1-(2-((3-chloro-4-methylphenyl)amino)-4-methylthiazol-5-yl)ethanone | 398471-35-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(2-((3-chloro-4-methylphenyl)amino)-4-methylthiazol-5-yl)ethanone
• 英文别名: 1-[2-(3-Chloro-4-methylanilino)-4-methyl-1,3-thiazol-5-yl]ethanone
• CAS: 398471-35-7
• 化学式: C₁₃H₁₃ClN₂OS
• 分子量: 280.778
• InChiKey: SBNXUOFSARYYOV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  70.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-氯-4-甲基异硫氰酸苯酯 在 ammonium hydroxide 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 1-(2-((3-chloro-4-methylphenyl)amino)-4-methylthiazol-5-yl)ethanone
  参考文献：
  名称：

  Design, Synthesis, X-ray Crystallographic Analysis, and Biological Evaluation of Thiazole Derivatives as Potent and Selective Inhibitors of Human Dihydroorotate Dehydrogenase

  摘要：

  Human dihydroorotate dehydrogenase (HsDHODH) is a flavin-dependent mitochondrial enzyme that has been certified as a potential therapeutic target for the treatment of rheumatoid arthritis and other autoimmune diseases. On the basis of lead compound 4, which was previously identified as potential HsDHODH inhibitor, a novel series of thiazole derivatives were designed and synthesized. The X-ray complex structures of the promising analogues 12 and 33 confirmed that these inhibitors bind at the putative ubiquinone binding tunnel and guided us to explore more potent inhibitors, such as compounds 44, 46, and 47 which showed double digit nanomolar activities of 26, 18, and 29 nM, respectively. Moreover, 44 presented considerable anti-inflammation effect in vivo and significantly alleviated foot swelling in a dose-dependent manner, which disclosed that thiazole-scaffold analogues can be developed into the drug candidates for the treatment of rheumatoid arthritis by suppressing the bioactivity of HsDHODH.

  DOI：

  10.1021/jm501127s

文献信息

• NOVEL METHODS FOR TREATING NEURODEGENERATIVE DISEASES
  申请人：GENZYME CORPORATION

  公开号：US20160287549A1

  公开（公告）日：2016-10-06

  The invention relates to dihydroorate dehydrogenase (DHODH) inhibitors useful for the treatment of neurodegenerative diseases, such as amyotrophic lateral sclerosis.