1-methyl-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-amine | 146397-30-0

• 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: 1-methyl-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-amine
• CAS: 146397-30-0
• 化学式: C₁₇H₁₅N₅
• 分子量: 289.34
• InChiKey: DNOFIMKPVZWRJA-UHFFFAOYSA-N

物化性质

• 沸点：
  514.7±60.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  69.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-methyl-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-amine 、 苄磺酰氯 在 吡啶 作用下， 以 乙腈 为溶剂， 反应 2.5h， 以70%的产率得到N-(1-methyl-6-phenyl-4H-benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepin-4-yl)-1-phenylmethanesulfonamide
  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：

  phenylmethyl (1-methyl-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl)carbamate 在 palladium 10% on activated carbon 1,4-环己二烯 作用下， 以 甲醇 为溶剂， 反应 4.0h， 生成 1-methyl-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-amine
  参考文献：
  名称：

  Condensed Azepine Derivatives As Bromodomain Inhibitors

  摘要：

  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。

  公开号：

  US20120202799A1

文献信息

• [EN] CONDENSED AZEPINE DERIVATIVES AS BROMODOMAIN INHIBITORS<br/>[FR] DÉRIVÉS CONDENSÉS D'AZÉPINES CONVENANT COMME INHIBITEURS DU BROMODOMAINE
  申请人：GLAXOSMITHKLINE LLC

  公开号：WO2011054844A1

  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.

  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。
• CONDENSED AZEPINE DERIVATIVES AS BROMODOMAIN INHIBITORS
  申请人：GlaxoSmithKline LLC

  公开号：EP2496581A1

  公开（公告）日：2012-09-12
• Condensed Azepine Derivatives As Bromodomain Inhibitors
  申请人：Crowe Miriam

  公开号：US20120202799A1

  公开（公告）日：2012-08-09

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

  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。
• Discovery of Epigenetic Regulator I-BET762: Lead Optimization to Afford a Clinical Candidate Inhibitor of the BET Bromodomains
  作者：Olivier Mirguet、Romain Gosmini、Jérôme Toum、Catherine A. Clément、Mélanie Barnathan、Jean-Marie Brusq、Jacqueline E. Mordaunt、Richard M. Grimes、Miriam Crowe、Olivier Pineau、Myriam Ajakane、Alain Daugan、Phillip Jeffrey、Leanne Cutler、Andrea C. Haynes、Nicholas N. Smithers、Chun-wa Chung、Paul Bamborough、Iain J. Uings、Antonia Lewis、Jason Witherington、Nigel Parr、Rab K. Prinjha、Edwige Nicodème

  DOI：10.1021/jm401088k

  日期：2013.10.10

  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.