7-Methylthio-3-carbethoxy-4-chinolinol | 26893-10-7

• 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-Methylthio-3-carbethoxy-4-chinolinol
• 英文别名: ethyl 4-hydroxy-7-(methylsulfanyl)-3-quinolinecarboxylate；ethyl 7-methylsulfanyl-4-oxo-1H-quinoline-3-carboxylate
• CAS: 26893-10-7
• 化学式: C₁₃H₁₃NO₃S
• 分子量: 263.317
• InChiKey: ATUPZSVXSGSZRI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  80.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  7-Methylthio-3-carbethoxy-4-chinolinol 在 水 、 sodium hydride 、 sodium hydroxide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 17.17h， 生成 7-(methylthio)-1-octyl-4-quinolone-3-carboxylic acid
  参考文献：
  名称：

  Structural development of a type-1 ryanodine receptor (RyR1) Ca2+-release channel inhibitor guided by endoplasmic reticulum Ca2+ assay

  摘要：

  Type-1 ryanodine receptor (RyRI) is a calcium-release channel localized on sarcoplasmic reticulum (SR) of the skeletal muscle, and mediates muscle contraction by releasing Ca2+ from the SR. Genetic mutations of RyRI are associated with skeletal muscle diseases such as malignant hyperthermia and central core diseases, in which over-activation of RyRI causes leakage of Ca2+ from the SR. We recently developed an efficient high-throughput screening system based on the measurement of Ca2+ in endoplasmic reticulum, and used it to identify oxolinic acid (1) as a novel RyRI channel inhibitor. Here, we designed and synthesized a series of quinolone derivatives based on 1 as a lead compound. Derivatives bearing a long alkyl chain at the nitrogen atom of the quinolone ring and having a suitable substituent at the 7-position of quinolone exhibited potent RyR1 channel-inhibitory activity. Among the synthesized compounds, 14h showed more potent activity than dantrolene, a known RyR1 inhibitor, and exhibited high RyR1 selectivity over RyR2 and RyR3. These compounds may be promising leads for clinically applicable RyRI channel inhibitors. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.06.076
• 作为产物：
  描述：

  3-氨基茴香硫醚 以 乙醇 为溶剂， 反应 28.0h， 生成 7-Methylthio-3-carbethoxy-4-chinolinol
  参考文献：
  名称：

  Structural development of a type-1 ryanodine receptor (RyR1) Ca2+-release channel inhibitor guided by endoplasmic reticulum Ca2+ assay

  摘要：

  Type-1 ryanodine receptor (RyRI) is a calcium-release channel localized on sarcoplasmic reticulum (SR) of the skeletal muscle, and mediates muscle contraction by releasing Ca2+ from the SR. Genetic mutations of RyRI are associated with skeletal muscle diseases such as malignant hyperthermia and central core diseases, in which over-activation of RyRI causes leakage of Ca2+ from the SR. We recently developed an efficient high-throughput screening system based on the measurement of Ca2+ in endoplasmic reticulum, and used it to identify oxolinic acid (1) as a novel RyRI channel inhibitor. Here, we designed and synthesized a series of quinolone derivatives based on 1 as a lead compound. Derivatives bearing a long alkyl chain at the nitrogen atom of the quinolone ring and having a suitable substituent at the 7-position of quinolone exhibited potent RyR1 channel-inhibitory activity. Among the synthesized compounds, 14h showed more potent activity than dantrolene, a known RyR1 inhibitor, and exhibited high RyR1 selectivity over RyR2 and RyR3. These compounds may be promising leads for clinically applicable RyRI channel inhibitors. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.06.076

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。
• 4-HYDROXYQUINOLINE-3-CARBOXAMIDES AND HYDRAZIDES AS ANTIVIRAL AGENTS
  申请人：Pharmacia & Upjohn Company LLC

  公开号：EP1042295B1

  公开（公告）日：2005-09-07
• Design, synthesis, and biological evaluation of novel 4-hydro-quinoline-3-carboxamide derivatives as an immunomodulator
  作者：Jun-Feng He、Liu-Hong Yun、Ri-Fang Yang、Zhi-Yong Xiao、Jun-Ping Cheng、Wen-Xia Zhou、Yong-Xiang Zhang

  DOI：10.1016/j.bmcl.2005.04.040

  日期：2005.6

  A series of novel quinoline-3-carboxamide derivatives were synthesized and evaluated for their immunomodulatory activity. The compounds were tested in vitro for effects on spleen lymphocyte proliferation and TNF-alpha production by macrophage. Three compounds showed immunomodulatory profiles similar to and more potent than those of linomide and FR137316 and were selected for further pharmacological studies in vivo. (c) 2005 Elsevier Ltd. All rights reserved.
• US6093732A
  申请人：——

  公开号：US6093732A

  公开（公告）日：2000-07-25