2-(1H-benzoimidazol-5-yl)-N-(5-cyclobutyl-thiazol-2-yl)-acetamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 2-(1H-benzoimidazol-5-yl)-N-(5-cyclobutyl-thiazol-2-yl)-acetamide
• 英文别名: 2-(3H-benzimidazol-5-yl)-N-(5-cyclobutyl-1,3-thiazol-2-yl)acetamide
• 化学式: C₁₆H₁₆N₄OS
• 分子量: 312.395
• InChiKey: ADBUMAAMWCLEEI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  98.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-(2-Amino-thiazol-5-yl)-cyclobutanol 在 三乙基硅烷 、 propylphosphonic anhydride 、 三乙胺 、 三氟乙酸 作用下， 以 乙酸乙酯 为溶剂， 反应 2.0h， 生成 2-(1H-benzoimidazol-5-yl)-N-(5-cyclobutyl-thiazol-2-yl)-acetamide
  参考文献：
  名称：

  Discovery and SAR of 2-aminothiazole inhibitors of cyclin-dependent kinase 5/p25 as a potential treatment for Alzheimer’s disease

  摘要：

  High-throughput screening with cyclin-dependent kinase 5 (cdk5)/p25 led to the discovery of N-(5-isopropyl-thiazol-2-yl)isobutyramide (1). This compound is an equipotent inhibitor of cdk5 and cyclin-dependent kinase 2 (cdk2)/cyclin E (IC50 = ca. 320nM). Parallel and directed synthesis techniques were utilized to explore the SAR of this series. Up to 60-fold improvements in potency at cdk5 and 12-fold selectivity over cdk2 were achieved. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.09.006

文献信息

• Thiazole derivatives
  申请人：Pfizer Inc.

  公开号：US20030078252A1

  公开（公告）日：2003-04-24

  The invention provides compounds of formula 1 1 wherein R 1 , R 3 , and R 4 are as defined, and their pharmaceutically acceptable salts. Compounds of formula 1 are indicated to have activity inhibiting cdk5, cdk2, and GSK-3. Pharmaceutical compositions and methods comprising compounds of formula 1 for treating diseases and conditions comprising abnormal cell growth, such as cancer, and neurodegenerative diseases and conditions and those affected by dopamine neurotransmission are described. Also described are pharmaceutical compositions and methods comprising compounds of formula 1 for treating male fertility and sperm motility; diabetes mellitus; impaired glucose tolerance; metabolic syndrome or syndrome X; polycystic ovary syndrome; adipogenesis and obesity; myogenesis and frailty, for example age-related decline in physical performance; acute sarcopenia, for example muscle atrophy and/or cachexia associated with burns, bed rest, limb immobilization, or major thoracic, abdominal, and/or orthopedic surgery; sepsis; hair loss, hair thinning, and balding; and immunodeficiency.

  该发明提供了具有11式的化合物，其中R1、R3和R4如所定义，并其药学上可接受的盐。据指出，11式化合物具有抑制cdk5、cdk2和GSK-3活性的作用。描述了包括11式化合物的药物组合物和方法，用于治疗包括异常细胞增长在内的疾病和病况，如癌症、神经退行性疾病以及受多巴胺神经传导影响的疾病和病况。还描述了包括11式化合物的药物组合物和方法，用于治疗男性生育能力和精子活动性；糖尿病；糖耐量受损；代谢综合征或X综合征；多囊卵巢综合征；脂肪生成和肥胖；肌肉生成和脆弱性，例如与年龄相关的身体表现下降；急性肌肉萎缩，例如与烧伤、卧床、肢体固定或主要胸部、腹部和/或骨科手术相关的肌肉萎缩和/或虚弱；败血症；脱发、头发变薄和秃头；以及免疫缺陷。
• Thiazole derivatives and their use as cdk inhibitors
  申请人：Pfizer Products Inc.

  公开号：EP1256578B1

  公开（公告）日：2006-01-11
• US6720427B2
  申请人：——

  公开号：US6720427B2

  公开（公告）日：2004-04-13
• Discovery and SAR of 2-aminothiazole inhibitors of cyclin-dependent kinase 5/p25 as a potential treatment for Alzheimer’s disease
  作者：Christopher J. Helal、Mark A. Sanner、Christopher B. Cooper、Thomas Gant、Mavis Adam、John C. Lucas、Zhijun Kang、Stanley Kupchinsky、Michael K. Ahlijanian、Bonnie Tate、Frank S. Menniti、Kristin Kelly、Marcia Peterson

  DOI：10.1016/j.bmcl.2004.09.006

  日期：2004.11

  High-throughput screening with cyclin-dependent kinase 5 (cdk5)/p25 led to the discovery of N-(5-isopropyl-thiazol-2-yl)isobutyramide (1). This compound is an equipotent inhibitor of cdk5 and cyclin-dependent kinase 2 (cdk2)/cyclin E (IC50 = ca. 320nM). Parallel and directed synthesis techniques were utilized to explore the SAR of this series. Up to 60-fold improvements in potency at cdk5 and 12-fold selectivity over cdk2 were achieved. (C) 2004 Elsevier Ltd. All rights reserved.