4-hydroxy-3-[2-(3-nitrophenylamino)thiazol-4-yl]chromen-2-one | 944549-00-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 4-hydroxy-3-[2-(3-nitrophenylamino)thiazol-4-yl]chromen-2-one
• 英文别名: 4-Hydroxy-3-[2-(3-nitroanilino)-1,3-thiazol-4-yl]chromen-2-one
• CAS: 944549-00-2
• 化学式: C₁₈H₁₁N₃O₅S
• 分子量: 381.368
• InChiKey: XZAVSRMRDSNEFT-UHFFFAOYSA-N

物化性质

• 沸点：
  636.5±65.0 °C(predicted)
• 密度：
  1.623±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  146
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  间硝基苯胺 以 乙醇 、 水 为溶剂， 生成 4-hydroxy-3-[2-(3-nitrophenylamino)thiazol-4-yl]chromen-2-one
  参考文献：
  名称：

  Biochemical and pharmacological evaluation of 4-hydroxychromen-2-ones bearing polar C-3 substituents as anticoagulants

  摘要：

  The objective of this study was to investigate in vitro and in vivo anticoagulant activity of sixteen 4-hydroxycoumarin derivatives bearing polar C-3 scaffolds. The activity was evaluated by measuring prothrombin time. Enhanced anticoagulant activity in vitro was observed for all tested compounds. Upon successive administration of 0.5 mg/kg of body weight to adult Wistar rats, over a period of five days, four derivatives (2b, 4c, 5c and 9c) presented anticoagulant activity in vivo. The most active compound was 2b, with PT = 30.0 s. Low or non-toxic effects in vivo were determined based on the catalytic activity of liver enzymes and the concentration of bilirubin, iron and proteins. Metabolic pathways of the most active compounds in vivo were determined after GC/MS analysis of collected rat urine samples. The excretion occurs by glucuronidation of 7-hydroxy forms of tested derivatives. In vivo results were described using PLS-based CoMFA and CoMSIA 3D-QSAR studies, which showed CoMFA-SE (q(2) = 0.738) and CoMSIA-SEA (q(2) = 0.763) to be the statistically most relevant models. Furthermore, molecular docking and DFT mechanistic studies performed on the rat VKORC1 homology model revealed interactions between the 4-OH coumarin group in the form of phenolic anion and the Cys135 catalytic site in the transition state. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.04.036

文献信息

• Synthesis and Antimicrobial Evaluation of Some Novel 2‐Aminothiazole Derivatives of 4‐Hydroxy‐chromene‐2‐one
  作者：Nenad Vukovic、Slobodan Sukdolak、Slavica Solujic、Tanja Milosevic

  DOI：10.1002/ardp.200700215

  日期：2008.8

  Syntheses of 2‐aminothiazole derivatives of 4‐hydroxy‐chromene‐2‐one 2c–10c are reported in this paper. These compounds 2c–10c were prepared from 3‐(2‐bromoacetyl)‐4‐hydroxy‐chromene‐2‐one 1 and corresponding thiourea derivatives 2b–10b using Hantzsch reaction. The structures of all compounds were confirmed by IR and 1H‐NMR spectroscopy and elemental analyses. The molecules 2c–10c were evaluated for in vitro

  本文报道了 4-羟基色烯-2-one 2c-10c 的 2-氨基噻唑衍生物的合成。这些化合物 2c-10c 是使用 Hantzsch 反应由 3-(2-溴乙酰基)-4-羟基-色烯-2-one 1 和相应的硫脲衍生物 2b-10b 制备的。所有化合物的结构均通过 IR 和 1H-NMR 光谱和元素分析证实。评估了分子 2c-10c 对 10 种细菌和 12 种真菌的体外抗菌活性。所有测试的化合物都表现出抗菌和抗真菌活性。
• Biochemical and pharmacological evaluation of 4-hydroxychromen-2-ones bearing polar C-3 substituents as anticoagulants
  作者：Milan Mladenović、Mirjana Mihailović、Desanka Bogojević、Nenad Vuković、Slobodan Sukdolak、Sanja Matić、Neda Nićiforović、Vladimir Mihailović、Pavle Mašković、Miroslav M. Vrvić、Slavica Solujić

  DOI：10.1016/j.ejmech.2012.04.036

  日期：2012.8

  The objective of this study was to investigate in vitro and in vivo anticoagulant activity of sixteen 4-hydroxycoumarin derivatives bearing polar C-3 scaffolds. The activity was evaluated by measuring prothrombin time. Enhanced anticoagulant activity in vitro was observed for all tested compounds. Upon successive administration of 0.5 mg/kg of body weight to adult Wistar rats, over a period of five days, four derivatives (2b, 4c, 5c and 9c) presented anticoagulant activity in vivo. The most active compound was 2b, with PT = 30.0 s. Low or non-toxic effects in vivo were determined based on the catalytic activity of liver enzymes and the concentration of bilirubin, iron and proteins. Metabolic pathways of the most active compounds in vivo were determined after GC/MS analysis of collected rat urine samples. The excretion occurs by glucuronidation of 7-hydroxy forms of tested derivatives. In vivo results were described using PLS-based CoMFA and CoMSIA 3D-QSAR studies, which showed CoMFA-SE (q(2) = 0.738) and CoMSIA-SEA (q(2) = 0.763) to be the statistically most relevant models. Furthermore, molecular docking and DFT mechanistic studies performed on the rat VKORC1 homology model revealed interactions between the 4-OH coumarin group in the form of phenolic anion and the Cys135 catalytic site in the transition state. (C) 2012 Elsevier Masson SAS. All rights reserved.