4-((2S,4R)-1-acetyl-2-methyl-4-(p-tolylamino)-1,2,3,4-tetrahydroquinolin-6-yl)benzoic acid | 1300691-55-7

• 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: 4-((2S,4R)-1-acetyl-2-methyl-4-(p-tolylamino)-1,2,3,4-tetrahydroquinolin-6-yl)benzoic acid
• 英文别名: 4-{-1-acetyl-2-methyl-4-[(4-methylphenyl)amino]-1,2,3,4-tetrahydro-6-quinolinyl}benzoic acid；4-[(2S,4R)-1-acetyl-2-methyl-4-(4-methylanilino)-3,4-dihydro-2H-quinolin-6-yl]benzoic acid
• CAS: 1300691-55-7
• 化学式: C₂₆H₂₆N₂O₃
• 分子量: 414.504
• InChiKey: PXXDOEMDQBOWHE-BXKMTCNYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  69.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 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 、 三氟化硼乙醚 、 copper diacetate 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 8.25h， 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

文献信息

• BIOORTHOGONAL MONOMERS CAPABLE OF DIMERIZING AND TARGETING BROMODOMAINS, AND METHODS OF USING SAME
  申请人：Coferon, Inc.

  公开号：US20140243321A1

  公开（公告）日：2014-08-28

  Described herein are monomers capable of forming a biologically useful multimer when in contact with one, two, three or more other monomers in an aqueous media. In one aspect, such monomers may be capable of binding to another monomer in an aqueous media (e.g. in vivo) to form a multimer, (e.g. a dimer). Contemplated monomers may include a ligand moiety, a linker element, and a connector element that joins the ligand moiety and the linker element. In an aqueous media, such contemplated monomers may join together via each linker element and may thus be capable of modulating one or more biomolecules substantially simultaneously, e.g., modulate two or more binding domains on a protein or on different proteins.

  本文描述了一种单体，当与一个、两个、三个或更多其他单体在水介质中接触时，能够形成生物上有用的多聚体。在一个方面，这样的单体可以在水介质中（例如在体内）与另一个单体结合形成多聚体（例如二聚体）。考虑到的单体可能包括配体基团、连接元素和连接配体基团和连接元素的连接器元素。在水介质中，这些考虑到的单体可以通过每个连接元素连接在一起，因此可以同时调节一个或多个生物分子，例如调节蛋白质或不同蛋白质上的两个或更多结合域。
• BIVALENT BROMODOMAIN LIGANDS, AND METHODS OF USING SAME
  申请人：Coferon, Inc.

  公开号：US20140243322A1

  公开（公告）日：2014-08-28

  Described herein are compounds capable of modulating one or more biomolecules substantially simultaneously, e.g., modulating two or more binding domains (e.g., bromodomains) on a protein or on different proteins.

  本文描述了一些化合物，能够在实质上同时调节一个或多个生物分子，例如，在蛋白质上或不同蛋白质上调节两个或更多结合域（例如溴结构域）。
• 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.