2-amino-5-(1-piperidyl)phenol

• 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: 2-amino-5-(1-piperidyl)phenol
• 英文别名: 2-Amino-5-(piperidin-1-yl)phenol；2-amino-5-piperidin-1-ylphenol
• 化学式: C₁₁H₁₆N₂O
• 分子量: 192.261
• InChiKey: BMRXPAHDSRDDBX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  49.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-amino-5-(1-piperidyl)phenol 在 4-二甲氨基吡啶 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 4.0h， 生成 2-oxo-N-(4-phenylbutyl)-6-piperidin-1-ium-1-yl-1,3-benzoxazole-3-carboxamide hydrochloride
  参考文献：
  名称：

  Lead Optimization of Benzoxazolone Carboxamides as Orally Bioavailable and CNS Penetrant Acid Ceramidase Inhibitors

  摘要：

  Sphingolipids (SphLs) are a diverse class of molecules that are regulated by a complex network of enzymatic pathways. A disturbance in these pathways leads to lipid accumulation and initiation of several SphL-related disorders. Acid ceramidase is one of the key enzymes that regulate the metabolism of ceramides and glycosphingolipids, which are important members of the SphL family. Herein, we describe the lead optimization studies of benzoxazolone carboxamides resulting in piperidine 22m, where we demonstrated target engagement in two animal models of neuropathic lysosomal storage diseases (LSDs), Gaucher's and Krabbe's diseases. After daily intraperitoneal administration at 90 mg kg(-1), 22m significantly reduced the brain levels of the toxic lipids glucosylsphingosine (GluSph) in 4L;C* mice and galactosylsphingosine (GalSph) in Twitcher mice. We believe that 22m is a lead molecule that can be further developed for the correction of severe neurological LSDs where GluSph or GalSph play a significant role in disease pathogenesis.

  DOI：

  10.1021/acs.jmedchem.9b02004
• 作为产物：
  描述：

  5-氟-2-硝基苯酚 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 6.0h， 生成 2-amino-5-(1-piperidyl)phenol
  参考文献：
  名称：

  2-Aminobenzoxazole ligands of the hepatitis C virus internal ribosome entry site

  摘要：

  2-Aminobenzoxazoles have been synthesized as ligands for the hepatitis C virus (HCV) internal ribosome entry site (IRES) RNA. The compounds were designed to explore the less basic benzoxazole system as a replacement for the core scaffold in previously discovered benzimidazole viral translation inhibitors. Structure-activity relationships in the target binding of substituted benzoxazole ligands were investigated. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.05.088

文献信息

• [EN] ANTIBIOTIC COMPOUNDS<br/>[FR] COMPOSÉS ANTIBIOTIQUES
  申请人：DISCUVA LTD

  公开号：WO2018037223A1

  公开（公告）日：2018-03-01

  The present invention relates to antibiotic compounds of formula (I), to compositions containing these compounds and to methods of treating bacterial diseases and infections using the compounds. The compounds find application in the treatment of infection with, and diseases caused by, Gram-positive and/or Gram-negative bacteria, and in particular in the treatment of infection with, and diseases caused by, Neisseria gonorrhoeae.

  本发明涉及公式（I）的抗生素化合物，含有这些化合物的组合物，以及使用这些化合物治疗细菌性疾病和感染的方法。这些化合物在治疗革兰氏阳性和/或革兰氏阴性细菌引起的感染和疾病方面具有应用，特别是在治疗由淋病奈瑟菌引起的感染和疾病方面。
• Formation of nitrogen-containing heterocycles using di(imidazole-1-yl)methanimine
  作者：Yong-Qian Wu、David C. Limburg、Douglas E. Wilkinson、Gregory S. Hamilton

  DOI：10.1002/jhet.5570400129

  日期：2003.1

  A mild and efficient synthesis of five- and six-membered nitrogen containing heterocyclic compounds, in which di(imidazole-1-yl)methanimine serves as a one-carbon source, is reported.

  据报道，温和有效地合成了五元​​和六元含氮杂环化合物，其中二（咪唑-1-基）甲亚胺是一个碳源。
• 2-Aminobenzoxazole ligands of the hepatitis C virus internal ribosome entry site
  作者：Kevin D. Rynearson、Brian Charrette、Christopher Gabriel、Jesus Moreno、Mark A. Boerneke、Sergey M. Dibrov、Thomas Hermann

  DOI：10.1016/j.bmcl.2014.05.088

  日期：2014.8

  2-Aminobenzoxazoles have been synthesized as ligands for the hepatitis C virus (HCV) internal ribosome entry site (IRES) RNA. The compounds were designed to explore the less basic benzoxazole system as a replacement for the core scaffold in previously discovered benzimidazole viral translation inhibitors. Structure-activity relationships in the target binding of substituted benzoxazole ligands were investigated. (C) 2014 Elsevier Ltd. All rights reserved.
• ANTIBIOTIC COMPOUNDS
  申请人：DISCUVA LTD.

  公开号：US20190194179A1

  公开（公告）日：2019-06-27

  The present invention relates to antibiotic compounds of formula (I), to compositions containing these compounds and to methods of treating bacterial diseases and infections using the compounds. The compounds find application in the treatment of infection with, and diseases caused by, Gram-positive and/or Gram-negative bacteria, and in particular in the treatment of infection with, and diseases caused by, Neisseria gonorrhoeae .
• Lead Optimization of Benzoxazolone Carboxamides as Orally Bioavailable and CNS Penetrant Acid Ceramidase Inhibitors
  作者：Simona Di Martino、Piero Tardia、Vincenzo Cilibrasi、Samantha Caputo、Marco Mazzonna、Debora Russo、Ilaria Penna、Natalia Realini、Natasha Margaroli、Marco Migliore、Daniela Pizzirani、Giuliana Ottonello、Sine Mandrup Bertozzi、Andrea Armirotti、Duc Nguyen、Ying Sun、Ernesto R. Bongarzone、Peter Lansbury、Min Liu、Renato Skerlj、Rita Scarpelli

  DOI：10.1021/acs.jmedchem.9b02004

  日期：2020.4.9

  Sphingolipids (SphLs) are a diverse class of molecules that are regulated by a complex network of enzymatic pathways. A disturbance in these pathways leads to lipid accumulation and initiation of several SphL-related disorders. Acid ceramidase is one of the key enzymes that regulate the metabolism of ceramides and glycosphingolipids, which are important members of the SphL family. Herein, we describe the lead optimization studies of benzoxazolone carboxamides resulting in piperidine 22m, where we demonstrated target engagement in two animal models of neuropathic lysosomal storage diseases (LSDs), Gaucher's and Krabbe's diseases. After daily intraperitoneal administration at 90 mg kg(-1), 22m significantly reduced the brain levels of the toxic lipids glucosylsphingosine (GluSph) in 4L;C* mice and galactosylsphingosine (GalSph) in Twitcher mice. We believe that 22m is a lead molecule that can be further developed for the correction of severe neurological LSDs where GluSph or GalSph play a significant role in disease pathogenesis.