2-[4-(4-nitrophenyl)piperazin-1-ylmethyl]-4,6-dimethylisothiazolo[5,4-b]pyridin-3(2H)-one | 872170-72-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 2-[4-(4-nitrophenyl)piperazin-1-ylmethyl]-4,6-dimethylisothiazolo[5,4-b]pyridin-3(2H)-one
• 英文别名: 4,6-Dimethyl-2-[4-(4-nitrophenyl)piperazin-1-ylmethyl]isothiazolo[5,4-b]pyridin-3(2H)-one；4,6-dimethyl-2-[[4-(4-nitrophenyl)piperazin-1-yl]methyl]-[1,2]thiazolo[5,4-b]pyridin-3-one
• CAS: 872170-72-4
• 化学式: C₁₉H₂₁N₅O₃S
• 分子量: 399.473
• InChiKey: MNFQUFGMUWCABK-UHFFFAOYSA-N

物化性质

• 熔点：
  201-204 °C(Solv: methanol (67-56-1))
• 沸点：
  632.3±65.0 °C(Predicted)
• 密度：
  1.379±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  111
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  1-(4-硝基苯基)哌嗪 、 2-hydroxymethyl-4,6-dimethylisothiazolo[5,4-b]pyridin-3(2H)-one 以 乙醇 为溶剂， 反应 6.0h， 以80%的产率得到2-[4-(4-nitrophenyl)piperazin-1-ylmethyl]-4,6-dimethylisothiazolo[5,4-b]pyridin-3(2H)-one
  参考文献：
  名称：

  Synthesis, analgesic activity and computational study of new isothiazolopyridines of Mannich base type

  摘要：

  A series of new 4-arylpiperazine derivatives of isothiazolopyridine of Mannich base type and their non-4-arylpiperazine analogues (3 and 4) were synthesized and assayed as potential analgesic agents. Pharmacological assay demonstrated that all the compounds prepared, without exception, displayed significant activity in the mouse writhing assay. The analgesic action, expressed as ED50, was found to be 2-10 times more potent than that of acetylsalicylic acid and 1.5-10 times weaker than that of morphine, these being used as standards. The toxicities (LD50) of the investigated derivatives varied and ranged from 250 to 2000 mg/kg. Additionally, the computational investigations were performed in order to find correlation between molecular structure and biological effects (toxicity, analgesic action) of discussed compounds. Useful model was found for toxicity assessment.

  DOI：

  10.1016/j.farmac.2005.08.005

文献信息

• Synthesis, analgesic activity and computational study of new isothiazolopyridines of Mannich base type
  作者：W. Malinka、P. Świątek、B. Filipek、J. Sapa、A. Jezierska、A. Koll

  DOI：10.1016/j.farmac.2005.08.005

  日期：2005.11

  A series of new 4-arylpiperazine derivatives of isothiazolopyridine of Mannich base type and their non-4-arylpiperazine analogues (3 and 4) were synthesized and assayed as potential analgesic agents. Pharmacological assay demonstrated that all the compounds prepared, without exception, displayed significant activity in the mouse writhing assay. The analgesic action, expressed as ED50, was found to be 2-10 times more potent than that of acetylsalicylic acid and 1.5-10 times weaker than that of morphine, these being used as standards. The toxicities (LD50) of the investigated derivatives varied and ranged from 250 to 2000 mg/kg. Additionally, the computational investigations were performed in order to find correlation between molecular structure and biological effects (toxicity, analgesic action) of discussed compounds. Useful model was found for toxicity assessment.
• Synthesis of novel isothiazolopyridines and their in vitro evaluation against Mycobacterium and Propionibacterium acnes
  作者：Wiesław Malinka、Piotr Świątek、Małgorzata Śliwińska、Bogumiła Szponar、Andrzej Gamian、Zbigniew Karczmarzyk、Andrzej Fruziński

  DOI：10.1016/j.bmc.2013.06.027

  日期：2013.9

  In this paper we describe synthesis, structures and some physicochemical properties of 20 isothiazolopyridines 8-13 substituted differently into an isothiazole ring as well as their in vitro antibacterial assays against Mycobacterium tuberculosis H37Rv, Mycobacterium fortuitum PCM 672 and Propionibacterium acnes PCM 2400. Compound 13a was found to be the most active derivative against M. tuberculosis H37Rv, demonstrating 100% growth inhibition of microorganisms in the primary screen (minimum inhibitory concentration [MIC] 6.25 mu g/mL). Nineteen of the prepared compounds were evaluated against M. fortuitum PCM 672 and P. acnes PCM 2400 and only compounds 9 and 12d exhibited excellent activity against individual strains of microorganisms with MIC90 <1 mu g/mL. The inhibitory action of the remaining isothiazolopyridines towards the tested strains of the microorganism was low, absent, or a non-linear correlation prohibited accurate determination of MIC values. Unexpectedly, seven of the remaining isothiazolopyridines tested against M. fortuitum and P. acnes stimulated growth of the microorganisms in the range 10-50% or even more (10b) under experimental conditions. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.