene 、 二氯甲烷 、 水 为溶剂， 反应 22.0h， 生成 1-(4-(iso-propyl)phenyl)-4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)butan-1-one
  参考文献：
  名称：

  Novel and Efficient Method for the Synthesis of Racemic Fexofenadine

  摘要：

  [image omitted] Fexofenadine is a selective H1-histamine receptor antagonist, which is an attractive alternative treatment for allergy symptoms. An efficient and environmentally friendly synthetic approach for the preparation of fexofenadine was developed from commercially available cumene. The method involves the Friedel-Craft's reaction, substitution, reduction, bromination, and the Grignard reaction.

  DOI：

  10.1080/00397911.2010.502986

文献信息

• Identification of Terfenadine as an Inhibitor of Human CD81-Receptor HCV-E2 Interaction: Synthesis and Structure Optimization
  作者：Marcel Holzer、Sigrid Ziegler、Beatrice Albrecht、Bernd Kronenberger、Artur Kaul、Ralf Bartenschlager、Lars Kattner、Christian Klein、Rolf Hartmann

  DOI：10.3390/molecules13051081

  日期：——

  Terfenadine (4-[4-(hydroxydiphenylmethyl)-1-piperidyl]-1-(4-tert-butylphenyl)-butan-1-ol) was identified in a biological screening to be a moderate inhibitor (27% inhibition) of the CD81-LEL–HCV-E2 interaction. To increase the observed biologicalactivity, 63 terfenadine derivates were synthesized via microwave assisted nucleophilicsubstitution. The prepared compounds were tested for their inhibitory potency by means ofa fluorescence labeled antibody assay using HUH7.5 cells. Distinct structure-activityrelationships could be derived. Optimization was successful, leading to 3g, identfied as themost potent compound (69 % inhibition). Experiments with viral particles revealed thatthere might be additional HCV infection reducing mechanisms.

  特非那定（4-[4-（羟二苯甲基）-1-哌啶基]-1-（4-叔丁基苯基）-丁烷-1-醇）在生物筛选中被识别为中等抑制剂（抑制率为27%），针对CD81-LEL与HCV-E2的相互作用。为了提高观察到的生物活性，通过微波辅助亲核取代合成了63个特非那定衍生物。这些制备的化合物通过使用HUH7.5细胞的荧光标记抗体检测法测试了它们的抑制效力。可以得出明显的结构-活性关系。优化取得了成功，导致了3g的识别，这是最强效的化合物（抑制率为69%）。对病毒颗粒的实验揭示可能存在额外的降低HCV感染的机制。
• METHODS AND COMPOSITIONS FOR TREATING INFECTION
  申请人：UNIVERSITY OF ROCHESTER

  公开号：US20150238473A1

  公开（公告）日：2015-08-27

  Provided herein are compositions and methods for treating or preventing infection.

  本文提供了用于治疗或预防感染的组合物和方法。
• Methods and compositions for treating infection
  申请人：UNIVERSITY OF ROCHESTER

  公开号：US10004701B2

  公开（公告）日：2018-06-26

  Provided herein are compositions and methods for treating or preventing infection.

  本文提供了用于治疗或预防感染的组合物和方法。
• 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.