4-(2-(4-fluorophenyl)-5-(1-methylpiperidin-4-yl)-1H-pyrrol-3-yl)-2-methylpyridine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 4-(2-(4-fluorophenyl)-5-(1-methylpiperidin-4-yl)-1H-pyrrol-3-yl)-2-methylpyridine
• 英文别名: 4-[2-(4-Fluoro-phenyl)-5-(1-methyl-piperidin-4-yl)-1H-pyrrol-3-yl]-2-methyl-pyridine；4-[2-(4-fluorophenyl)-5-(1-methylpiperidin-4-yl)-1H-pyrrol-3-yl]-2-methylpyridine
• 化学式: C₂₂H₂₄FN₃
• 分子量: 349.451
• InChiKey: AUOITMPSLFBTFB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  31.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(2-(4-fluorophenyl)-5-(1-methylpiperidin-4-yl)-1H-pyrrol-3-yl)-2-methylpyridine 在 盐酸 作用下， 以 甲醇 、 二氯甲烷 、 水 、 异丙醇 为溶剂， 生成 4-(2-(4-fluorophenyl)-5-(1-methylpiperidin-4-yl)-1H-pyrrol-3-yl)-2-methylpyridine dihydrochloride
  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：

  2,4-二甲基吡啶 在 palladium on activated charcoal 乙酸铵 、 氢气 、 sodium hydride 、 溶剂黄146 、 二甲基亚砜 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-(2-(4-fluorophenyl)-5-(1-methylpiperidin-4-yl)-1H-pyrrol-3-yl)-2-methylpyridine
  参考文献：
  名称：

  Synthesis and SAR of 2,3-diarylpyrrole inhibitors of parasite cGMP-dependent protein kinase as novel anticoccidial agents

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2005.04.060

文献信息

• [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。
• THERAPEUTIC METHODS AND COMPOUNDS
  申请人：RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY

  公开号：US20220227735A1

  公开（公告）日：2022-07-21

  The invention provides a compound of formula I: (I) or a pharmaceutically acceptable salt thereof, wherein R 1 -R 5 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.
• 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.
• Structure–Activity Relationship of a Pyrrole Based Series of PfPKG Inhibitors as Anti-Malarials
  作者：John A. Gilleran、Kutub Ashraf、Melvin Delvillar、Tyler Eck、Raheel Fondekar、Edward B. Miller、Ashley Hutchinson、Aiping Dong、Alma Seitova、Mariana Laureano De Souza、David Augeri、Levon Halabelian、John Siekierka、David P. Rotella、John Gordon、Wayne E. Childers、Mark C. Grier、Bart L. Staker、Jacques Y. Roberge、Purnima Bhanot

  DOI：10.1021/acs.jmedchem.3c01795

  日期：2024.3.14

  protein kinase (PfPKG) is a validated target whose inhibitors could block multiple steps of the parasite’s life cycle. We defined the structure–activity relationship (SAR) of a pyrrole series for PfPKG inhibition. Key pharmacophores were modified to enable full exploration of chemical diversity and to gain knowledge about an ideal core scaffold. In vitro potency against recombinant PfPKG and human PKG

  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。