1-((2SR,4RS)-2-methyl-6-phenyl-4-(phenylamino)-3,4-dihydroquinolin-1(2H)-yl)ethanone

• 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: 1-((2SR,4RS)-2-methyl-6-phenyl-4-(phenylamino)-3,4-dihydroquinolin-1(2H)-yl)ethanone
• 英文别名: 1-[(2S,4R)-4-anilino-2-methyl-6-phenyl-3,4-dihydro-2H-quinolin-1-yl]ethanone
• 化学式: C₂₄H₂₄N₂O
• 分子量: 356.467
• InChiKey: HXJWEYPXEZZATP-GAJHUEQPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-((2SR,4RS)-2-methyl-6-phenyl-4-(phenylamino)-3,4-dihydroquinolin-1(2H)-yl)ethanone 、 乙醛 在 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 1,2-二氯乙烷 为溶剂， 以82%的产率得到1-acetyl-N-ethyl-2-methyl-N,6-diphenyl-1,2,3,4-tetrahydro-4-quinolinamine
  参考文献：
  名称：

  [EN] THETRAHYDROQUINOLINES DERIVATIVES AS BROMODOMAIN INHIBITORS
  [FR] DÉRIVÉS DE TÉTRAHYDROQUINOLINES CONVENANT COMME INHIBITEURS DU BROMODOMAINE

  摘要：

  公式（I）的四氢喹啉化合物或其盐，含有这种化合物的药物组合物及其在治疗中的应用，特别是在溴结构域抑制剂适用于治疗的疾病或症状。

  公开号：

  WO2011054848A1
• 作为产物：
  描述：

  N-(1-(1H-benzo[d][1,2,3]triazol-1-yl)ethyl)-4-bromoaniline 在 吡啶 、 盐酸 、 四(三苯基膦)钯 、 三氟化硼乙醚 、 copper diacetate 、 sodium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 二氯甲烷 、 水 为溶剂， 反应 7.25h， 生成 1-((2SR,4RS)-2-methyl-6-phenyl-4-(phenylamino)-3,4-dihydroquinolin-1(2H)-yl)ethanone
  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

文献信息

• [EN] THETRAHYDROQUINOLINES DERIVATIVES AS BROMODOMAIN INHIBITORS<br/>[FR] DÉRIVÉS DE TÉTRAHYDROQUINOLINES CONVENANT COMME INHIBITEURS DU BROMODOMAINE
  申请人：GLAXOSMITHKLINE LLC

  公开号：WO2011054848A1

  公开（公告）日：2011-05-12

  Tetrahydroquinoline compounds of formula (I) or a salt thereof, pharmaceutical compositions containing such compounds and their use in therapy, in particular in the treatment of diseases or conditions for which a bromodomain inhibitor is indicated.

  公式（I）的四氢喹啉化合物或其盐，含有这种化合物的药物组合物及其在治疗中的应用，特别是在溴结构域抑制剂适用于治疗的疾病或症状。
• The Discovery of I-BET726 (GSK1324726A), a Potent Tetrahydroquinoline ApoA1 Up-Regulator and Selective BET Bromodomain Inhibitor
  作者：Romain Gosmini、Van Loc Nguyen、Jérôme Toum、Christophe Simon、Jean-Marie G. Brusq、Gael Krysa、Olivier Mirguet、Alizon M. Riou-Eymard、Eric V. Boursier、Lionel Trottet、Paul Bamborough、Hugh Clark、Chun-wa Chung、Leanne Cutler、Emmanuel H. Demont、Rejbinder Kaur、Antonia J. Lewis、Mark B. Schilling、Peter E. Soden、Simon Taylor、Ann L. Walker、Matthew D. Walker、Rab K. Prinjha、Edwige Nicodème

  DOI：10.1021/jm5010539

  日期：2014.10.9

  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.