N-(3-methylbutyl)-2-[4-[2-(trifluoromethyl)benzoyl]piperazin-1-yl]pyrimidine-5-carboxamide | 842170-25-6

• 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: N-(3-methylbutyl)-2-[4-[2-(trifluoromethyl)benzoyl]piperazin-1-yl]pyrimidine-5-carboxamide
• CAS: 842170-25-6
• 化学式: C₂₂H₂₆F₃N₅O₂
• 分子量: 449.476
• InChiKey: DAXBFBDXGVPOQZ-UHFFFAOYSA-N

物化性质

• 密度：
  1.260±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 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-甲砜基-5-嘧啶甲酸乙酯 在 lithium hydroxide monohydrate 、 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 、 三氟乙酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 反应 58.0h， 生成 N-(3-methylbutyl)-2-[4-[2-(trifluoromethyl)benzoyl]piperazin-1-yl]pyrimidine-5-carboxamide
  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：Xenon Pharmaceuticals Inc.

  公开号：EP2316828A1

  公开（公告）日：2011-05-04

  Compounds for treating an SCD-mediated disease or condition in a mammal, preferably a human, are disclosed, wherein the compounds are of formula (I): where G, J, L, M, x, y, W, V, R2, R3, R4, R5, R6, R7, R8, R8a, R9, R9a, R10, R10a, R11 and R11a are defined herein. Pharmaceutical compositions comprising the compounds of formula (I) are also disclosed.

  本发明公开了用于治疗哺乳动物（最好是人类）SCD 介导的疾病或病症的化合物，其中化合物为式 (I)： 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 在本文中定义。还公开了包含式（I）化合物的药物组合物。
• PIPERAZINE DERIVATIVES AND THEIR USE AS THERAPEUTIC AGENTS
  申请人：Xenon Pharmaceuticals Inc.

  公开号：EP1651620B1

  公开（公告）日：2011-11-09
• COMBINATION THERAPY
  申请人：Xenon Pharmaceuticals Inc.

  公开号：EP1846035B1

  公开（公告）日：2011-09-21
• JP4838128B2
  申请人：——

  公开号：JP4838128B2

  公开（公告）日：2011-12-14
• US7919484B2
  申请人：——

  公开号：US7919484B2

  公开（公告）日：2011-04-05