1-((2SR,4RS)-2-methyl-4-(phenylamino)-3,4-dihydroquinolin-1(2H)-yl)ethanone | 26343-38-4

• 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-4-(phenylamino)-3,4-dihydroquinolin-1(2H)-yl)ethanone
• 英文别名: (+/-)-cis-4-Anilino-1-acetyl-2-methyl-1,2,3,4-tetrahydrochinolin；1-[(2R,4S)-4-anilino-2-methyl-3,4-dihydro-2H-quinolin-1-yl]ethanone
• CAS: 26343-38-4
• 化学式: C₁₈H₂₀N₂O
• 分子量: 280.37
• InChiKey: NPJVGQHTXJHUEL-DYVFJYSZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  2,3-二氢-2-甲基-4(1h)-喹啉酮 在 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 四氯化钛 作用下， 以 二氯甲烷 为溶剂， 反应 38.0h， 生成 1-((2SR,4RS)-2-methyl-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

• PGD2 receptor antagonists for the treatment of inflammatory diseases
  申请人：Ghosh Shomir

  公开号：US20050256158A1

  公开（公告）日：2005-11-17

  Disclosed herein are compounds represented by Structural Formula (I) and (I-A): Also disclosed is the use of such compounds for inhibiting the G-protein coupled receptor referred to as chemoattractant receptor-homologous molecule expressed on Th2, or simply “CRTH2” for the treatment of inflammatory disorders. The variables in Structural Formula (I) and (I-A) are defined herein.

  本文揭示了由结构式（I）和（I-A）表示的化合物：还披露了利用这些化合物抑制称为Th2表达的G蛋白偶联受体的化学引诱受体同源分子，简称“CRTH2”，用于治疗炎症性疾病。结构式（I）和（I-A）中的变量在此处被定义。
• US7211672B2
  申请人：——

  公开号：US7211672B2

  公开（公告）日：2007-05-01
• US7504508B2
  申请人：——

  公开号：US7504508B2

  公开（公告）日：2009-03-17
• 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.