VUF 10349 | 1001065-60-6

• 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 10349
• 英文别名: 6-chloro-N-methyl-2-(4-methylpiperazin-1-yl)quinazolin-4-amine；6-Chloro-4-(N-methylamino)-2-(4-methylpiperazinyl)-quinazoline
• CAS: 1001065-60-6
• 化学式: C₁₄H₁₈ClN₅
• 分子量: 291.783
• InChiKey: GNITVWLUINGTBR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  44.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  N-甲基哌嗪 、 2,6-dichloro-N-methylquinazolin-4-amine 以 乙酸乙酯 为溶剂， 反应 0.08h， 以308 mg的产率得到VUF 10349
  参考文献：
  名称：

  Quinazolines and Related Heterocyclic Compounds, and Their Therapeutic Use

  摘要：

  与组织胺H4受体相互作用的化合物，可能用于治疗或预防由组织胺H4受体介导的疾病和症状，如炎症，其化学式为(I)，其中Q为CR1或N；X为CR2或N，前提是Q和X不同时为N；Y为CR3或N；Z为CH或N；R1、R2、R3、R4、R5和R6独立地为H、F、Cl、Br、I或可选择含有一个或多个杂原子的碳氢基团；R7为包含一个或多个N原子的杂环基团；或其药用盐、酯或溶剂化合物。

  公开号：

  US20100016293A1

文献信息

• Quinazolines and Related Heterocyclic Compounds, and Their Therapeutic Use
  申请人：Smits Rogier Adriaan

  公开号：US20100016293A1

  公开（公告）日：2010-01-21

  Compounds that interact with the histamine H4 receptor, and which may be useful for treating or preventing disorders and conditions mediated by the histamine H4 receptor, e.g. inflammation, are of formula (I) wherein Q is CR 1 or N; X is CR 2 or N, provided that Q and X are not both N; Y is CR 3 or N; Z is CH or N; R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are independently H, F, Cl, Br, I, or a hydrocarbon group which optionally contains one or more heteroatoms; and R7 is a heterocyclic radical including one or more N atoms; or a pharmaceutically acceptable salt, ester or solvate thereof.

  与组织胺H4受体相互作用的化合物，可能用于治疗或预防由组织胺H4受体介导的疾病和症状，如炎症，其化学式为(I)，其中Q为CR1或N；X为CR2或N，前提是Q和X不同时为N；Y为CR3或N；Z为CH或N；R1、R2、R3、R4、R5和R6独立地为H、F、Cl、Br、I或可选择含有一个或多个杂原子的碳氢基团；R7为包含一个或多个N原子的杂环基团；或其药用盐、酯或溶剂化合物。
• Design, Synthesis, and Structure–Activity Relationships of Highly Potent 5-HT₃ Receptor Ligands
  作者：Mark H. P. Verheij、Andrew J. Thompson、Jacqueline E. van Muijlwijk-Koezen、Sarah C. R. Lummis、Rob Leurs、Iwan J. P. de Esch

  DOI：10.1021/jm300801u

  日期：2012.10.25

  The 5-HT3 receptor, a pentameric ligand-gated ion channel (pLGIC), is an important therapeutic target. During a recent fragment screen, 6-chloro-N-methyl-2-(4-methyl-1,4-diazepan-1-yl)quinazolin-4-amine (1) was identified as a 5-HT3R hit fragment. Here we describe the synthesis and structure activity relationships (SAR) of a series of (iso)quinoline and quinazoline compounds that were synthesized and screened for 5-HT3R affinity using a [H-3]granisetron displacement assay. These studies resulted in the discovery of several high affinity ligands of which compound 22 showed the highest affinity (pK(i) > 10) for the 5-HT3 receptor. The observed SAR is in agreement with established pharmacophore models for 5-HT3 ligands and is used for ligand-receptor binding mode prediction using homology modeling and in silico docking approaches.
• Discovery of Quinazolines as Histamine H₄ Receptor Inverse Agonists Using a Scaffold Hopping Approach
  作者：Rogier A. Smits、Iwan J. P. de Esch、Obbe P. Zuiderveld、Joachim Broeker、Kamonchanok Sansuk、Elena Guaita、Gabriella Coruzzi、Maristella Adami、Eric Haaksma、Rob Leurs

  DOI：10.1021/jm800876b

  日期：2008.12.25

  From a series of small fragments that was designed to probe the histamine H-4 receptor (H4R), we previously described quinoxaline-containing fragments that were grown into high affinity H4R ligands in a process that was guided by pharmacophore modeling. With a scaffold hopping exercise and using the same in silico models, we now report the identification and optimization of a series of quinazoline-containing H4R compounds. This approach led to the discovery of 6-chloi-o-N-(furan-3-yl)methyl)2-(4-methylpiperzin-1-yl)quinazolin-4-amine (VUF10499, 54) and 6-chloro-2-(4-methylpiperazin-1-yl)-N-(thiophen-2-ylmethyl)quinazolin-4-amine (VUF10497, 55) as potent human H4R inverse agonists (pK(i) = 8.12 and 7.57, respectively). Interestingly, both compounds also possess considerable affinity for the human histamine Hi receptor (H1R) and therefore represent a novel class of dual action H1R/H4R ligands, a profile that potentially leads to added therapeutic benefit. Compounds from this novel series of quirlazolines are antagonists at the rat H4R and were found to possess anti-inflammatory properties in vivo in the rat.