benzyl (6-(4-methoxyphenyl)-1-methyl-4H-benzo[f ][1,2,4]triazolo[4,3-a][1,4]diazepin-4-yl)carbamate | 1300087-09-5

• 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: benzyl (6-(4-methoxyphenyl)-1-methyl-4H-benzo[f ][1,2,4]triazolo[4,3-a][1,4]diazepin-4-yl)carbamate
• 英文别名: phenylmethyl {1-methyl-6-[4-(methyloxy)phenyl]-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl}carbamate；benzyl N-[6-(4-methoxyphenyl)-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]carbamate
• CAS: 1300087-09-5
• 化学式: C₂₆H₂₃N₅O₃
• 分子量: 453.5
• InChiKey: XLWCHJUWBZQWNQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  90.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-(1H-苯并[d][1,2,3]噻唑-1-基)-2-(((苄氧基)羰基)氨基)乙酸 在 劳森试剂 、 4-二甲氨基吡啶 、 ammonium acetate 、 氨 、 一水合肼 、 溶剂黄146 、 1,2-二氯乙烷 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 47.5h， 生成 benzyl (6-(4-methoxyphenyl)-1-methyl-4H-benzo[f ][1,2,4]triazolo[4,3-a][1,4]diazepin-4-yl)carbamate
  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

• 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.