4-amino-3-(1H-benzo[d]imidazol-2-yl)quinolin-2(1H)-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 4-amino-3-(1H-benzo[d]imidazol-2-yl)quinolin-2(1H)-one
• 英文别名: 4-amino-3-(1H-benzimidazol-2-yl)quinolin-2(1H)-one；4-amino-3-(1H-benzimidazol-2-yl)-1H-quinolin-2-one
• 化学式: C₁₆H₁₂N₄O
• 分子量: 276.297
• InChiKey: SQUBJXXBYMPOFW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  83.8
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-(1H-1,3-苯并咪唑-2-基)乙酸乙酯 、 2-氨基苯甲腈 在 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 以48%的产率得到4-amino-3-(1H-benzo[d]imidazol-2-yl)quinolin-2(1H)-one
  参考文献：
  名称：

  Design, Structure−Activity Relationships and in Vivo Characterization of 4-Amino-3-benzimidazol-2-ylhydroquinolin-2-ones: A Novel Class of Receptor Tyrosine Kinase Inhibitors

  摘要：

  The inhibition of key receptor tyrosine kinases (RTKs) that are implicated in tumor vasculature formation and maintenance, as well as tumor progression and metastasis, has been a major focus in oncology research over the last several years. Many potent small molecule inhibitors of vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) kinases have been evaluated. More recently, compounds that act through the complex inhibition of multiple kinase targets have been reported and may exhibit improved clinical efficacy. We report herein a series of potent, orally efficacious 4-amino3-benzimidazol-2-ylhydroquinolin-2-one analogues as inhibitors of VEGF, PDGF, and fibroblast growth factor (FGF) receptor tyrosine kinases. Compounds in this class, such as 5 (TK1258), are reversible ATP-competitive inhibitors of VEGFR-2, FGFR-1, and PDGFR beta with IC50 values <0.1 mu M. On the basis of its favorable in vitro and in vivo properties, compound 5 was selected for clinical evaluation and is currently in phase I clinical trials.

  DOI：

  10.1021/jm800790t

文献信息

• Combination therapy with CHK1 inhibitors
  申请人：Gesner G. Thomas

  公开号：US20050256157A1

  公开（公告）日：2005-11-17

  Compounds of Structure I, and salts, tautomers, stereoisomers, and mixtures thereof may be used in methods of inhibiting checkpoint kinase 1 in subjects, in methods for inducing cell cycle progression, and in methods for increasing apoptosis in cells. Such compounds may be used to prepare pharmaceutical compositions and may be used in conjunction with DNA damaging agents.

  结构I的化合物及其盐类、互变异构体、立体异构体和混合物可用于抑制受试者中的检查点激酶1，用于诱导细胞周期进展的方法，以及用于增加细胞凋亡的方法。这些化合物可用于制备药物组合物，并且可以与DNA损伤剂联合使用。
• Inhibition of FGFR3 and treatment of multiple myeloma
  申请人：Cai Shaopei

  公开号：US20050261307A1

  公开（公告）日：2005-11-24

  Methods of inhibiting fibroblast growth factor receptor 3 and treating various conditions mediated by fibroblast growth factor receptor 3 are provided that include administering to a subject a compound of Structure I, a pharmaceutically acceptable salt thereof, a tautomer thereof, or a pharmaceutically acceptable salt of the tautomer. Compounds having the Structure I have the following structure where and have the variables described herein. Such compounds may be used to prepare medicaments for use in inhibiting fibroblast growth factor receptor 3 and for use in treating conditions mediated by fibroblast growth factor receptor 3 such as multiple myeloma.

  提供了抑制成纤维母细胞生长因子受体3并治疗由纤维母细胞生长因子受体3介导的各种疾病的方法，包括向受试者施用结构I的化合物，其药学上可接受的盐，其互变异构体，或其互变异构体的药学上可接受的盐。具有结构I的化合物具有以下结构，其中具有本文描述的变量。这些化合物可用于制备用于抑制纤维母细胞生长因子受体3和用于治疗由纤维母细胞生长因子受体3介导的疾病，如多发性骨髓瘤的药物。
• [EN] TARGETED RNA DEGRADATION ALLOWS PRECISION REPURPOSING OF PROTEIN-TARGETED SMALL MOLECULE MEDICINES TO RNA<br/>[FR] DÉGRADATION D'ARN CIBLÉE PERMETTANT UNE REDÉFINITION DE PRÉCISION DE MÉDICAMENTS À PETITES MOLÉCULES À CIBLAGE PROTÉIQUE POUR L'ARN
  申请人：SCRIPPS RESEARCH INST

  公开号：WO2022026851A1

  公开（公告）日：2022-02-03

  The protein targeted medicine, Dovitinib, has been repurposed to target a non-coding RNA by using selection and computational drug design via Inforna. Selectivity was achieved for pre-miR-21 by endowing the medicine with the ability to recruit RNA quality control enzymes to cleave the target.

  定向靶向蛋白质药物Dovitinib已经通过使用选择和计算药物设计，通过Inforna重新定位，以靶向非编码RNA。通过赋予药物招募RNA质量控制酶来切割目标，已经实现了对pre-miR-21的选择性。
• Modulation of inflammatory and metastatic processes
  申请人：Heise Carla

  公开号：US20050239825A1

  公开（公告）日：2005-10-27

  Methods of using compounds having Structure I or the salts or tautomers of the compounds in the treatment of disorders relating to cell adhesion and metastatic processes are presented herein.

  本文介绍了使用具有结构I的化合物或该化合物的盐或互变异构体来治疗与细胞黏附和转移过程相关的疾病的方法。
• Use of small molecule compounds for immunopotentiation
  申请人：Valiante M. Nicholas

  公开号：US20050136065A1

  公开（公告）日：2005-06-23

  The invention provides immunostimulatory compositions comprising a small molecule immuno-poteniator (SMIP) compound and methods of administration thereof. Also provided are methods of administering a SMIP compound in an effective amount to enhance the immune response of a subject to an antigen. Further provided are novel compositions and methods of administering SMIP compounds alone or in combination with another agent for the treatment of cancer, infectious diseases and/or allergies/asthma.

  本发明提供了包含小分子免疫增强剂（SMIP）化合物的免疫刺激组合物及其给药方法。还提供了在有效剂量下给予SMIP化合物以增强受体对抗原的免疫反应的方法。此外，还提供了用于治疗癌症、传染性疾病和/或过敏/哮喘的新型组合物和给药SMIP化合物的方法，单独或与另一种药物联合使用。