2,6-Dichloroquinazolin-4-amine | 944895-55-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 2,6-Dichloroquinazolin-4-amine
• CAS: 944895-55-0
• 化学式: C₈H₅Cl₂N₃
• 分子量: 214.054
• InChiKey: SQYVXXSSMNSOCS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  51.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-甲基哌嗪 、 2,6-Dichloroquinazolin-4-amine 以 甲醇 为溶剂， 反应 0.08h， 生成 VUF 10351
  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
• 作为产物：
  描述：

  2,4,6-三氯喹唑啉 在 氨 作用下， 以 甲醇 为溶剂， 反应 16.0h， 生成 2,6-Dichloroquinazolin-4-amine
  参考文献：
  名称：

  Discovery of Quinazolines as Histamine H₄ Receptor Inverse Agonists Using a Scaffold Hopping Approach

  摘要：

  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.

  DOI：

  10.1021/jm800876b

文献信息

• [EN] BETA-ADRENERGIC RECEPTOR ALLOSTERIC MODULATORS<br/>[FR] MODULATEURS ALLOSTÉRIQUES DE RÉCEPTEURS BÊTA-ADRÉNERGIQUES
  申请人：UNIV CALIFORNIA

  公开号：WO2019204768A1

  公开（公告）日：2019-10-24

  Provided herein are modulators of beta-adrenergic receptors.

  这里提供了β肾上腺素受体的调节剂。
• 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.
• BETA-ADRENERGIC RECEPTOR ALLOSTERIC MODULATORS
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：US20210353626A1

  公开（公告）日：2021-11-18

  Provided herein are modulators of beta-adrenergic receptors.