5-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-pyrimidine-2-carboxylic acid hexylamide

• 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]-pyrimidine-2-carboxylic acid hexylamide
• 英文别名: N-hexyl-5-[4-[2-(trifluoromethyl)benzoyl]piperazin-1-yl]pyrimidine-2-carboxamide
• 化学式: C₂₃H₂₈F₃N₅O₂
• 分子量: 463.503
• InChiKey: OWUBZQNYYJEHEA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  78.4
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-三氟甲基苯甲酰氯 在 tris(triphenylphosphine)ruthenium(II) chloride 、 caesium carbonate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 N-甲基吡咯烷酮 、 乙二醇二甲醚 、 二氯甲烷 、 水 为溶剂， 反应 92.0h， 生成 5-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-pyrimidine-2-carboxylic acid hexylamide
  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
• JP4838128B2
  申请人：——

  公开号：JP4838128B2

  公开（公告）日：2011-12-14