2-(1-(4-fluorobenzyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)-4-methyl-N-((6-(trifluoromethyl)pyridin-3-yl)methyl)-thiazole-5-carboxamide | 1184956-89-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(1-(4-fluorobenzyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)-4-methyl-N-((6-(trifluoromethyl)pyridin-3-yl)methyl)-thiazole-5-carboxamide
• 英文别名: 2-(1-(4-fluorobenzyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)-4-methyl-N-((6-(trifluoromethyl)pyridin-3-yl)methyl)thiazole-5-carboxamide；2-[1-[(4-fluorophenyl)methyl]-5-oxo-1,2,4-triazol-4-yl]-4-methyl-N-[[6-(trifluoromethyl)pyridin-3-yl]methyl]-1,3-thiazole-5-carboxamide
• CAS: 1184956-89-5
• 化学式: C₂₁H₁₆F₄N₆O₂S
• 分子量: 492.457
• InChiKey: HHQJIAYZCIQNQF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  119
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2-氨基-4-甲基噻唑-5-甲酸乙酯 在 吡啶 、 potassium carbonate 、 1-羟基苯并三唑 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 对甲苯磺酸 、 一水合肼 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 水 、 丙酮 为溶剂， 反应 29.42h， 生成 2-(1-(4-fluorobenzyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)-4-methyl-N-((6-(trifluoromethyl)pyridin-3-yl)methyl)-thiazole-5-carboxamide
  参考文献：
  名称：

  Discovery of triazolone derivatives as novel, potent stearoyl-CoA desaturase-1 (SCD1) inhibitors

  摘要：

  Stearoyl-CoA desaturase-1 (SCD1) plays an important role in lipid metabolism. Inhibition of SCD1 activity represents a potential novel approach for the treatment of metabolic diseases such as obesity, type 2 diabetes and dyslipidemia, as well as skin diseases, acne and cancer. Herein, we report the synthesis and structure-activity relationships (SAR) of a series of novel triazolone derivatives, culminating in the identification of pyrazolyltriazolone 17a, a potent SCD1 inhibitor, which reduced plasma C16:1/C16:0 triglycerides desaturation index (DI) in an acute Lewis rat model in a dose dependent manner, with an ED50 of 4.6 mg/kg. In preliminary safety studies, compound 17a did not demonstrate adverse effects related to SCD1 inhibition after repeat dosing at 100 mg/kg. Together, these data suggest that sufficient safety margins can be achieved with certain SCD1 inhibitors, thus allowing exploration of clinical utility in metabolic disease settings. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.12.014

文献信息

• Organic compounds
  申请人：Chowdhury Sultan

  公开号：US20090264444A1

  公开（公告）日：2009-10-22

  The present invention provides heterocyclic derivatives that modulate the activity of stearoyl-CoA desaturase. Methods of using such derivatives to modulate the activity of stearoyl-CoA desaturase and pharmaceutical compositions comprising such derivatives are also encompassed.

  本发明提供了调节硬脂酰辅酶A去饱和酶活性的杂环衍生物。本发明还涵盖了使用这些衍生物来调节硬脂酰辅酶A去饱和酶活性的方法和包含这些衍生物的制药组合物。
• ORGANIC COMPOUNDS
  申请人：Chowdhury Sultan

  公开号：US20120014906A1

  公开（公告）日：2012-01-19

  The present invention provides heterocyclic derivatives that modulate the activity of stearoyl-CoA desaturase. Methods of using such derivatives to modulate the activity of stearoyl-CoA desaturase and pharmaceutical compositions comprising such derivatives are also encompassed.

  本发明提供了可以调节硬脂酰辅酶A去饱和酶活性的杂环衍生物。还包括使用这些衍生物来调节硬脂酰辅酶A去饱和酶活性的方法和包含这些衍生物的药物组合物。
• US8049016B2
  申请人：——

  公开号：US8049016B2

  公开（公告）日：2011-11-01
• US8318949B2
  申请人：——

  公开号：US8318949B2

  公开（公告）日：2012-11-27
• Discovery of triazolone derivatives as novel, potent stearoyl-CoA desaturase-1 (SCD1) inhibitors
  作者：Shaoyi Sun、Zaihui Zhang、Natalia Pokrovskaia、Sultan Chowdhury、Qi Jia、Elaine Chang、Kuldip Khakh、Rainbow Kwan、David G. McLaren、Chris C. Radomski、Leslie G. Ratkay、Jianmin Fu、Natalie A. Dales、Michael D. Winther

  DOI：10.1016/j.bmc.2014.12.014

  日期：2015.2

  Stearoyl-CoA desaturase-1 (SCD1) plays an important role in lipid metabolism. Inhibition of SCD1 activity represents a potential novel approach for the treatment of metabolic diseases such as obesity, type 2 diabetes and dyslipidemia, as well as skin diseases, acne and cancer. Herein, we report the synthesis and structure-activity relationships (SAR) of a series of novel triazolone derivatives, culminating in the identification of pyrazolyltriazolone 17a, a potent SCD1 inhibitor, which reduced plasma C16:1/C16:0 triglycerides desaturation index (DI) in an acute Lewis rat model in a dose dependent manner, with an ED50 of 4.6 mg/kg. In preliminary safety studies, compound 17a did not demonstrate adverse effects related to SCD1 inhibition after repeat dosing at 100 mg/kg. Together, these data suggest that sufficient safety margins can be achieved with certain SCD1 inhibitors, thus allowing exploration of clinical utility in metabolic disease settings. (C) 2014 Elsevier Ltd. All rights reserved.