LASSBio-998

• 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: LASSBio-998
• 英文别名: ethyl 6-(3-cyclohexylureido)-1,3-dioxolo-[4,5-g]quinoline-7-carboxylate；ethyl 6-cyclohexylureido-[1,3]dioxolo[4,5-g]quinoline-7-carboxylate；ethyl 6-(cyclohexylcarbamoylamino)-[1,3]dioxolo[4,5-g]quinoline-7-carboxylate
• 化学式: C₂₀H₂₃N₃O₅
• 分子量: 385.42
• InChiKey: XZUUCPKAWNVFSQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  98.8
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  6-硝基胡椒醛 在 aluminum oxide 、 potassium fluoride 、 四氯化钛 、 锌 作用下， 以 四氢呋喃 、 乙醇 、 甲苯 为溶剂， 反应 49.5h， 生成 LASSBio-998
  参考文献：
  名称：

  Docking, synthesis and pharmacological activity of novel urea-derivatives designed as p38 MAPK inhibitors

  摘要：

  p38 mitogen-activated protein kinase (p38 MAPK) is an important signal transducing enzyme involved in many cellular regulations, including signaling pathways, pain and inflammation. Several p38 MAPK inhibitors have been developed as drug candidates to treatment of autoimmune disorders, such as rheumatoid arthritis. In this paper we reported the docking, synthesis and pharmacological activity of novel urea-derivatives (4a-e) designed as p38 MAPK inhibitors. These derivatives presented good theoretical affinity to the target p38 MAPK, standing out compound 4e (LASSBio-998), which showed a better score value compared to the prototype GK-00687. This compound was able to reduce in vitro TNF-alpha production and was orally active in a hypernociceptive murine model sensible to p38 MAPK inhibitors. Otherwise, compound 4e presented a dose-dependent analgesic effect in a model of antigen (mBSA)-induced arthritis and anti-inflammatory profile in carrageenan induced paw edema, indicating its potential as a new antiarthritis prototype. (c) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.05.006

文献信息

• Docking, synthesis and pharmacological activity of novel urea-derivatives designed as p38 MAPK inhibitors
  作者：Raquel de Oliveira Lopes、Nelilma Correia Romeiro、Cleverton Kleiton F. de Lima、Leandro Louback da Silva、Ana Luisa Palhares de Miranda、Paulo Gustavo B.D. Nascimento、Fernando Q. Cunha、Eliezer J. Barreiro、Lídia Moreira Lima

  DOI：10.1016/j.ejmech.2012.05.006

  日期：2012.8

  p38 mitogen-activated protein kinase (p38 MAPK) is an important signal transducing enzyme involved in many cellular regulations, including signaling pathways, pain and inflammation. Several p38 MAPK inhibitors have been developed as drug candidates to treatment of autoimmune disorders, such as rheumatoid arthritis. In this paper we reported the docking, synthesis and pharmacological activity of novel urea-derivatives (4a-e) designed as p38 MAPK inhibitors. These derivatives presented good theoretical affinity to the target p38 MAPK, standing out compound 4e (LASSBio-998), which showed a better score value compared to the prototype GK-00687. This compound was able to reduce in vitro TNF-alpha production and was orally active in a hypernociceptive murine model sensible to p38 MAPK inhibitors. Otherwise, compound 4e presented a dose-dependent analgesic effect in a model of antigen (mBSA)-induced arthritis and anti-inflammatory profile in carrageenan induced paw edema, indicating its potential as a new antiarthritis prototype. (c) 2012 Elsevier Masson SAS. All rights reserved.