benzyl 4-(4-(4-fluorophenyl)-4-oxo-3-(pyridin-4-yl)butanoyl)piperidine-1-carboxylate | 188345-15-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: benzyl 4-(4-(4-fluorophenyl)-4-oxo-3-(pyridin-4-yl)butanoyl)piperidine-1-carboxylate
• 英文别名: 4-(1-benzyloxycarbonylpiperidin-4-yl)-2-(pyridin-4-yl)-1-(4-fluoro-phenyl)butane-1,4-dione；4-(1-Benzyloxycarbonylpiperidin-4-yl)-2-(4-pyridyl)-1-(4-fluorophenyl)butane-1,4-dione；benzyl 4-[4-(4-fluorophenyl)-4-oxo-3-pyridin-4-ylbutanoyl]piperidine-1-carboxylate
• CAS: 188345-15-5
• 化学式: C₂₈H₂₇FN₂O₄
• 分子量: 474.532
• InChiKey: JXZMQTSHROGQKW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  35
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  76.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  benzyl 4-(4-(4-fluorophenyl)-4-oxo-3-(pyridin-4-yl)butanoyl)piperidine-1-carboxylate 在 ammonium acetate 、 溶剂黄146 作用下， 以2.64 g的产率得到benzyl 4-(5-(4-fluorophenyl)-4-(pyridin-4-yl)-1H-pyrrol-2-yl)piperidine-1-carboxylate
  参考文献：
  名称：

  基于吡咯的系列 PfPKG 抗疟疾抑制剂的构效关系

  摘要：

  控制疟疾需要针对恶性疟原虫的新药。恶性疟原虫cGMP 依赖性蛋白激酶 (PfPKG) 是一个经过验证的靶标，其抑制剂可以阻断寄生虫生命周期的多个步骤。我们定义了抑制 PfPKG 的吡咯系列的构效关系 (SAR)。对关键药效基团进行了修改，以充分探索化学多样性并获得有关理想核心支架的知识。使用针对重组 PfPKG 和人 PKG 的体外效力来确定寄生虫酶的化合物选择性。使用伯氏疟原虫子孢子和恶性疟原虫无性血液阶段来测定多阶段抗寄生虫活性。使用表达带有取代的“看门人”残基的 PfPKG 的转基因寄生虫来评估化合物的细胞特异性。解析了与抑制剂结合的 PfPKG 的结构，并利用该结构与计算工具进行建模，以了解 SAR 并为后续先导化合物优化建立合理的策略。

  DOI：

  10.1021/acs.jmedchem.3c01795
• 作为产物：
  描述：

  4-氯羰酰四氢-吡啶羧酸苄酯 在 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 反应 4.58h， 生成 benzyl 4-(4-(4-fluorophenyl)-4-oxo-3-(pyridin-4-yl)butanoyl)piperidine-1-carboxylate
  参考文献：
  名称：

  Chemical probes of a trisubstituted pyrrole to identify its protein target(s) in Plasmodium sporozoites

  摘要：

  Malaria is a disease that has a major impact in many developing nations, especially on the African continent. There is a need to develop new therapeutics and prophylactic treatments against it. A trisubstituted pyrrole was recently found to inhibit infection of mammalian hepatocytes by Plasmodium sporozoites, but the target of this agent is not known. In this study trisubstituted pyrrole derivatives with different substituents on a piperidinyl nitrogen were prepared. We determined if modifications of the piperidinyl nitrogen would accommodate a drug-biotin linking strategy for affinity purification of the trisubstituted pyrrole's target protein(s). (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.01.010

文献信息

• Aliphatic amine substituted piperidyl diaryl pyrrole derivatives as antiprotozoal agents
  申请人：Merck & Co., Inc.

  公开号：US06432980B1

  公开（公告）日：2002-08-13

  Trisubstituted pyrroles are antiprotozoal agents useful in the treatment and prevention of protozoal diseases in human and animals, including the control of coccidiosis in poultry.

  三取代吡咯是抗原虫药物，可用于治疗和预防人类和动物的原虫病，包括控制家禽的球虫病。
• [EN] THERAPEUTIC METHODS AND COMPOUNDS<br/>[FR] PROCÉDÉS ET COMPOSÉS THÉRAPEUTIQUES
  申请人：UNIV RUTGERS

  公开号：WO2020219591A1

  公开（公告）日：2020-10-29

  The invention provides a compound of formula I: (I) or a pharmaceutically acceptable salt thereof, wherein R1-R5 Y have any of the values described in the specification, as well as compositions comprising a compound of formula I. The compounds are useful to treat malaria.

  该发明提供了一种化合物的公式I：(I)或其药用可接受的盐，其中R1-R5 Y具有规范中描述的任何值，以及包含公式I化合物的组合物。这些化合物可用于治疗疟疾。
• Aliphatic hydroxy substituted piperidyl diaryl pyrrole derivatives as antiprotozoal agents
  申请人：Merck & Co., Inc.

  公开号：US06528531B1

  公开（公告）日：2003-03-04

  Trisubstituted pyrroles are antiprotozoal agents useful in the treatment and prevention of protozoal diseases in human and animals, including the control of coccidiosis in poultry.

  三取代吡咯是抗原虫药物，可用于治疗和预防人类和动物的原虫病，包括控制家禽球虫病。
• Diaryl piperidyl pyrrole derivatives as antiprotozoal agents
  申请人：Merck & Co., Inc.

  公开号：US06291480B1

  公开（公告）日：2001-09-18

  Trisubstituted pyrroles are antiprotozoal agents useful in the treatment and prevention of protozoal diseases in human and animals, including the control of coccidiosis in poultry.

  三取代吡咯是抗原虫药物，可用于治疗和预防人类和动物的原虫病，包括在家禽中控制球虫病。
• Synthesis and SAR of 2,3-diarylpyrrole inhibitors of parasite cGMP-dependent protein kinase as novel anticoccidial agents
  作者：Tesfaye Biftu、Dennis Feng、Mitree Ponpipom、Narindar Girotra、Gui-Bai Liang、Xiaoxia Qian、Robert Bugianesi、Joseph Simeone、Linda Chang、Anne Gurnett、Paul Liberator、Paula Dulski、Penny Sue Leavitt、Tami Crumley、Andrew Misura、Terence Murphy、Sandra Rattray、Samantha Samaras、Tamas Tamas、John Mathew、Christine Brown、Don Thompson、Dennis Schmatz、Michael Fisher、Matthew Wyvratt

  DOI：10.1016/j.bmcl.2005.04.060

  日期：2005.7

  Several analogs of 2,3-diaryl pyrroles were synthesized and evaluated as inhibitors of Eimeria tenella cGMP-dependent protein kinase and in. in vivo anticoccidial assays. A 4-fluorophenyl group enhances both in vitro and in Vivo activities. The most potent analogs are the-5-(N-methyl, N-ethyl, and N-methylazetidine methyl) piperidyl derivatives 12, 23, and 34. These compounds have a broad spectrum of activity. Based on the in vivo efficacy and cost of synthesis, the N-ethyl analog 23 was chosen as a novel anticoccidial agent for a field trial. (c) 2005 Elsevier Ltd. All rights reserved.