(S)-1-(4-(difluoromethoxy)phenyl)-N-(4-(morpholin-2-yl)phenyl)-1H-pyrazole-3-carboxamide hydrochloride

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (S)-1-(4-(difluoromethoxy)phenyl)-N-(4-(morpholin-2-yl)phenyl)-1H-pyrazole-3-carboxamide hydrochloride
• 英文别名: 1-[4-(difluoromethoxy)phenyl]-N-[4-[(2S)-morpholin-2-yl]phenyl]pyrazole-3-carboxamide;hydrochloride
• 化学式: C₂₁H₂₀F₂N₄O₃*(x)ClH
• 分子量: 450.9
• InChiKey: BFGNCQACGVIAEF-FSRHSHDFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.81
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  77.4
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-二氟甲氧基苯胺 在 N-甲基吗啉 、 盐酸 、 tetrafluoroboric acid 、 lithium hydroxide monohydrate 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 三乙胺 、 sodium nitrite 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 20.0h， 生成 (S)-1-(4-(difluoromethoxy)phenyl)-N-(4-(morpholin-2-yl)phenyl)-1H-pyrazole-3-carboxamide hydrochloride
  参考文献：
  名称：

  [EN] PYRAZOLE DERIVATIVES
  [FR] DÉRIVÉS DE PYRAZOLE

  摘要：

  该发明涉及以下式中的化合物，其中R1是氢或苯基，可选择由卤素、CN或较低的烷氧基或由卤素取代的较低的烷氧基取代；R2是氢或较低的烷基；R3是氢或较低的烷基或是苯基，可选择由卤素、氰基或由卤素取代的较低的烷氧基取代，或是吡啶基，可选择由卤素或由卤素取代的较低的烷基取代，或是嘧啶基，可选择由较低的烷基取代的较低的烷基取代，或是吡嗪基，可选择由卤素、氰基或由卤素取代的较低的烷基取代；R4是氢、较低的烷基或苯基；Z是键，-CH2-或-O-；或其药学上适宜的酸盐。现已发现，IA和IB式的化合物对痕量胺相关受体（TAARs）具有良好的亲和力，特别是对TAAR1。这些化合物可用于治疗抑郁症、焦虑症、躁郁症、注意力缺陷多动障碍（ADHD）、与压力有关的疾病、如精神分裂症等精神疾病、帕金森病等神经系统疾病、阿尔茨海默病等神经退行性疾病、癫痫、偏头痛、高血压、物质滥用和代谢性疾病，如进食障碍、糖尿病、糖尿病并发症、肥胖症、血脂异常、能量消耗和吸收障碍、体温稳态障碍、睡眠和昼夜节律障碍以及心血管疾病。

  公开号：

  WO2012168260A1

文献信息

• PYRAZOLE DERIVATIVES
  申请人：Galley Guido

  公开号：US20120316172A1

  公开（公告）日：2012-12-13

  The invention relates to compounds of formula IA and IB wherein R 1 , R 2 , R 3 , R 4 and Z are as defined herein or to a pharmaceutically suitable acid addition salt thereof. Compounds of formulas IA and IB have a good affinity to the trace amine associated receptors (TAARs), especially for TAAR1. The compounds can be used for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders such as schizophrenia, neurological diseases such as Parkinson's disease, neurodegenerative disorders such as Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse and metabolic disorders such as eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders.

  该发明涉及式IA和IB的化合物，其中R1、R2、R3、R4和Z如本文所定义，或其药学上适宜的酸盐。式IA和IB的化合物对痕量胺相关受体（TAARs）具有良好的亲和力，特别是对TAAR1。这些化合物可用于治疗抑郁症、焦虑障碍、躁郁症、注意力缺陷多动障碍（ADHD）、与压力有关的障碍、精神分裂症等精神障碍、帕金森病等神经系统疾病、阿尔茨海默病等神经退行性疾病、癫痫、偏头痛、高血压、物质滥用和代谢性障碍，如进食障碍、糖尿病、糖尿病并发症、肥胖、血脂异常、能量消耗和吸收障碍、体温稳态障碍、睡眠和昼夜节律障碍，以及心血管疾病。
• Pyrazole derivatives
  申请人：Galley Guido

  公开号：US09073911B2

  公开（公告）日：2015-07-07

  The invention relates to compounds of formula IA and IB wherein R1, R2, R3, R4 and Z are as defined herein or to a pharmaceutically suitable acid addition salt thereof. Compounds of formulas IA and IB have a good affinity to the trace amine associated receptors (TAARs), especially for TAAR1. The compounds can be used for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders such as schizophrenia, neurological diseases such as Parkinson's disease, neurodegenerative disorders such as Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse and metabolic disorders such as eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders.

  本发明涉及公式IA和IB化合物，其中R1、R2、R3、R4和Z如本文所定义，或其药学适宜的酸加盐。公式IA和IB化合物对痕量胺相关受体（TAARs）具有良好的亲和力，特别是对TAAR1。这些化合物可用于治疗抑郁症、焦虑症、双相情感障碍、注意力缺陷多动障碍（ADHD）、与压力相关的疾病、精神疾病如精神分裂症、神经系统疾病如帕金森病、神经退行性疾病如阿尔茨海默病、癫痫、偏头痛、高血压、物质滥用和代谢性疾病如进食障碍、糖尿病、糖尿病并发症、肥胖症、血脂异常、能量消耗和吸收障碍、体温稳态障碍和功能障碍、睡眠和生物钟节律障碍以及心血管疾病等。
• US9073911B2
  申请人：——

  公开号：US9073911B2

  公开（公告）日：2015-07-07
• [EN] PYRAZOLE DERIVATIVES<br/>[FR] DÉRIVÉS DE PYRAZOLE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2012168260A1

  公开（公告）日：2012-12-13

  The invention relates to compounds of formula wherein R1 is hydrogen or phenyl, optionally substitutes by halogen, CN or lower alkoxy or lower alkoxy substituted by halogen; R2 is hydrogen or lower alkyl; R3 is hydrogen or lower alkyl or is phenyl optionally substituted by one or more substituents, selected from halogen, cyano or lower alkoxy substituted by halogen, or is pyridinyl, optionally substituted by halogen or lower alkyl substituted by halogen, or is pyrimidinyl, optionally substituted by lower alkyl substituted by halogen, or is pyrazinyl, optionally substituted by halogen, cyano or lower alkyl substituted by halogen; R4 is hydrogen, lower alkyl or phenyl; Z is a bond, -CH2- or -O-; or to a pharmaceutically suitable acid addition salt thereof. It has now been found that the compounds of formulas IA and IB have a good affinity to the trace amine associated receptors (TAARs), especially for TAAR1. The compounds may be used for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders such as schizophrenia, neurological diseases such as Parkinson's disease, neurodegenerative disorders such as Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse and metabolic disorders such as eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders.

  该发明涉及以下式中的化合物，其中R1是氢或苯基，可选择由卤素、CN或较低的烷氧基或由卤素取代的较低的烷氧基取代；R2是氢或较低的烷基；R3是氢或较低的烷基或是苯基，可选择由卤素、氰基或由卤素取代的较低的烷氧基取代，或是吡啶基，可选择由卤素或由卤素取代的较低的烷基取代，或是嘧啶基，可选择由较低的烷基取代的较低的烷基取代，或是吡嗪基，可选择由卤素、氰基或由卤素取代的较低的烷基取代；R4是氢、较低的烷基或苯基；Z是键，-CH2-或-O-；或其药学上适宜的酸盐。现已发现，IA和IB式的化合物对痕量胺相关受体（TAARs）具有良好的亲和力，特别是对TAAR1。这些化合物可用于治疗抑郁症、焦虑症、躁郁症、注意力缺陷多动障碍（ADHD）、与压力有关的疾病、如精神分裂症等精神疾病、帕金森病等神经系统疾病、阿尔茨海默病等神经退行性疾病、癫痫、偏头痛、高血压、物质滥用和代谢性疾病，如进食障碍、糖尿病、糖尿病并发症、肥胖症、血脂异常、能量消耗和吸收障碍、体温稳态障碍、睡眠和昼夜节律障碍以及心血管疾病。