| 1292802-63-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• CAS: 1292802-63-1
• 化学式: C₁₃H₉ClFN₃O
• 分子量: 277.685
• InChiKey: XKVIJFAECXOCFJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.63
• 重原子数：
  19.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  50.95
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  、 4-(2,3-dimethylphenyl)-1-piperazinebutanamine 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 22.0h， 生成 2-N-[4-[4-(2,3-dimethylphenyl)piperazin-1-yl]butyl]-6-fluoro-4-N-(furan-2-ylmethyl)quinazoline-2,4-diamine
  参考文献：
  名称：

  Synthesis and biological evaluation of 2,4-diaminoquinazoline derivatives as novel heat shock protein 90 inhibitors

  摘要：

  Novel 2,4-diaminoquinazoline derivatives originating from a virtual screening approach were designed, synthesized and their biological activities as heat shock protein 90 (Hsp90) inhibitors were evaluated. The prepared compounds exhibited significant anti-proliferative activities against DU-145, HT-29, HCT-116, A375P and MCF-7 cancer cell lines. The selected compounds were tested against Her2, a client protein of Hsp90, and showed significant reduction in Her2 protein expression. Compound 6b was found the most potent, reduced Her2 protein expression levels and induced Hsp70 protein expression levels significantly. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.117
• 作为产物：
  描述：

  2-氨基-5-氟苯甲酸甲酯 在 三氯氧磷 作用下， 以 乙醇 、 苯酚 为溶剂， 生成
  参考文献：
  名称：

  Synthesis and biological evaluation of 2,4-diaminoquinazoline derivatives as novel heat shock protein 90 inhibitors

  摘要：

  Novel 2,4-diaminoquinazoline derivatives originating from a virtual screening approach were designed, synthesized and their biological activities as heat shock protein 90 (Hsp90) inhibitors were evaluated. The prepared compounds exhibited significant anti-proliferative activities against DU-145, HT-29, HCT-116, A375P and MCF-7 cancer cell lines. The selected compounds were tested against Her2, a client protein of Hsp90, and showed significant reduction in Her2 protein expression. Compound 6b was found the most potent, reduced Her2 protein expression levels and induced Hsp70 protein expression levels significantly. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.117

文献信息

• 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.