N-(2-cyclopropylethyl)-6-(piperazin-1-yl)pyridazine-3-carboxamide | 840488-88-2

• 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-(2-cyclopropylethyl)-6-(piperazin-1-yl)pyridazine-3-carboxamide
• 英文别名: 6-piperazin-1-yl-pyridazine-3-carboxylic acid (2-cyclopropylethyl)amide；N-(2-cyclopropylethyl)-6-(1-piperazinyl)-3-pyridazinecarboxamide；N-(2-cyclopropylethyl)-6-piperazin-1-ylpyridazine-3-carboxamide
• CAS: 840488-88-2
• 化学式: C₁₄H₂₁N₅O
• 分子量: 275.354
• InChiKey: DCRBBFSMVSLOKM-UHFFFAOYSA-N

物化性质

• 沸点：
  579.9±45.0 °C(Predicted)
• 密度：
  1.195±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  70.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(2-cyclopropylethyl)-6-(piperazin-1-yl)pyridazine-3-carboxamide 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 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 18.25h， 生成 2-{4-[6-(2-cyclopropylethylcarbamoyl)pyridazin-3-yl]piperazine-1-carbonyl}benzoic acid
  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：

  环丙乙腈 在 lithium aluminium tetrahydride 、 硫酸 、 1-羟基苯并三唑 、 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 作用下， 以 乙醚 、 二氯甲烷 、 乙腈 为溶剂， 反应 40.25h， 生成 N-(2-cyclopropylethyl)-6-(piperazin-1-yl)pyridazine-3-carboxamide
  参考文献：
  名称：

  Piperazine derivatives and their use as therapeutic agents

  摘要：

  公开号：

  EP2316827B1

文献信息

• Heterocyclic Derivatives and Their Use as Strearoyl-Coa Desaturase Inhibitors
  申请人：Kamboj Rajender

  公开号：US20080125434A1

  公开（公告）日：2008-05-29

  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 x, y, G, J, K, L, M, W, R 2 , R 3 , 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.

  本发明揭示了一种治疗哺乳动物（优选为人类）SCD介导的疾病或病症的方法，其中该方法包括向需要治疗的哺乳动物施用化合物I的方法：其中x、y、G、J、K、L、M、W、R2、R3、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的药物组合物。
• 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：US20090306090A1

  公开（公告）日：2009-12-10

  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, W, R 2 , R 3 , 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.

  本发明涉及用于治疗哺乳动物，尤其是人体中SCD介导的疾病或病况的方法，其中所述方法包括向需要治疗的哺乳动物中给予化合物(I)的组合物，其中x、y、G、J、K、L、M、W、R2、R3、R5、R5a、R6、R6a、R7、R7a、R8和R8a在此定义。还公开了含有化合物(I)的制药组合物。
• 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。
• Pyridazine-piperazine compounds and their use as stearoyl-CoA desaturase inhibitors
  申请人：Xenon Pharmaceuticals Inc.

  公开号：US07592343B2

  公开（公告）日：2009-09-22

  Compounds of formula (Ia): where x, y, G, L, M, W, R2, R3, R5, R5a, R6, R6a, R7, R7a, R8 and R8a are defined herein, are disclosed, as well as pharmaceutical compositions comprising the compounds. These compounds and pharmaceutical compositions are useful in treating SCD-mediated diseases or conditions.

  公式（Ia）的复合物：其中x，y，G，L，M，W，R2，R3，R5，R5a，R6，R6a，R7，R7a，R8和R8a的定义如本文所述，以及包含这些化合物的制药组合物已经披露。这些化合物和制药组合物在治疗SCD介导的疾病或病况方面是有用的。