VUF 10554 | 1219456-94-6

• 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: VUF 10554
• 英文别名: 3-{2-[6-chloro-2-(4-methylpiperazin-1-yl)-quinazolin-4-amino]-ethyl}-thiazolidine-2,4-dione；3-[2-[[6-Chloro-2-(4-methylpiperazin-1-yl)quinazolin-4-yl]amino]ethyl]-1,3-thiazolidine-2,4-dione
• CAS: 1219456-94-6
• 化学式: C₁₈H₂₁ClN₆O₂S
• 分子量: 420.923
• InChiKey: JCUJHXGSSHVHTO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  107
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  N-甲基哌嗪 、 3-[2-[(2,6-Dichloroquinazolin-4-yl)amino]ethyl]-1,3-thiazolidine-2,4-dione 以 乙酸乙酯 为溶剂， 反应 0.17h， 以196 mg的产率得到VUF 10554
  参考文献：
  名称：

  Synthesis and QSAR of Quinazoline Sulfonamides As Highly Potent Human Histamine H₄ Receptor Inverse Agonists

  摘要：

  Hit optimization of the class of quinazoline containing histamine H-4 receptor (H4R) ligands resulted in a sulfonamide substituted analogue with high affinity for the H4R. This moiety leads to improved physicochemical properties and is believed to probe a distinct H4R binding pocket that was previously identified using pharmacophore modeling. By introducing a variety of sulfonamide substituents, the H4R affinity was optimized. The interaction of the new ligands, in combination with a set of previously published quinazoline compounds, was described by a QSAR equation. Pharmacological studies revealed that the sulfonamide analogues have excellent H4R affinity and behave as inverse agonists at the human H4R. In vivo evaluation of the potent 2-(6-chloro-2-(4-methylpiperazin-1-yl)quinazoline-4-amino)-N-phenylethanesulfonamide (54) (pK(i) = 8.31 +/- 0.10) revealed it to have anti-inflammatory activity in an animal model of acute inflammation.

  DOI：

  10.1021/jm901379s