4-{(2S,4R)-1-acetyl-4-[(4-chlorophenyl)amino]-2-methyl-1,2,3,4-tetrahydro-6-quinolinyl}benzamide | 1300694-21-6

• 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: 4-{(2S,4R)-1-acetyl-4-[(4-chlorophenyl)amino]-2-methyl-1,2,3,4-tetrahydro-6-quinolinyl}benzamide
• 英文别名: 4-[(2S,4R)-1-acetyl-4-(4-chloroanilino)-2-methyl-3,4-dihydro-2H-quinolin-6-yl]benzamide
• CAS: 1300694-21-6
• 化学式: C₂₅H₂₄ClN₃O₂
• 分子量: 433.937
• InChiKey: BYXLVMRVUBFJJF-NPMXOYFQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  75.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4-溴苯胺 在 吡啶 、 盐酸 、 三氟化硼乙醚 、 copper diacetate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 36.5h， 生成 4-{(2S,4R)-1-acetyl-4-[(4-chlorophenyl)amino]-2-methyl-1,2,3,4-tetrahydro-6-quinolinyl}benzamide
  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。
• Thetrahydroquinolines Derivatives As Bromodomain Inhibitors
  申请人：Demont Emmanuel Hubert

  公开号：US20120208814A1

  公开（公告）日：2012-08-16

  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 indicted.

  公式（I）的四氢喹啉化合物或其盐，含有这种化合物的制药组合物以及它们在治疗中的应用，特别是在治疗需要溴域抑制剂的疾病或病状方面的应用。
• Thetrahydroquinolines derivatives as bromodomain inhibitors
  申请人：Demont Emmanuel Hubert

  公开号：US08580957B2

  公开（公告）日：2013-11-12

  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 indicted.

  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以及它们在治疗中的应用，特别是在治疗需要溴域抑制剂的疾病或情况中的应用。
• TETRAHYDROQUINOLINES DERIVATIVES AS BROMODOMAIN INHIBITORS
  申请人：GlaxoSmithKline LLC

  公开号：EP2496558B1

  公开（公告）日：2016-03-30
• US8580957B2
  申请人：——

  公开号：US8580957B2

  公开（公告）日：2013-11-12