(6-ethoxy-7-isopropoxy-quinazolin-4-yl)-[3-(2-methyl-thiazol-4-yl)-phenyl]-amine

• 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: (6-ethoxy-7-isopropoxy-quinazolin-4-yl)-[3-(2-methyl-thiazol-4-yl)-phenyl]-amine
• 英文别名: 6-ethoxy-N-[3-(2-methyl-1,3-thiazol-4-yl)phenyl]-7-propan-2-yloxyquinazolin-4-amine
• 化学式: C₂₃H₂₄N₄O₂S
• 分子量: 420.535
• InChiKey: GRONMHVDAUBCOX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  97.4
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-溴-3'-硝基苯乙酮 在 盐酸 、 tin(ll) chloride 作用下， 以 乙醇 为溶剂， 反应 2.83h， 生成 (6-ethoxy-7-isopropoxy-quinazolin-4-yl)-[3-(2-methyl-thiazol-4-yl)-phenyl]-amine
  参考文献：
  名称：

  Anilinoquinazoline Inhibitors of Fructose 1,6-Bisphosphatase Bind at a Novel Allosteric Site:  Synthesis, In Vitro Characterization, and X-ray Crystallography

  摘要：

  The synthesis and in vitro structure-activity relationships (SAR) of a novel series of anilinoquinazolines as allosteric inhibitors of fructose-1,6-bisphosphatase (F16Bpase) are reported. The compounds have a different SAR as inhibitors of F16Bpase than anilinoquinazolines previously reported. Selective inhibition of F16Bpase can be attained through the addition of appropriate polar functional groups at the quinazoline 2-position, thus separating the F16Bpase inhibitory activity from the epidermal growth factor receptor tyrosine kinase inhibitory activity previously observed with similar structures. The compounds have been found to bind at a symmetry-repeated novel allosteric site at the subunit interface of the enzyme. Inhibition is brought about by binding to a loop comprised of residues 52-72, preventing the necessary participation of these residues in the assembly of the catalytic site. Mutagenesis studies have identified the key amino acid residues in the loop that are required for inhibitor recognition and binding.

  DOI：

  10.1021/jm010496a

文献信息

• Fructose 1,6-bisphosphatase inhibitors
  申请人：——

  公开号：US20030144308A1

  公开（公告）日：2003-07-31

  The present invention relates to certain quinazoline compounds which have utility in the treatment of diabetes mellitus, hypercholesterolemia, hyperlipidemia, diabetic complications and cancer. The invention also relates to pharmaceutical compositions and kits comprising such quinazoline compounds and to methods of using such compounds in the treatment of diabetes mellitus, hypercholesterolemia, hyperlipidemia, diabetic complications and cancer.

  本发明涉及某些喹唑啉化合物，其在糖尿病、高胆固醇血症、高脂血症、糖尿病并发症和癌症治疗中具有用途。该发明还涉及含有这种喹唑啉化合物的药物组合物和配套工具，以及使用这些化合物治疗糖尿病、高胆固醇血症、高脂血症、糖尿病并发症和癌症的方法。
• Anilinoquinazoline Inhibitors of Fructose 1,6-Bisphosphatase Bind at a Novel Allosteric Site:  Synthesis, In Vitro Characterization, and X-ray Crystallography
  作者：Stephen W. Wright、Anthony A. Carlo、Maynard D. Carty、Dennis E. Danley、David L. Hageman、George A. Karam、Carolyn B. Levy、Mahmoud N. Mansour、Alan M. Mathiowetz、Lester D. McClure、Nestor、R. Kirk McPherson、Jayvardhan Pandit、Leslie R. Pustilnik、Gayle K. Schulte、Walter C. Soeller、Judith L. Treadway、Ing-Kae Wang、Paul H. Bauer

  DOI：10.1021/jm010496a

  日期：2002.8.1

  The synthesis and in vitro structure-activity relationships (SAR) of a novel series of anilinoquinazolines as allosteric inhibitors of fructose-1,6-bisphosphatase (F16Bpase) are reported. The compounds have a different SAR as inhibitors of F16Bpase than anilinoquinazolines previously reported. Selective inhibition of F16Bpase can be attained through the addition of appropriate polar functional groups at the quinazoline 2-position, thus separating the F16Bpase inhibitory activity from the epidermal growth factor receptor tyrosine kinase inhibitory activity previously observed with similar structures. The compounds have been found to bind at a symmetry-repeated novel allosteric site at the subunit interface of the enzyme. Inhibition is brought about by binding to a loop comprised of residues 52-72, preventing the necessary participation of these residues in the assembly of the catalytic site. Mutagenesis studies have identified the key amino acid residues in the loop that are required for inhibitor recognition and binding.