4-chloro-3-cyclopropyl-1H-pyrazole-5-carboxylic acid | 1291275-83-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-chloro-3-cyclopropyl-1H-pyrazole-5-carboxylic acid
• 英文别名: 4-chloro-5-cyclopropyl-2H-pyrazole-3-carboxylic acid；4-chloro-5-cyclopropyl-1H-pyrazole-3-carboxylic acid
• CAS: 1291275-83-6
• 化学式: C₇H₇ClN₂O₂
• 分子量: 186.598
• InChiKey: NEZDRXPJTCMNCA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  66
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl 3-(4-amino-2-fluorophenoxy)azetidine-1-carboxylate 、 4-chloro-3-cyclopropyl-1H-pyrazole-5-carboxylic acid 在 N-甲基吗啉 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以69%的产率得到tert-butyl 3-[4-[(4-chloro-3-cyclopropyl-1H-pyrazole-5-carbonyl)amino]-2-fluoro-phenoxy]azetidine-1-carboxylate
  参考文献：
  名称：

  [EN] SUBSTITUTED AZETIDINE DERIVATIVES AS TAAR LIGANDS
  [FR] DÉRIVÉS D'AZÉTIDINE SUBSTITUÉS EN TANT QUE LIGANDS DE TAAR

  摘要：

  本发明涉及一种具有以下式I的化合物，其中R1是氢、甲氧基或氟；R2/R2'分别独立地是氢、甲氧基或氟；R3/R4分别独立地是氢或卤素；R是氢或氟；L1是-CH2-、-NR'-、-O-、-S-、CF2-或CH=；R'是氢或较低的烷基；L2是键、-C(0)NH-、-NH-、-CH2NHC(O)-、-NHC(O)-或-NHC(0)NH-；R是氢、卤素、较低的烷氧基、氰基或是苯环，可以选择性地被一个或多个取代基取代，所述取代基选自卤素、被卤素或较低的烷氧基取代的较低烷基、或是被卤素取代的苯环，或是一个五元或六元杂环芳基，选自吡啶基、嘧啶基、吡嗪基、吡啶嗪基或吡唑基，这些杂环芳基可以选择性地被一个或多个取代基取代，所述取代基选自卤素、较低的烷基、较低的烷氧基、氰基、环烷基、被卤素取代的较低烷基、被卤素取代的较低烷氧基或被卤素取代的苯基；N是1或2位置的环氮原子；或其药学上适宜的酸盐。式I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，可用于治疗抑郁症、焦虑症、双相情感障碍、注意缺陷多动障碍(ADHD)、与压力有关的障碍、如精神分裂症、帕金森病等神经疾病、阿尔茨海默病等神经退行性疾病、癫痫、偏头痛、高血压、物质滥用和代谢障碍，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的治疗。

  公开号：

  WO2016030310A1
• 作为产物：
  描述：

  4-chloro-5-cyclopropyl-2H-pyrazole-3-carboxylic acid ethyl ester 在 水 、 sodium hydroxide 、 盐酸 作用下， 以 1,4-二氧六环 、 水 、 乙酸乙酯 为溶剂， 反应 18.0h， 生成 4-chloro-3-cyclopropyl-1H-pyrazole-5-carboxylic acid
  参考文献：
  名称：

  [EN] 2-AMINO-5, 5-DIFLUORO-5, 6-DIHYDRO-4H-OXAZINES AS BACE 1 AND/OR BACE 2 INHIBITORS
  [FR] 2-AMINO-5,5-DIFLUORO-5,6-DIHYDRO-4H-OXAZINES EN TANT QU'INHIBITEURS DE BACE 1 ET/OU BACE 2

  摘要：

  本发明涉及具有BACE1和/或BACE2抑制活性的2-氨基-5,5-二氟-5,6-二氢-4H-[1,3]噁唑-4-基)-苯基]-酰胺衍生物的化学式(I)，其制备方法，含有它们的药物组合物以及它们作为治疗活性物质的用途。本发明的活性化合物在治疗和/或预防治疗阿尔茨海默病和2型糖尿病等疾病中具有用途。

  公开号：

  WO2011069934A1

文献信息

• [EN] MORPHOLIN-PYRIDINE DERIVATIVES<br/>[FR] DÉRIVÉS MORPHOLINE-PYRIDINE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2015165835A1

  公开（公告）日：2015-11-05

  The present invention relates to compounds of formula (I) wherein X is CR or N; R is hydrogen, halogen or lower alkyl; L is a bond, -C(O)- or -C(O)NH-; Ar is phenyl or a five or six membered heteroaryl group, containing one or two N atoms; R1 is halogen, lower alkyl, lower alkyl substituted by halogen, lower alkoxy, lower alkoxy substituted by halogen or cycloalkyl; n is 0, 1, 2 or 3; or to a pharmaceutically suitable acid addition salt thereof, to all racemic mixtures, all their corresponding enantiomers and/or optical isomers, which may be used for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders, schizophrenia, neurological diseases, Parkinson's disease, neurodegenerative disorders, Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse, metabolic disorders, 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.

  本发明涉及以下式（I）的化合物，其中X为CR或N；R为氢、卤素或较低的烷基；L为键，-C（O）-或-C（O）NH-；Ar为苯基或含有一个或两个N原子的五元或六元杂环芳基；R1为卤素、较低的烷基、被卤素取代的较低烷基、较低的烷氧基、被卤素取代的较低烷氧基或环烷基；n为0、1、2或3；或其药学适宜的酸加合物，所有外消旋混合物，所有对应的对映体和/或光学异构体，可用于治疗抑郁症、焦虑症、双相情感障碍、注意缺陷多动障碍（ADHD）、与压力有关的障碍、精神障碍、精神分裂症、神经疾病、帕金森病、神经退行性疾病、阿尔茨海默病、癫痫、偏头痛、高血压、物质滥用、代谢障碍、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、睡眠和昼夜节律障碍，以及心血管疾病。
• [EN] 2-OXA-5-AZABICYCLO[2.2.1]HEPTAN-3-YL DERIVATIVES<br/>[FR] DÉRIVÉS DU 2-OXA -5-AZABICYCLO [2.2.1] HEPTAN -3-YL
  申请人：HOFFMANN LA ROCHE

  公开号：WO2016016292A1

  公开（公告）日：2016-02-04

  The present invention relates to compounds of formula (I), wherein L is a bond, -C(O)NH-, -NHC(O)-, -CH2NHC(O)-, CH2C(O)NH-, -CH2NH-, -NH- or -NHC(O)NH-; R1 is hydrogen, lower alkyl, halogen, lower alkoxy-alkyl, lower alkoxy substituted by halogen, lower alkyl substituted by halogen or is phenyl or heteroaryl selected from the group consisting of pyridinyl, pyrimidinyl, pyrazinyl or pyrazolyl, and wherein phenyl and heteroaryl are optionally substituted by one, two or three substituents selected from the group consisting of halogen, lower alkyl, lower alkoxy, lower alkyl substituted by halogen, lower alkoxy substituted by halogen, cycloalkyl or O-CH2-cycloalkyl; or to a pharmaceutically suitable acid addition salt thereof, to all racemic mixtures, all their corresponding enantiomers and/or optical isomers, which may be used for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders, schizophrenia, neurological diseases, Parkinson's disease, neurodegenerative disorders, Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse, metabolic disorders, 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.

  本发明涉及以下化合物的公式（I），其中L是键，-C（O）NH-，-NHC（O）-，- NHC（O）-， C（O）NH-，- NH-，-NH-或-NHC（O）NH-；R1是氢，较低的烷基，卤素，较低的烷氧基烷基，受卤素取代的较低的烷氧基，受卤素取代的较低的烷基或为苯基或杂环芳基，所述苯基和杂环芳基从吡啶基、嘧啶基、吡啉基或吡唑基中选择，其中苯基和杂环芳基可以选择地被来自卤素、较低的烷基、较低的烷氧基、受卤素取代的较低的烷基、受卤素取代的较低的烷氧基、环烷基或O-CH2-环烷基的一个、两个或三个取代基取代；或其药用合适的酸盐，所有的消旋混合物，它们所有对应的对映体和/或光学异构体，可用于治疗抑郁症、焦虑症、躁郁症、注意力缺陷多动障碍（ADHD）、与压力有关的障碍、精神病性障碍、精神分裂症、神经疾病、帕金森病、神经退行性疾病、阿尔茨海默病、癫痫、偏头痛、高血压、物质滥用、代谢障碍、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、心血管障碍。
• 2-AMINO-5,5-DIFLUORO-5,6-DIHYDRO-4H-[1,3]OXAZIN-4-YL)-PHENYL]-AMIDES
  申请人：Banner David

  公开号：US20110144097A1

  公开（公告）日：2011-06-16

  The present invention relates to 2-Amino-5,5-difluoro-5,6-dihydro-4H-[1,3]oxazin-4-yl)-phenyl]-amides of formula I having BACE1 and/or BACE2 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease and type 2 diabetes.

  本发明涉及具有BACE1和/或BACE2抑制活性的2-氨基-5,5-二氟-5,6-二氢-4H-[1,3]噁唑-4-基)-苯基]-酰胺的化合物，其制备方法，含有它们的药物组合物以及它们作为治疗活性物质的用途。本发明的活性化合物可用于治疗和/或预防例如阿尔茨海默病和2型糖尿病。
• [EN] 5-OXA-2-AZABICYCLO[2.2.2]OCTAN-4-YL AND 5-OXA-2-AZABICYCLO[2.2.1]HEPTAN-4-YL DERIVATIVES AS TAAR1 MODULATORS<br/>[FR] DÉRIVÉS 5-OXA-2-AZABICYCLO[2.2.2]OCTAN-4-YL ET 5-OXA-2-AZABICYCLO[2.2.1]HEPTAN-4-YL EN TANT QUE MODULATEURS DE TAAR1
  申请人：HOFFMANN LA ROCHE

  公开号：WO2015181061A1

  公开（公告）日：2015-12-03

  The invention relates to compounds of formula (I) wherein.....C.....is -CH2- or -CH2-CH2-; X is -NH-, -C(0)NH- or -NHC(0)NH-; Ar is phenyl or a 5 or 6-membered heteroaryl group containing one or two N atoms; R1 is halogen, lower alkyl, lower alkyl substituted by halogen, lower alkoxy, lower alkoxy substituted by cycloalkyl, lower alkoxy substituted by halogen or is cycloalkyl; -( )- is -CH2-; n is 0 or 1; m is 0, 1 or 2; or to a pharmaceutically suitable acid addition salt thereof, to all racemic mixtures, all their corresponding enantiomers and/or optical isomers, which compounds may be used for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders, schizophrenia, neurological diseases, Parkinson's disease, neurodegenerative disorders, Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse, metabolic disorders, 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.

  本发明涉及式（I）的化合物，其中.....C.....是-CH2-或- - -；X是-NH-，-C(0)NH-或-NHC(0)NH-；Ar是苯基或含有一个或两个N原子的5或6元杂环芳基基团；R1是卤素、低烷基、被卤素取代的低烷基、低烷氧基、被环烷基取代的低烷氧基、被卤素取代的低烷氧基或是环烷基；-( )-是- -；n为0或1；m为0，1或2；或其药学上适宜的酸盐，所有的外消旋混合物，所有对应的对映体和/或光学异构体，这些化合物可用于治疗抑郁症、焦虑障碍、双相情感障碍、注意力缺陷多动障碍（ADHD）、与压力相关的障碍、精神障碍、精神分裂症、神经系统疾病、帕金森病、神经退行性疾病、阿尔茨海默病、癫痫、偏头痛、高血压、物质滥用、代谢障碍、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。
• 2-amino-5,5-difluoro-5,6-dihydro-4H-[1,3]oxazin-4-yl)-phenyl]-amides
  申请人：Banner David

  公开号：US08389513B2

  公开（公告）日：2013-03-05

  The present invention relates to 2-Amino-5,5-difluoro-5,6-dihydro-4H-[1,3]oxazin-4-yl)-phenyl]-amides of formula I having BACE1 and/or BACE2 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease and type 2 diabetes.

  本发明涉及具有BACE1和/或BACE2抑制活性的2-氨基-5,5-二氟-5,6-二氢-4H-[1,3]噁唑-4-基]-苯基]-酰胺的化合物，其制造、含有它们的制药组合物以及它们作为治疗活性物质的用途。本发明的活性化合物在治疗和/或预防阿尔茨海默病和2型糖尿病等方面具有用途。