7,8-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid | 228728-17-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 7,8-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
• 英文别名: 7,8-Difluoro-4-hydroxyquinoline-3-carboxylic acid；7,8-difluoro-4-oxo-1H-quinoline-3-carboxylic acid
• CAS: 228728-17-4
• 化学式: C₁₀H₅F₂NO₃
• 分子量: 225.151
• InChiKey: NGWHDXXMYRPDOB-UHFFFAOYSA-N

物化性质

• 沸点：
  393.1±42.0 °C(Predicted)
• 密度：
  1.653±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  7,8-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 在 二苯醚 作用下， 生成 7,8-二氟-4-羟基喹啉
  参考文献：
  名称：

  Discovery of piperidine ethers as selective orexin receptor antagonists (SORAs) inspired by filorexant

  摘要：

  Highly selective orexin receptor antagonists (SORAs) of the orexin 2 receptor (OX2R) have become attractive targets both as potential therapeutics for insomnia as well as biological tools to help further elucidate the underlying pharmacology of the orexin signaling pathway. Herein, we describe the discovery of a novel piperidine ether 2-SORA class identified by systematic lead optimization beginning with filorexant, a dual orexin receptor antagonist (DORA) that recently completed Phase 2 clinical trials. Changes to the ether linkage and pendant heterocycle of filorexant were found to impart significant selectivity for OX2R, culminating in lead compound PE-6. PE-6 displays sub-nanomolar binding affinity and functional potency on OX2R while maintaining >1600-fold binding selectivity and >200-fold functional selectivity versus the orexin 1 receptor (OX1R). PE-6 bears a clean off-target profile, a good overall preclinical pharmacokinetic (PK) profile, and reduces wakefulness with increased NREM and REM sleep when evaluated in vivo in a rat sleep study. Importantly, subtle structural changes to the piperidine ether class impart dramatic changes in receptor selectivity. To this end, our laboratories have identified multiple piperidine ether 2-SORAs, 1-SORAs, and DORAs, providing access to a number of important biological tool compounds from a single structural class. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.12.056
• 作为产物：
  描述：

  Ethyl-7,8-difluoro-4-hydroxy-quinoline-3-carboxylate 在 lithium hydroxide 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 7,8-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
  参考文献：
  名称：

  4-hydroxyquinoline-3-carboxamides and hydrazides as antiviral agents

  摘要：

  本发明提供了式I的4-羟基喹啉-3-甲酰胺和肼化合物。这些化合物可用于治疗或预防疱疹病毒感染，特别是人类巨细胞病毒感染。

  公开号：

  US06093732A1

文献信息

• 4-hydroxyquinoline-3-carboxamides and hydrazides as antiviral agents
  申请人：Pharmacia & Upjohn Company

  公开号：US06093732A1

  公开（公告）日：2000-07-25

  The present invention provides 4-hydroxyquinoline-3-carboxamide and hydrazide compounds of formula I ##STR1## These compounds are useful to treat or prevent the herpesviral infections, particularly, human cytomegaloviral infection.

  本发明提供了式I的4-羟基喹啉-3-甲酰胺和肼化合物。这些化合物可用于治疗或预防疱疹病毒感染，特别是人类巨细胞病毒感染。
• [EN] 4-HYDROXYQUINOLINE-3-CARBOXAMIDES AND HYDRAZIDES AS ANTIVIRAL AGENTS<br/>[FR] 4-HYDROXYQUINOLINE-3-CARBOXAMIDES ET HYDRAZIDES UTILISES COMME AGENTS ANTIVIRAUX
  申请人：PHARMACIA & UPJOHN COMPANY

  公开号：WO1999032450A1

  公开（公告）日：1999-07-01

  (EN) The present invention provides 4-hydroxyquinoline-3-carboxamide and hydrazide compounds of formula (I). These compounds are useful to treat or prevent the herpesviral infections, particularly, human cytomegaloviral infection.(FR) La présente invention concerne des composés de 4-hydroxyquinoline-3-carboxamide et d'hydrazide représentés par la formule (I). Ces composés servent dans le traitement ou la prévention d'infections à virus herpétique, en particulier, de l'infection à cytomégalovirus humain.

  本发明提供了公式（I）的4-羟基喹啉-3-羧酰胺和肼类化合物。这些化合物可用于治疗或预防疱疹病毒感染，特别是人类巨细胞病毒感染。
• NOUVEAUX DERIVES DE LA BENZO f]NAPHTYRIDINE, LEUR PREPARATION ET LES COMPOSITIONS LES CONTENANT
  申请人：Aventis Pharma S.A.

  公开号：EP1189903A1

  公开（公告）日：2002-03-27
• NOUVEAUX DERIVES DE LA BENZO[f]NAPHTYRIDINE, LEUR PREPARATION ET LES COMPOSITIONS LES CONTENANT
  申请人：Aventis Pharma S.A.

  公开号：EP1189903B1

  公开（公告）日：2003-05-28
• US6093732A
  申请人：——

  公开号：US6093732A

  公开（公告）日：2000-07-25