5-氨基-6-甲氧基-1,3-二甲基-1,3-二氢-苯并咪唑-2-酮 | 73778-95-7

• 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-甲氧基-1,3-二甲基-1,3-二氢-苯并咪唑-2-酮
• 英文名称: 5-amino-6-methoxy-1,3-dimethyl-1,3-dihydro-2H-benzimidazol-2-one
• 英文别名: 5-Amino-6-methoxy-1,3-dimethyl-1,3-dihydro-benzoimidazol-2-one；5-amino-6-methoxy-1,3-dimethylbenzimidazol-2-one
• CAS: 73778-95-7
• 化学式: C₁₀H₁₃N₃O₂
• mdl: MFCD08056127
• 分子量: 207.232
• InChiKey: FUANRVOPAVWOIK-UHFFFAOYSA-N

物化性质

• 沸点：
  379.0±35.0 °C(Predicted)
• 密度：
  1.268±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  58.8
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  5-氨基-6-甲氧基-1,3-二甲基-1,3-二氢-苯并咪唑-2-酮 、 2,3-二氯苯磺酰氯 在 吡啶 作用下， 反应 1.0h， 以20 mg的产率得到2,3-dichloro-N-(6-methoxy-1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)benzenesulfonamide
  参考文献：
  名称：

  Lead identification of benzimidazolone and azabenzimidazolone arylsulfonamides as CC-chemokine receptor 4 (CCR4) antagonists

  摘要：

  A knowledge-based library of 2,3-dichlorophenylsulfonyl derivatives of commercially available aryl amines was synthesised and screened as human CCR4 antagonists, in order to identify a suitable hit for the start of a lead-optimisation programme. Hits were required to be more potent than an existing indazole series, have better physicochemical properties (clogP <3.5, chrom logD₇.₄ <5.3 and CLND solubility >116 μg/mL), and be stable to acid and light. The benzimidazol-2-one core was identified as a hit suitable for further investigation. Substitution at N1 with small alkyl groups was tolerated; however, these analogues were inactive in the whole blood assay (pA₂ <5). Azabenzimidazolone analogues were all found to be active, with compound 38 exhibiting whole blood activity of 6.1, low molecular weight (389) and chrom logD₇.₄ (2.4), high LE (0.43), and solubility (152 μg/mL). In addition, 38 had human serum albumin binding of around 93% and met all the criteria for progression to lead optimisation.

  DOI：

  10.1016/j.bmc.2014.05.021
• 作为产物：
  描述：

  5-methoxy-1,3-dimethyl-6-nitro-1H-benzo[d]imidazol-2(3H)-one 在 10% Pd/C 、 氢气 作用下， 以 乙醇 、 乙酸乙酯 为溶剂， 反应 18.0h， 生成 5-氨基-6-甲氧基-1,3-二甲基-1,3-二氢-苯并咪唑-2-酮
  参考文献：
  名称：

  Lead identification of benzimidazolone and azabenzimidazolone arylsulfonamides as CC-chemokine receptor 4 (CCR4) antagonists

  摘要：

  A knowledge-based library of 2,3-dichlorophenylsulfonyl derivatives of commercially available aryl amines was synthesised and screened as human CCR4 antagonists, in order to identify a suitable hit for the start of a lead-optimisation programme. Hits were required to be more potent than an existing indazole series, have better physicochemical properties (clogP <3.5, chrom logD₇.₄ <5.3 and CLND solubility >116 μg/mL), and be stable to acid and light. The benzimidazol-2-one core was identified as a hit suitable for further investigation. Substitution at N1 with small alkyl groups was tolerated; however, these analogues were inactive in the whole blood assay (pA₂ <5). Azabenzimidazolone analogues were all found to be active, with compound 38 exhibiting whole blood activity of 6.1, low molecular weight (389) and chrom logD₇.₄ (2.4), high LE (0.43), and solubility (152 μg/mL). In addition, 38 had human serum albumin binding of around 93% and met all the criteria for progression to lead optimisation.

  DOI：

  10.1016/j.bmc.2014.05.021

文献信息

• 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.
• Lead identification of benzimidazolone and azabenzimidazolone arylsulfonamides as CC-chemokine receptor 4 (CCR4) antagonists
  作者：Afjal H. Miah、Hossay Abas、Malcolm Begg、Benjamin J. Marsh、Daniel E. O’Flynn、Alison J. Ford、Jonathan M. Percy、Panayiotis A. Procopiou、Steve A. Richards、Sally-Anne Rumley

  DOI：10.1016/j.bmc.2014.05.021

  日期：2014.8

  A knowledge-based library of 2,3-dichlorophenylsulfonyl derivatives of commercially available aryl amines was synthesised and screened as human CCR4 antagonists, in order to identify a suitable hit for the start of a lead-optimisation programme. Hits were required to be more potent than an existing indazole series, have better physicochemical properties (clogP <3.5, chrom logD₇.₄ <5.3 and CLND solubility >116 μg/mL), and be stable to acid and light. The benzimidazol-2-one core was identified as a hit suitable for further investigation. Substitution at N1 with small alkyl groups was tolerated; however, these analogues were inactive in the whole blood assay (pA₂ <5). Azabenzimidazolone analogues were all found to be active, with compound 38 exhibiting whole blood activity of 6.1, low molecular weight (389) and chrom logD₇.₄ (2.4), high LE (0.43), and solubility (152 μg/mL). In addition, 38 had human serum albumin binding of around 93% and met all the criteria for progression to lead optimisation.