1-[3-(6,7-Diethoxy-quinazolin-4-ylamino)-phenyl]-ethanone | 774532-51-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-[3-(6,7-Diethoxy-quinazolin-4-ylamino)-phenyl]-ethanone
• 英文别名: 1-[3-[(6,7-diethoxyquinazolin-4-yl)amino]phenyl]ethanone
• CAS: 774532-51-3
• 化学式: C₂₀H₂₁N₃O₃
• 分子量: 351.405
• InChiKey: QZRGWLSWQIRIHZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  73.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-[3-(6,7-Diethoxy-quinazolin-4-ylamino)-phenyl]-ethanone 在 氢溴酸 、 溴 作用下， 反应 0.33h， 以65%的产率得到2-Bromo-1-[3-(6,7-diethoxy-quinazolin-4-ylamino)-phenyl]-ethanone
  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
• 作为产物：
  描述：

  3,4-二乙氧基苯甲酸乙酯 在 10percent Pd/C ammonium carbonate 、 氢气 、 硝酸 、 溶剂黄146 、 三氯氧磷 作用下， 以 乙醇 、 异丙醇 为溶剂， 25.0~170.0 ℃ 、344.75 kPa 条件下， 反应 9.0h， 生成 1-[3-(6,7-Diethoxy-quinazolin-4-ylamino)-phenyl]-ethanone
  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

• 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.