1-(5-(3,4-dimethoxyphenyl)-1H-benzo[d]imidazol-2-yl)-3-ethylurea | 1438897-49-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-(5-(3,4-dimethoxyphenyl)-1H-benzo[d]imidazol-2-yl)-3-ethylurea
• 英文别名: 1-[6-(3,4-dimethoxyphenyl)-1H-benzimidazol-2-yl]-3-ethylurea
• CAS: 1438897-49-4
• 化学式: C₁₈H₂₀N₄O₃
• 分子量: 340.382
• InChiKey: XQNONYGPUPMLQC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  88.3
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-溴邻苯二胺 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 、 溶剂黄146 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 9.0h， 生成 1-(5-(3,4-dimethoxyphenyl)-1H-benzo[d]imidazol-2-yl)-3-ethylurea
  参考文献：
  名称：

  인돌 유도체 화합물, 이를 포함하는 Ａｂｌ 키나제 저해제 조성물 및 이상세포 성장 질환의 예방 및 치료용 약학 조성물

  摘要：

  本发明涉及苯并咪唑、苯并噻唑和咪唑吡啶衍生物化合物，其用化学式1表示，以及包含这些化合物的Abl激酶抑制剂组合物和用于预防和治疗异常细胞增长疾病的药学组合物。根据本发明，苯并咪唑、苯并噻唑或咪唑吡啶衍生物化合物及其药学上可接受的盐可作为针对Abl激酶的抑制剂，可用于治疗由异常细胞增长、功能或行为引起的疾病，特别是癌症、免疫性疾病、心血管疾病、病毒感染性疾病、炎症性疾病、内分泌疾病和神经性疾病。【化学式1】

  公开号：

  KR101546743B1

文献信息

• 인돌 유도체 화합물, 이를 포함하는 Ａｂｌ 키나제 저해제 조성물 및 이상세포 성장 질환의 예방 및 치료용 약학 조성물
  申请人：Korea Advanced Institute of Science and Technology 한국과학기술원(319980988661) BRN ▼314-82-01980

  公开号：KR101546743B1

  公开（公告）日：2015-08-24

  본 발명은 하기 [화학식 1]로 표시되는 벤즈이미다졸, 벤조싸이아졸 및 이미다조 피리딘 유도체 화합물, 이를 포함하는 Abl 키나제 저해제 조성물 및 이상세포 성장 질환의 예방 및 치료용 약학 조성물에 관한 것으로서, 본 발명에 따른 벤즈이미다졸, 벤조싸이아졸 또는 이미다조피디린 유도체 화합물 및 이의 약학적 수용 가능한 염은 Abl 키나제에 대한 저해제로서 비정상적 세포 성장, 기능 또는 거동으로부터 야기되는 질환, 특히, 암, 면역 질환, 심혈관 질환, 바이러스 감염 질환, 염증성 질환, 내분비 질환 및 신경성 질환을 치료하는데 사용할 수 있다. [화학식 1]

  本发明涉及苯并咪唑、苯并噻唑和咪唑吡啶衍生物化合物，其用化学式1表示，以及包含这些化合物的Abl激酶抑制剂组合物和用于预防和治疗异常细胞增长疾病的药学组合物。根据本发明，苯并咪唑、苯并噻唑或咪唑吡啶衍生物化合物及其药学上可接受的盐可作为针对Abl激酶的抑制剂，可用于治疗由异常细胞增长、功能或行为引起的疾病，特别是癌症、免疫性疾病、心血管疾病、病毒感染性疾病、炎症性疾病、内分泌疾病和神经性疾病。【化学式1】
• Discovery of Picomolar ABL Kinase Inhibitors Equipotent for Wild Type and T315I Mutant via Structure-Based de Novo Design
  作者：Hwangseo Park、Seunghee Hong、Jinhee Kim、Sungwoo Hong

  DOI：10.1021/ja311756u

  日期：2013.6.5

  Although the constitutively activated break-point cluster region-Abelson (ABL) tyrosine kinase is known to cause chronic myelogenous leukemia (CML), the prevalence of drug-resistant ABL mutants has made it difficult to develop effective anti-CML drugs. With the aim to identify new lead compounds for anti-CML drugs, we carried out a structure-based de novo design using the scoring function improved by implementing an accurate solvation free energy term. This approach led to the identification of ABL inhibitors equipotent for the wild type and the most drug-resistant T315I mutant of ABL at the picomolar level. Decomposition analysis of the binding free energy showed that a decrease in the desolvation cost for binding in the ATP-binding site could be as important as the strengthening of enzyme-inhibitor interaction to enhance the potency of an ABL inhibitor with structural modifications. A similar energetic feature was also observed in free energy perturbation (FEP) calculations. Consistent with the previous experimental and computational studies, the hydrogen bond interactions with the backbone groups of Met318 proved to be the most significant binding forces to stabilize the inhibitors in the ATP-binding sites of the wild type and T315I mutant. The results of molecular dynamics simulations indicated that the dynamic stabilities of the hydrogen bonds between the inhibitors and Met318 should also be considered in designing the potent common inhibitors of the wild-type and T315I mutant of ABL.