N-(4-chloro-3-methylphenyl)piperidin-4-amine | 886506-69-0

• 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: N-(4-chloro-3-methylphenyl)piperidin-4-amine
• 英文别名: 4-Piperidinamine, N-(4-chloro-3-methylphenyl)-
• CAS: 886506-69-0
• 化学式: C₁₂H₁₇ClN₂
• 分子量: 224.733
• InChiKey: QNHYLFRZAFQSHH-UHFFFAOYSA-N

物化性质

• 沸点：
  373.0±42.0 °C(Predicted)
• 密度：
  1.148±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  24.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  phenyl (5-chlorothiazol-2-yl)carbamate 、 N-(4-chloro-3-methylphenyl)piperidin-4-amine 在 caesium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 5.0h， 以11%的产率得到4-((4-chloro-3-methylphenyl)amino)-N-(5-chlorothiazol-2-yl)piperidine-1-carboxamide
  参考文献：
  名称：

  Optimization of 5-substituted thiazolyl ureas and 6-substituted imidazopyridines as potential HIV-1 latency reversing agents

  摘要：

  A persistent latent reservoir of virus in CD4(+) T cells is a major barrier to cure HIV. Activating viral transcription in latently infected cells using small molecules is one strategy being explored to eliminate latency. We previously described the use of a FlpIn.FM HEK293 cellular assay to identify and then optimize the 2-acylaminothiazole class to exhibit modest activation of HIV gene expression. Here, we implement two strategies to further improve the activation of viral gene expression and physicochemical properties of this class. Firstly, we explored rigidification of the central oxy-carbon linker with a variety of saturated heterocycles, and secondly, investigated bioisosteric replacement of the 2-acylaminothiazole moiety. The optimization process afforded lead compounds (74 and 91) from the 2-piperazinyl thiazolyl urea and the imidazopyridine class. The lead compounds from each class demonstrate potent activation of HIV gene expression in the FlpIn.FM HEK293 cellular assay (both with LTR EC(50)s of 80 nM) and in the Jurkat Latency 10.6 cell model (LTR EC50 220 and 320 nM respectively), but consequently activate gene expression non-specifically in the FlpIn.FM HEK293 cellular assay (CMV EC50 70 and 270 nM respectively) manifesting in cellular cytotoxicity. The lead compounds have potential for further development as novel latency reversing agents. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112254
• 作为产物：
  描述：

  1-Boc-4-氨基哌啶 在 palladium diacetate 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 15.0h， 生成 N-(4-chloro-3-methylphenyl)piperidin-4-amine
  参考文献：
  名称：

  Optimization of 5-substituted thiazolyl ureas and 6-substituted imidazopyridines as potential HIV-1 latency reversing agents

  摘要：

  A persistent latent reservoir of virus in CD4(+) T cells is a major barrier to cure HIV. Activating viral transcription in latently infected cells using small molecules is one strategy being explored to eliminate latency. We previously described the use of a FlpIn.FM HEK293 cellular assay to identify and then optimize the 2-acylaminothiazole class to exhibit modest activation of HIV gene expression. Here, we implement two strategies to further improve the activation of viral gene expression and physicochemical properties of this class. Firstly, we explored rigidification of the central oxy-carbon linker with a variety of saturated heterocycles, and secondly, investigated bioisosteric replacement of the 2-acylaminothiazole moiety. The optimization process afforded lead compounds (74 and 91) from the 2-piperazinyl thiazolyl urea and the imidazopyridine class. The lead compounds from each class demonstrate potent activation of HIV gene expression in the FlpIn.FM HEK293 cellular assay (both with LTR EC(50)s of 80 nM) and in the Jurkat Latency 10.6 cell model (LTR EC50 220 and 320 nM respectively), but consequently activate gene expression non-specifically in the FlpIn.FM HEK293 cellular assay (CMV EC50 70 and 270 nM respectively) manifesting in cellular cytotoxicity. The lead compounds have potential for further development as novel latency reversing agents. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112254

文献信息

• [EN] INHIBITORS OF BACTERIAL GLYCOSYL TRANSFERASES<br/>[FR] INHIBITEURS DE GLYCOSYL TRANSFÉRASES BACTÉRIENNES
  申请人：HARVARD COLLEGE

  公开号：WO2016191658A1

  公开（公告）日：2016-12-01

  Described herein are compounds of Formula (I'), Formula (IA), Formulae (I)-(VII), pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrug sthereof. The invention also provides pharmaceutical compositions of the compounds for human and veterinary use. Compounds of the present invention are useful for inhibiting bacterial growth and therefore are useful in treating and/or preventing bacterial infections. Methods of using the compounds for treating and/or preventing a bacterial infection in a subject are also described.

  本文描述了式(I')、式(IA)、式(I)-(VII)的化合物，以及这些化合物的药用盐、溶剂合物、水合物、多型体、共晶体、互变异构体、立体异构体、同位素标记衍生物和前药。本发明还提供了这些化合物的用于人类和兽医用途的药物组合物。本发明的化合物对抑制细菌生长有用，因此在治疗和/或预防细菌感染方面具有用途。还描述了使用这些化合物治疗和/或预防受试者细菌感染的方法。
• INHIBITORS OF BACTERIAL GLYCOSYL TRANSFERASES
  申请人：President and Fellows of Harvard College

  公开号：EP3303338A1

  公开（公告）日：2018-04-11