2-((4S)-6-(3-fluorophenyl)-8-methoxy-1-methyl-4H-benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepin-4-yl)acetic acid | 1300746-63-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: 2-((4S)-6-(3-fluorophenyl)-8-methoxy-1-methyl-4H-benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepin-4-yl)acetic acid
• 英文别名: [(4S)-6-(3-fluorophenyl)-1-methyl-8-(methyloxy)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]acetic acid；2-[(4S)-6-(3-fluorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]acetic acid
• CAS: 1300746-63-7
• 化学式: C₂₀H₁₇FN₄O₃
• 分子量: 380.378
• InChiKey: IESWPCRBAVPPBG-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  28
• 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：
  89.6
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-((4S)-6-(3-fluorophenyl)-8-methoxy-1-methyl-4H-benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepin-4-yl)acetic acid 、 乙胺 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以61%的产率得到N-ethyl-2-((4S)-6-(3-fluorophenyl)-8-methoxy-1-methyl-4H-benzo[f ][1,2,4]triazolo[4,3-a][1,4]diazepin-4-yl)acetamide
  参考文献：
  名称：

  Discovery of Epigenetic Regulator I-BET762: Lead Optimization to Afford a Clinical Candidate Inhibitor of the BET Bromodomains

  摘要：

  The bromo and extra C-terminal domain (BET) family of bromodomains are involved in binding epigenetic marks on histone proteins, more specifically acetylated lysine residues. This paper describes the discovery and structure activity relationships (SAR) of potent benzodiazepine inhibitors that disrupt the function of the BET family of bromodomains (BRD2, BRD3, and BRD4). This work has yielded a potent, selective compound I-BET762 that is now under evaluation in a phase I/II clinical trial for nuclear protein in testis (NUT) midline carcinoma and other cancers.

  DOI：

  10.1021/jm401088k
• 作为产物：
  描述：

  methyl 2-((4S)-6-(3-fluorophenyl)-8-methoxy-1-methyl-4H-benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepin-4-yl)acetate 在 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 生成 2-((4S)-6-(3-fluorophenyl)-8-methoxy-1-methyl-4H-benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepin-4-yl)acetic acid
  参考文献：
  名称：

  Discovery of Epigenetic Regulator I-BET762: Lead Optimization to Afford a Clinical Candidate Inhibitor of the BET Bromodomains

  摘要：

  The bromo and extra C-terminal domain (BET) family of bromodomains are involved in binding epigenetic marks on histone proteins, more specifically acetylated lysine residues. This paper describes the discovery and structure activity relationships (SAR) of potent benzodiazepine inhibitors that disrupt the function of the BET family of bromodomains (BRD2, BRD3, and BRD4). This work has yielded a potent, selective compound I-BET762 that is now under evaluation in a phase I/II clinical trial for nuclear protein in testis (NUT) midline carcinoma and other cancers.

  DOI：

  10.1021/jm401088k

文献信息

• [EN] BENZODIAZEPINE BROMODOMAIN INHIBITOR<br/>[FR] INHIBITEUR DE BROMODOMAINES VIS-À-VIS DE LA BENZODIAZÉPINE
  申请人：GLAXOSMITHKLINE LLC

  公开号：WO2011054845A1

  公开（公告）日：2011-05-12

  Benzodiazepine compounds of formula (I), and salts 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.

  苯二氮卓类化合物的化学式（I）及其盐，含有这类化合物的药物组合物以及它们在治疗中的应用，特别是在治疗溴结构域抑制剂适应症的疾病或症状。
• Benzodiazepine Bromodomain Inhibitor
  申请人：Bailey James

  公开号：US20120252781A1

  公开（公告）日：2012-10-04

  Benzodiazepine compounds of formula (I) and salts thereof, pharmaceutical compositions containing such compounds and their use in therapy.

  公式（I）的苯二氮平化合物及其盐，含有这种化合物的制药组合物以及它们在治疗中的使用。
• BENZODIAZEPINE BROMODOMAIN INHIBITOR
  申请人：GlaxoSmithKline LLC

  公开号：EP2496582B1

  公开（公告）日：2016-01-27
• NOVEL COMPOUNDS
  申请人：GlaxoSmithKline LLC

  公开号：US20170145021A1

  公开（公告）日：2017-05-25

  Benzodiazepine compounds of formula (I) and salts thereof, pharmaceutical compositions containing such compounds and their use in therapy.
• US9102677B2
  申请人：——

  公开号：US9102677B2

  公开（公告）日：2015-08-11