methyl 4-((2S,4R)-1-acetyl-2-methyl-4-(p-tolylamino)-1,2,3,4-tetrahydroquinolin-6-yl)benzoate | 1300691-47-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: methyl 4-((2S,4R)-1-acetyl-2-methyl-4-(p-tolylamino)-1,2,3,4-tetrahydroquinolin-6-yl)benzoate
• CAS: 1300691-47-7
• 化学式: C₂₇H₂₈N₂O₃
• 分子量: 428.531
• InChiKey: FBKBFGDJAUCDPN-AVRWGWEMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.75
• 重原子数：
  32.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  58.64
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  methyl 4-((2S,4R)-1-acetyl-2-methyl-4-(p-tolylamino)-1,2,3,4-tetrahydroquinolin-6-yl)benzoate 在 sodium hydroxide 、 溶剂黄146 作用下， 以 乙醇 、 水 为溶剂， 反应 1.0h， 生成 4-((2S,4R)-1-acetyl-2-methyl-4-(p-tolylamino)-1,2,3,4-tetrahydroquinolin-6-yl)benzoic acid
  参考文献：
  名称：

  The Discovery of I-BET726 (GSK1324726A), a Potent Tetrahydroquinoline ApoA1 Up-Regulator and Selective BET Bromodomain Inhibitor

  摘要：

  Through their function as epigenetic readers of the histone code, the BET family of bromodomain-containing proteins regulate expression of multiple genes of therapeutic relevance, including those involved in tumor cell growth and inflammation. BET bromodomain inhibitors have profound antiproliferative and anti-inflammatory effects which. translate into efficacy in oncology and inflammation models, and the first compounds have now progressed into clinical trials. The exciting biology of the BETs has led to great interest in the discovery of novel inhibitor classes. Here we describe the identification of a novel tetrahydroquinoline series through up-regulation of apoliproprotein A1 and the optimization into potent compounds active in murine models of septic shock and neuroblastoma. At the molecular level, these effects are produced by inhibiton of BET bromodomains X-rays crystallography reveals the interactions explaining the structure-activity relationships of binding. The resulting lead molecule, I-BET726, represents a new, potent, and selective class of tetrahydroquinoline-based BET inhibitors.

  DOI：

  10.1021/jm5010539
• 作为产物：
  描述：

  methyl 4-[1-acetyl-4-(formylamino)-2-methyl-1,2,3,4-tetrahydro-6-quinolinyl]benzoate 在 盐酸 、 L-乳酸 、 copper diacetate 、 三乙胺 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 4.33h， 生成 methyl 4-((2S,4R)-1-acetyl-2-methyl-4-(p-tolylamino)-1,2,3,4-tetrahydroquinolin-6-yl)benzoate
  参考文献：
  名称：

  The Discovery of I-BET726 (GSK1324726A), a Potent Tetrahydroquinoline ApoA1 Up-Regulator and Selective BET Bromodomain Inhibitor

  摘要：

  Through their function as epigenetic readers of the histone code, the BET family of bromodomain-containing proteins regulate expression of multiple genes of therapeutic relevance, including those involved in tumor cell growth and inflammation. BET bromodomain inhibitors have profound antiproliferative and anti-inflammatory effects which. translate into efficacy in oncology and inflammation models, and the first compounds have now progressed into clinical trials. The exciting biology of the BETs has led to great interest in the discovery of novel inhibitor classes. Here we describe the identification of a novel tetrahydroquinoline series through up-regulation of apoliproprotein A1 and the optimization into potent compounds active in murine models of septic shock and neuroblastoma. At the molecular level, these effects are produced by inhibiton of BET bromodomains X-rays crystallography reveals the interactions explaining the structure-activity relationships of binding. The resulting lead molecule, I-BET726, represents a new, potent, and selective class of tetrahydroquinoline-based BET inhibitors.

  DOI：

  10.1021/jm5010539