5-氨基-6-溴-1,3-二甲基-1,3-二氢-苯并咪唑-2-酮 | 24786-52-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 中文名称: 5-氨基-6-溴-1,3-二甲基-1,3-二氢-苯并咪唑-2-酮
• 中文别名: 5-氨基-6-溴-1,3-二甲基-1H-苯并[D]咪唑-2(3H)-酮
• 英文名称: 5-amino-6-bromo-1,3-dimethyl-1,3-dihydro-2H-benzimidazol-2-one
• 英文别名: 5-amino-6-bromo-1,3-dimethyl-1H-benzo[d]imidazol-2(3H)-one；5-amino-6-bromo-1,3-dimethyl-1,3-dihydro-benzoimidazol-2-one；5-Amino-6-brom-1,3-dimethyl-benzimidazol-2-on；5-amino-6-bromo-1,3-dimethylbenzimidazol-2-one
• CAS: 24786-52-5
• 化学式: C₉H₁₀BrN₃O
• mdl: MFCD06618584
• 分子量: 256.102
• InChiKey: SXPRALARBJCCIH-UHFFFAOYSA-N

物化性质

• 沸点：
  384.6±35.0 °C(Predicted)
• 密度：
  1.645±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.222
• 拓扑面积：
  49.6
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  5-氨基-6-溴-1,3-二甲基-1,3-二氢-苯并咪唑-2-酮 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium carbonate 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 26.0h， 生成 tert-butyl 4-(6-(2-methoxybenzamido)-1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)-5,6-dihydropyridine-1(2H)-carboxylate
  参考文献：
  名称：

  GSK6853, a Chemical Probe for Inhibition of the BRPF1 Bromodomain

  摘要：

  The BRPF (Bromodomain and PHD Finger-containing) protein family are important scaffolding proteins for assembly of MYST histone acetyltransferase complexes. A selective benzimidazolone BRPF1 inhibitor showing micro molar activity in a cellular target engagement assay was recently described. Herein, we report the optimization of this series leading to the identification of a superior BRPF1 inhibitor suitable for in vivo studies.

  DOI：

  10.1021/acsmedchemlett.6b00092
• 作为产物：
  描述：

  5-氨基-1,3-二甲基-1,3-二氢-2H-苯并咪唑-2-酮 在 溴 、 溶剂黄146 作用下， 以 氯仿 为溶剂， 反应 0.5h， 以69%的产率得到5-氨基-6-溴-1,3-二甲基-1,3-二氢-苯并咪唑-2-酮
  参考文献：
  名称：

  BROMODOMAIN INHIBITORS FOR TREATING DISEASE

  摘要：

  本文披露了一种在治疗溴结构域含蛋白介导的疾病（如癌症）中有用的化合物和组合物，其具有Formula I的结构： 还提供了一种抑制人类或动物主体中溴结构域含蛋白活性的方法。

  公开号：

  US20160060260A1

文献信息

• Structure-Guided Design of IACS-9571, a Selective High-Affinity Dual TRIM24-BRPF1 Bromodomain Inhibitor
  作者：Wylie S. Palmer、Guillaume Poncet-Montange、Gang Liu、Alessia Petrocchi、Naphtali Reyna、Govindan Subramanian、Jay Theroff、Anne Yau、Maria Kost-Alimova、Jennifer P. Bardenhagen、Elisabetta Leo、Hannah E. Shepard、Trang N. Tieu、Xi Shi、Yanai Zhan、Shuping Zhao、Michelle C. Barton、Giulio Draetta、Carlo Toniatti、Philip Jones、Mary Geck Do、Jannik N. Andersen

  DOI：10.1021/acs.jmedchem.5b00405

  日期：2016.2.25

  The bromodomain containing proteins TRIM24 (tripartite motif containing protein 24) and BRPF1 (bromodomain and PHD finger containing protein 1) are involved in the epigenetic regulation of gene expression and have been implicated in human cancer. Overexpression of TRIM24 correlates with poor patient prognosis, and BRPF1 is a scaffolding protein required for the assembly of histone acetyltransferase complexes, where the gene of MOZ (monocytic leukemia zinc finger protein) was first identified as a recurrent fusion partner in leukemia patients (8p11 chromosomal rearrangements). Here, we present the structure guided development of a series of N,N-dimethyl-benzimidazolone bromodomain inhibitors through the iterative use of X-ray cocrystal structures. A unique binding mode enabled the design of a potent and selective inhibitor 8i (IACS-9571) with low nanomolar affinities for TRIM24 and BRPF1 (ITC K-d = 31 nM and ITC K-d = 14 nM, respectively). With its excellent cellular potency (EC50 = 50 nM) and favorable pharmacokinetic properties (F = 29%), 8i is a high-quality chemical probe for the evaluation of TRIM24 and/or BRPF1 bromodomain function in vitro and in vivo.
• Benzoisoquinolinediones as Potent and Selective Inhibitors of BRPF2 and TAF1/TAF1L Bromodomains
  作者：Léa Bouché、Clara D. Christ、Stephan Siegel、Amaury E. Fernández-Montalván、Simon J. Holton、Oleg Fedorov、Antonius ter Laak、Tatsuo Sugawara、Detlef Stöckigt、Cynthia Tallant、James Bennett、Octovia Monteiro、Laura Díaz-Sáez、Paulina Siejka、Julia Meier、Vera Pütter、Jörg Weiske、Susanne Müller、Kilian V. M. Huber、Ingo V. Hartung、Bernard Haendler

  DOI：10.1021/acs.jmedchem.7b00306

  日期：2017.5.11

  Bromodomains (BD) are readers of lysine acetylation marks present in numerous proteins associated with chromatin. Here we describe a dual inhibitor of the bromodomain and PHD finger (BRPF) family member BRPF2 and the TATA box binding protein-associated factors TAF1 and TAF1L. These proteins are found in large chromatin complexes and play important roles in transcription regulation. The substituted benzoisoquinolinedione series was identified by high-throughput screening, and subsequent structure-activity relationship optimization allowed generation of low nanomolar BRPF2 BD inhibitors with strong selectivity against BRPF1 and BRPF3 BDs. In addition, a strong inhibition of TAF1/TAF1L BD2 was measured for most derivatives. The best compound of the series was BAY-299, which is a very potent, dual inhibitor with an IC50 of 67 nM for BRPF2 BD, 8 nM for TAF1 BD2, and 106 nM for TAF1L BD2. Importantly, no activity was measured for BRD4 BDs. Furthermore, cellular activity was evidenced using a BRPF2- or TAF1-histone H3.3 or H4 interaction assay.
• [EN] BROMODOMAIN INHIBITORS FOR TREATING DISEASE<br/>[FR] INHIBITEURS DE BROMODOMAINE POUR LE TRAITEMENT DE MALADIES
  申请人：UNIV TEXAS

  公开号：WO2016033416A1

  公开（公告）日：2016-03-03

  Disclosed herein are compounds and compositions useful in the treatment of bromodomain-containing protein-mediated diseases, such as cancer, having the structure of Formula I: Methods of inhibiting activity of a bromodomain-containing protein in a human or animal subject are also provided.
• BROMODOMAIN INHIBITORS FOR TREATING DISEASE
  申请人：Board of Regents, The University of Texas System

  公开号：US20160060260A1

  公开（公告）日：2016-03-03

  Disclosed herein are compounds and compositions useful in the treatment of bromodomain-containing protein-mediated diseases, such as cancer, having the structure of Formula I: Methods of inhibiting activity of a bromodomain-containing protein in a human or animal subject are also provided.

  本文披露了一种在治疗溴结构域含蛋白介导的疾病（如癌症）中有用的化合物和组合物，其具有Formula I的结构： 还提供了一种抑制人类或动物主体中溴结构域含蛋白活性的方法。
• GSK6853, a Chemical Probe for Inhibition of the BRPF1 Bromodomain
  作者：Paul Bamborough、Heather A. Barnett、Isabelle Becher、Mark J. Bird、Chun-wa Chung、Peter D. Craggs、Emmanuel H. Demont、Hawa Diallo、David J. Fallon、Laurie J. Gordon、Paola Grandi、Clare I. Hobbs、Edward Hooper-Greenhill、Emma J. Jones、Robert P. Law、Armelle Le Gall、David Lugo、Anne-Marie Michon、Darren J. Mitchell、Rab K. Prinjha、Robert J. Sheppard、Allan J. B. Watson、Robert J. Watson

  DOI：10.1021/acsmedchemlett.6b00092

  日期：2016.6.9

  The BRPF (Bromodomain and PHD Finger-containing) protein family are important scaffolding proteins for assembly of MYST histone acetyltransferase complexes. A selective benzimidazolone BRPF1 inhibitor showing micro molar activity in a cellular target engagement assay was recently described. Herein, we report the optimization of this series leading to the identification of a superior BRPF1 inhibitor suitable for in vivo studies.