6-[4-(2-trifluoromethylbenzoyl)piperazin-1-yl]pyridazine-3-carboxylic acid (1H-benzoimidazol-2-yl)amide | 840493-12-1

• 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 (1H-benzoimidazol-2-yl)amide
• 英文别名: N-(1H-benzimidazol-2-yl)-6-[4-[2-(trifluoromethyl)benzoyl]piperazin-1-yl]pyridazine-3-carboxamide
• CAS: 840493-12-1
• 化学式: C₂₄H₂₀F₃N₇O₂
• 分子量: 495.464
• InChiKey: SLQTUMVIMBTKIA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  36
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  107
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 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 (1H-benzoimidazol-2-yl)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 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
• JP4808616B2
  申请人：——

  公开号：JP4808616B2

  公开（公告）日：2011-11-02