1-(3,4-dimethoxyphenyl)-3-[4-(1H-imidazol-1-yl)butyl]thiourea

• 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-(3,4-dimethoxyphenyl)-3-[4-(1H-imidazol-1-yl)butyl]thiourea
• 英文别名: 1-(3,4-dimethoxyphenyl)-3-(4-imidazol-1-ylbutyl)thiourea
• 化学式: C₁₆H₂₂N₄O₂S
• 分子量: 334.442
• InChiKey: VXLOBFQYXFELEU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  23
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  92.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-(4-(1H-imidazol-1-yl)butyl)isoindoline-1,3-dione 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 10.0h， 生成 1-(3,4-dimethoxyphenyl)-3-[4-(1H-imidazol-1-yl)butyl]thiourea
  参考文献：
  名称：

  The First Potent Inhibitors for Human Glutaminyl Cyclase:  Synthesis and Structure−Activity Relationship

  摘要：

  The first effective inhibitors for human glutaminyl cyclase (QC) are described. The structures are developed by applying a ligand-based optimization approach starting from imidazole. Screening of derivatives of that heterocycle led to compounds of the imidazol-1-yl-alkyl thiourea type as a lead scaffold. A library of thiourea derivatives was synthesized, resulting in an inhibitory improvement by 2 orders of magnitude, leading to 1-(3-(1H-imidazol-1-yl)propyl)-3-(3,4-dimethoxyphenyl)thiourea as a potent inhibitor. Systematic exploitation of the scaffold revealed a strong impact on the inhibitory efficacy and resulted in the development of imidazole-propyl-thioamides as another new class of potent inhibitors. A flexible alignment of the most potent compounds of the thioamide and thiourea class and a QC substrate revealed a good match of characteristic features of the molecules, which suggests a similar binding mode of both inhibitors and the substrate to the active site of QC.

  DOI：

  10.1021/jm050756e

文献信息

• Novel inhibitors of glutaminyl cyclase
  申请人：Schilling Stephan

  公开号：US20050215573A1

  公开（公告）日：2005-09-29

  The present invention relates to novel inhibitors of glutaminyl cyclase and combinations thereof for the treatment of neuronal disorders, especially Alzheimer's disease, Down Syndrome, Parkinson disease, Chorea Huntington, pathogenic psychotic conditions, schizophrenia, impaired food intake, sleep-wakefulness, impaired homeostatic regulation of energy metabolism, impaired autonomic function, impaired hormonal balance, impaired regulation, body fluids, hypertension, fever, sleep dysregulation, anorexia, anxiety related disorders including depression, seizures including epilepsy, drug withdrawal and alcoholism, neurodegenerative disorders including cognitive dysfunction and dementia.

  本发明涉及新型谷氨酰环化酶抑制剂及其组合物，用于治疗神经系统疾病，特别是阿尔茨海默病、唐氏综合征、帕金森病、亨廷顿舞蹈症、致病性精神病症、精神分裂症、食欲受损、睡眠-觉醒、体内能量代谢的失衡、自主神经功能受损、激素平衡受损、调节失调、体液平衡、高血压、发热、睡眠失调、厌食症、焦虑相关疾病包括抑郁症、癫痫发作包括癫痫、药物戒断和酗酒、神经退行性疾病包括认知功能障碍和痴呆症。
• CRYSTAL STRUCTURE OF GLUTAMINYL CYCLASE
  申请人：Probiodrug AG

  公开号：EP2606129B1

  公开（公告）日：2015-03-25
• Novel Inhibitors of Glutaminyl Cyclase
  申请人：Schilling Stephan

  公开号：US20090018087A1

  公开（公告）日：2009-01-15

  The present invention relates to novel inhibitors of glutaminyl cyclase and combinations thereof for the treatment of neuronal disorders, especially Alzheimer's disease, Down Syndrome, Parkinson disease, Chorea Huntington, pathogenic psychotic conditions, schizophrenia, impaired food intake, sleep-wakefulness, impaired homeostatic regulation of energy metabolism, impaired autonomic function, impaired hormonal balance, impaired regulation, body fluids, hypertension, fever, sleep dysregulation, anorexia, anxiety related disorders including depression, seizures including epilepsy, drug withdrawal and alcoholism, neurodegenerative disorders including cognitive dysfunction and dementia.
• US7304086B2
  申请人：——

  公开号：US7304086B2

  公开（公告）日：2007-12-04
• US7897633B2
  申请人：——

  公开号：US7897633B2

  公开（公告）日：2011-03-01