6-[4-(2-trifluoromethylbenzoyl)piperazin-1-yl]pyridazine-3-carboxylic acid (3-hydroxy-3-methylbutyl)amide | 840491-22-7

• 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: 6-[4-(2-trifluoromethylbenzoyl)piperazin-1-yl]pyridazine-3-carboxylic acid (3-hydroxy-3-methylbutyl)amide
• 英文别名: N-(3-hydroxy-3-methylbutyl)-6-[4-[2-(trifluoromethyl)benzoyl]piperazin-1-yl]pyridazine-3-carboxamide
• CAS: 840491-22-7
• 化学式: C₂₂H₂₆F₃N₅O₃
• 分子量: 465.475
• InChiKey: ASQKCXTVHBOYJJ-UHFFFAOYSA-N

物化性质

• 沸点：
  720.6±60.0 °C(Predicted)
• 密度：
  1.316±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  33
• 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：
  98.7
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  6-[4-(2-trifluoromethylbenzoyl)piperazin-1-yl]pyridazine-3-carboxylic acid (3-hydroxy-3-methylbutyl)amide 、 乙酸酐 以the title compound was obtained as a white powder (80% yield)的产率得到acetic acid 1,1-dimethyl-3-({6-[4-(2-trifluoromethylbenzoyl)piperazin-1-yl]-pyridazine-3-carbonyl}amino)propyl ester
  参考文献：
  名称：

  PYRIDAZINE DERIVATIVES AND THEIR USE AS THERAPEUTIC AGENTS

  摘要：

  治疗SCD介导的哺乳动物皮肤疾病或状况的方法，最好是人类，包括向需要治疗的哺乳动物（例如人类）施用式(I)的化合物：其中x、y、W、V、R2、R3、R4、R5、R6、R6a、R7、R7a、R8、R8a、R9和R9a在此定义。

  公开号：

  US20100311763A1
• 作为产物：
  描述：

  2-三氟甲基苯甲酰氯 在 氯化亚砜 、 lithium hydroxide monohydrate 、 四丁基碘化铵 、 potassium carbonate 、 三乙胺 、 N,N-二异丙基乙胺 、 N,N-二甲基甲酰胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 氯仿 、 水 为溶剂， 反应 72.0h， 生成 6-[4-(2-trifluoromethylbenzoyl)piperazin-1-yl]pyridazine-3-carboxylic acid (3-hydroxy-3-methylbutyl)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

文献信息

• PYRIDAZINE DERIVATIVES AND THEIR USE AS THERAPEUTIC AGENTS
  申请人：Bilich Andreas

  公开号：US20080280916A1

  公开（公告）日：2008-11-13

  Methods of treating an SCD-mediated skin disorder or condition in a mammal, preferably a human include administering to a mammal in need thereof a compound of formula (I): where x, y, W, V, R 2 , R 3 , R 4 , R 5 , R 6 , R 6a , R 7 , R 7a , R 8 , R 8a , R 9 and R 9a are defined herein.

  治疗哺乳动物，特别是人类SCD介导的皮肤疾病或症状的方法包括向需要治疗的哺乳动物给予以下式子(I)的化合物：其中x，y，W，V，R2，R3，R4，R5，R6，R6a，R7，R7a，R8，R8a，R9和R9a在此处定义。
• PYRIDAZINE DERIVATIVES AND THEIR USE AS THERAPEUTIC AGENTS IN THE TREATMENT OF SKIN DISORDERS
  申请人：Billich Andreas

  公开号：US20110021530A1

  公开（公告）日：2011-01-27

  Methods of treating an SCD-mediated skin disorder or condition in a mammal, preferably a human, including administering to a mammal in need thereof a compound of formula (I): where x, y, W, V, R 2 , R 3 , R 4 , R 5 , R 6 , R 6a , R 7 , R 7a , R 8 , R 8a , R 9 and R 9a are defined herein, and compositions including a compound of formula (I).

  治疗哺乳动物，尤其是人类SCD介导的皮肤疾病或症状的方法，包括向需要该治疗的哺乳动物施用式(I)的化合物，其中x，y，W，V，R2，R3，R4，R5，R6，R6a，R7，R7a，R8，R8a，R9和R9a在此定义，并包括含有式(I)化合物的组合物。
• Piperazine derivatives and their use as therapeutic agents
  申请人：Xenon Pharmaceuticals Inc.

  公开号：EP2316827A1

  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 x y, W, V, R2, R3, R4, R5, R6, R6a, R7, R7a, R8, R8a, R9 and R9a 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 x y、W、V、R2、R3、R4、R5、R6、R6a、R7、R7a、R8、R8a、R9 和 R9a 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：EP1648874B1

  公开（公告）日：2011-10-05
• COMBINATION THERAPY
  申请人：Xenon Pharmaceuticals Inc.

  公开号：EP1846035B1

  公开（公告）日：2011-09-21