5-(4-(2-(trifluoromethyl)benzoyl)piperazin-1-yl)pyrazine-2-carboxylic acid | 1417790-20-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 5-(4-(2-(trifluoromethyl)benzoyl)piperazin-1-yl)pyrazine-2-carboxylic acid
• 英文别名: 5-[4-[2-(Trifluoromethyl)benzoyl]piperazin-1-yl]pyrazine-2-carboxylic acid
• CAS: 1417790-20-5
• 化学式: C₁₇H₁₅F₃N₄O₃
• 分子量: 380.326
• InChiKey: ZFORSGFNKFPKNL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  86.6
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  异戊胺 、 5-(4-(2-(trifluoromethyl)benzoyl)piperazin-1-yl)pyrazine-2-carboxylic acid 在 1-羟基苯并三唑一水物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 以3.5 mg的产率得到4-(2-trifluoromethyl-benzoyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-5'-carboxylic acid (3-methyl-butyl)-amide
  参考文献：
  名称：

  Discovery of Piperazin-1-ylpyridazine-Based Potent and Selective Stearoyl-CoA Desaturase-1 Inhibitors for the Treatment of Obesity and Metabolic Syndrome

  摘要：

  Stearoyl-CoA desaturase-1 (SCD1) catalyzes de novo synthesis of monounsaturated fatty acids from saturated fatty acids. Studies have demonstrated that rodents lacking a functional SCD1 gene have an improved metabolic profile, including reduced weight gain, lower triglycerides, and improved insulin response. In this study, we discovered a series of piperazinylpyridazine-based highly potent, selective, and orally bioavailable compounds. Particularly, compound 49 (XEN103) was highly active in vitro (mSCD1 IC50 = 14 nM and HepG2 IC50 = 12 nM) and efficacious in vivo (ED50 = 0.8 mg/kg). It also demonstrated striking reduction of weight gain in a rodent model. Our findings with small-molecule SCD1 inhibitors confirm the importance of this target in metabolic regulation, describe novel models for assessing SCD1 inhibitors for efficacy and tolerability and demonstrate an opportunity to develop a novel therapy for metabolic disease.

  DOI：

  10.1021/jm301661h
• 作为产物：
  描述：

  2-三氟甲基苯甲酰氯 在 四丁基碘化铵 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 N,N-二异丙基乙胺 、 三氟乙酸 、 lithium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 109.0h， 生成 5-(4-(2-(trifluoromethyl)benzoyl)piperazin-1-yl)pyrazine-2-carboxylic acid
  参考文献：
  名称：

  Discovery of Piperazin-1-ylpyridazine-Based Potent and Selective Stearoyl-CoA Desaturase-1 Inhibitors for the Treatment of Obesity and Metabolic Syndrome

  摘要：

  Stearoyl-CoA desaturase-1 (SCD1) catalyzes de novo synthesis of monounsaturated fatty acids from saturated fatty acids. Studies have demonstrated that rodents lacking a functional SCD1 gene have an improved metabolic profile, including reduced weight gain, lower triglycerides, and improved insulin response. In this study, we discovered a series of piperazinylpyridazine-based highly potent, selective, and orally bioavailable compounds. Particularly, compound 49 (XEN103) was highly active in vitro (mSCD1 IC50 = 14 nM and HepG2 IC50 = 12 nM) and efficacious in vivo (ED50 = 0.8 mg/kg). It also demonstrated striking reduction of weight gain in a rodent model. Our findings with small-molecule SCD1 inhibitors confirm the importance of this target in metabolic regulation, describe novel models for assessing SCD1 inhibitors for efficacy and tolerability and demonstrate an opportunity to develop a novel therapy for metabolic disease.

  DOI：

  10.1021/jm301661h

文献信息

• PIPERAZINE DERIVATIVES AND THEIR USE AS THERAPEUTIC AGENTS
  申请人：Sviridov Serguei

  公开号：US20090030008A1

  公开（公告）日：2009-01-29

  Methods of treating an SCD-mediated disease or condition in a mammal, preferably a human, are disclosed, wherein the methods comprise administering to a mammal in need thereof a compound of formula (I): where G, J, L, M, x, y, W, V, R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 8a , R 9 , R 9a , R 10 , R 10a , R 11 and R 11a are defined herein. Pharmaceutical compositions comprising the compounds of formula (I) are also disclosed.

  本发明揭示了治疗哺乳动物（优选为人类）SCD介导的疾病或病状的方法，其中该方法包括向需要该方法的哺乳动物施用公式（I）的化合物：其中，G、J、L、M、x、y、W、V、R2、R3、R4、R5、R6、R7、R8、R8a、R9、R9a、R10、R10a、R11和R11a在此定义。本发明还揭示了包含公式（I）的化合物的制药组合物。
• Piperazine derivatives and their use as therapeutic agents
  申请人：Sviridov Serguei

  公开号：US20060252767A1

  公开（公告）日：2006-11-09

  Methods of treating an SCD-mediated disease or condition in a mammal, preferably a human, are disclosed, wherein the methods comprise administering to a mammal in need thereof a compound of formula (I): where G, J, L, M, x, y, W, V, R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 8a , R 9 , R 9a , R 10 , R 10a , R 11 and R 11a are defined herein. Pharmaceutical compositions comprising the compounds of formula (I) are also disclosed.

  本发明公开了治疗哺乳动物，尤其是人类SCD介导的疾病或病症的方法，其中所述方法包括向需要治疗的哺乳动物中给予式(I)的化合物，其中G、J、L、M、x、y、W、V、R2、R3、R4、R5、R6、R7、R8、R8a、R9、R9a、R10、R10a、R11和R11a在此被定义。本发明还公开了包含式(I)化合物的药物组合物。
• COMBINATION THERAPY
  申请人：XENON PHARMACEUTICALS INC.

  公开号：EP1846035A2

  公开（公告）日：2007-10-24
• JP2007500720A
  申请人：——

  公开号：JP2007500720A

  公开（公告）日：2007-01-18
• Therapeutic methods, compounds and compositions
  申请人：Bartel L. Paul

  公开号：US20070087363A1

  公开（公告）日：2007-04-19

  The invention provides methods of treating, preventing, delaying the onset, slowing the progression, or reversing the symptoms of Alzheimer's disease and other neurodegenerative diseases characterized by the accumulation of amyloid plaques comprising the Aβ42 peptide. The invention also provides compounds that reduce the production or secretion of the Aβ42-peptide by cells, and pharmaceutical compositions comprising such compounds, for the treatment of neurodegenerative diseases characterized by the accumulation of amyloid plaques comprising the Aβ42 peptide.