methyl 6-(4-(2-(trifluoromethyl)benzoyl)piperazin-1-yl)-pyridazine-3-carboxylate | 840488-99-5

• 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: methyl 6-(4-(2-(trifluoromethyl)benzoyl)piperazin-1-yl)-pyridazine-3-carboxylate
• 英文别名: 6-[4-(2-trifluoromethylbenzoyl)piperazin-1-yl]pyridazine-3-carboxylic acid methyl ester；methyl 6-[4-[2-(trifluoromethyl)benzoyl]piperazin-1-yl]pyridazine-3-carboxylate
• CAS: 840488-99-5
• 化学式: C₁₈H₁₇F₃N₄O₃
• 分子量: 394.353
• InChiKey: GEYJRAIMMCYSLF-UHFFFAOYSA-N

物化性质

• 沸点：
  599.3±50.0 °C(Predicted)
• 密度：
  1.371±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  75.6
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  methyl 6-(4-(2-(trifluoromethyl)benzoyl)piperazin-1-yl)-pyridazine-3-carboxylate 在 氯化亚砜 、 lithium hydroxide monohydrate 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 氯仿 、 水 为溶剂， 反应 28.0h， 生成 6-[4-(2-trifluoromethylbenzoyl)piperazin-1-yl]pyridazine-3-carboxylic acid phenylamide
  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 盐酸 、 四丁基碘化铵 、 potassium carbonate 、 三乙胺 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 乙醚 、 二氯甲烷 为溶剂， 反应 47.0h， 生成 methyl 6-(4-(2-(trifluoromethyl)benzoyl)piperazin-1-yl)-pyridazine-3-carboxylate
  参考文献：
  名称：

  Piperazine derivatives and their use as therapeutic agents

  摘要：

  公开号：

  EP2316827B1

文献信息

• Pyridazine derivatives and their use as therapeutic agents
  申请人：Chakka Nagasree

  公开号：US20060009459A1

  公开（公告）日：2006-01-12

  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 (Ia): 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. Pharmaceutical compositions comprising the compounds of formula (I) are also disclosed.

  本发明涉及一种治疗哺乳动物（优选为人类）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(Ia)的化合物，其中x、y、W、V、R2、R3、R4、R5、R6、R6a、R7、R7a、R8、R8a、R9和R9a如本文所定义。此外，本发明还涉及含有式(I)的化合物的制药组合物。
• Heterocyclic Derivatives and Their Use as Stearoyl-Coa Desaturase Inhibitors
  申请人：Kamboj Rajender

  公开号：US20080096895A1

  公开（公告）日：2008-04-24

  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 x, y, G, J, K, L, M, V R 2 , R 3 , R 4 , R 5 , R 5a , R 6 , R 6a , R 7 , R 7a , R 8 and R 8a are defined herein. Pharmaceutical compositions comprising the compounds of formula (I) are also disclosed.

  本文披露了一种治疗哺乳动物（最好是人类）SCD介导的疾病或病症的方法，其中方法包括向需要该方法的哺乳动物施用式（I）的化合物：其中x、y、G、J、K、L、M、V、R2、R3、R4、R5、R5a、R6、R6a、R7、R7a、R8和R8a在本文中有定义。本文还披露了包含式（I）化合物的药物组合物。
• 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。
• Heteroaromatic Compounds As Inhibitors Of Stearoyl-Coenzyme A Delta-9 Desaturase
  申请人：Black Cameron

  公开号：US20090118296A1

  公开（公告）日：2009-05-07

  Heteroaromatic compounds of structural formula (I) are selective inhibitors of stearoyl-coenzyme A delta-9 desaturase (SCD1) relative to other known stearoyl-coenzyme A desaturases. The compounds of the present invention are useful for the prevention and treatment of conditions related to abnormal lipid synthesis and metabolism, including cardiovascular disease; atherosclerosis; lipid disorders; obesity; diabetes; neurological disease; metabolic syndrome; insulin resistance; and fatty liver disease.

  结构式（I）的杂环芳香化合物是选择性的硬脂酰辅酶A-Δ9-脱饱和酶（SCD1）抑制剂，相对于其他已知的硬脂酰辅酶A脱饱和酶。本发明的化合物对于预防和治疗与异常脂质合成和代谢有关的疾病非常有用，包括心血管疾病、动脉粥样硬化、脂质代谢紊乱、肥胖症、糖尿病、神经系统疾病、代谢综合征、胰岛素抵抗和脂肪肝病。
• Heterocyclic derivatives and their use as stearoyl-CoA desaturase inhibitors
  申请人：Xenon Pharmaceuticals Inc.

  公开号：US07767677B2

  公开（公告）日：2010-08-03

  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 x, y, G, J, K, L, M, V R2, R3, R4, R5, R5a, R6, R6a, R7, R7a, R8 and R8a 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，尤其是人类SCD介导的疾病或病况的方法，其中该方法包括向需要该药物的哺乳动物内给予化合物(I)的方法，其中化合物(I)的公式如下：其中x、y、G、J、K、L、M、V、R2、R3、R4、R5、R5a、R6、R6a、R7、R7a、R8和R8a在此定义。本发明还揭示了包含化合物(I)的制药组合物。