ethyl 1-(4-(trifluoromethoxy)phenyl)-1H-pyrazole-4-carboxylate | 1202942-22-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 1-(4-(trifluoromethoxy)phenyl)-1H-pyrazole-4-carboxylate
• 英文别名: ethyl 1-[4-(trifluoromethoxy)phenyl]-1H-pyrazole-4-carboxylate；ethyl 1-[4-(trifluoromethoxy)phenyl]pyrazole-4-carboxylate
• CAS: 1202942-22-0
• 化学式: C₁₃H₁₁F₃N₂O₃
• 分子量: 300.237
• InChiKey: YYIXIHDJQDVVCB-UHFFFAOYSA-N

物化性质

• 沸点：
  333.8±42.0 °C(Predicted)
• 密度：
  1.34±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  53.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl 1-(4-(trifluoromethoxy)phenyl)-1H-pyrazole-4-carboxylate 在 lithium aluminium tetrahydride 、 三溴化磷 作用下， 以 乙醚 为溶剂， 反应 2.0h， 生成 4-(bromomethyl)-1-[4-(trifluoromethoxy)phenyl]-1H-pyrazole
  参考文献：
  名称：

  [EN] NITROIMIDAZOOXAZINES AND THEIR USES IN ANTI-TUBERCULAR THERAPY
  [FR] NITROIMIDAZOOXAZINES ET LEURS UTILISATIONS EN THÉRAPIE ANTITUBERCULEUSE

  摘要：

  本发明涉及新型硝基咪唑噁啉类化合物，其制备方法，以及它们作为治疗结核分枝杆菌和其他微生物感染的药物的用途，可以单独使用或与其他抗感染治疗方法结合使用。

  公开号：

  WO2011014774A1
• 作为产物：
  描述：

  (E)-2-氰基-3-乙氧基丙烯酸乙酯 在 sodium acetate 、 溶剂黄146 、 亚硝酸异戊酯 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 35.0h， 生成 ethyl 1-(4-(trifluoromethoxy)phenyl)-1H-pyrazole-4-carboxylate
  参考文献：
  名称：

  NITROIMIDAZOOXAZINES AND THEIR USES IN ANTI-TUBERCULAR THERAPY

  摘要：

  本发明涉及新型硝基咪唑噁啉类化合物，其制备方法，以及它们作为治疗结核分枝杆菌和其他微生物感染的药物的用途，可以单独使用或与其他抗感染治疗联合使用。

  公开号：

  US20120028973A1

文献信息

• [EN] NITROIMIDAZOOXAZINES AND THEIR USES IN ANTI-TUBERCULAR THERAPY<br/>[FR] NITROIMIDAZOOXAZINES ET LEURS UTILISATIONS EN THÉRAPIE ANTITUBERCULEUSE
  申请人：GLOBAL ALLIANCE FOR TB DRUG DEV

  公开号：WO2011014774A1

  公开（公告）日：2011-02-03

  The present invention relates to novel nitroimidazooxazines, to their preparation, and to their use as drugs for treating Mycobacterium tuberculosis and other microbial infections, either alone or in combination with other anti-infective treatments.

  本发明涉及新型硝基咪唑噁啉类化合物，其制备方法，以及它们作为治疗结核分枝杆菌和其他微生物感染的药物的用途，可以单独使用或与其他抗感染治疗方法结合使用。
• [EN] PYRAZOLE CARBOXAMIDE DERIVATIVES AS TAAR MODULATORS FOR USE IN THE TREATMENT OF SEVERAL DISORDERS, SUCH AS DEPRESSION, DIABETES AND PARKINSON'S DISEASE<br/>[FR] DÉRIVÉS DE PYRAZOLE-CARBOXAMIDE EN TANT QUE MODULATEURS DE TAAR POUR UTILISATION DANS LE TRAITEMENT DE PLUSIEURS TROUBLES, TELS QUE LA DÉPRESSION, LE DIABÈTE ET LA MALADIE DE PARKINSON
  申请人：HOFFMANN LA ROCHE

  公开号：WO2014041007A1

  公开（公告）日：2014-03-20

  The present invention relates to compounds of formula (I) wherein R1 is phenyl, optionally substituted by halogen, lower alkyl, lower cycloalkyl, lower alkoxy, cyano, lower alkyl substituted by halogen, lower alkyl substituted by hydroxy, lower alkoxy substituted by halogen or lower alkoxy substituted by hydroxy; or is pyridine-2, 3 or 4-yl, optionally substituted by halogen, lower alkyl, lower cycloalkyl, cyano, lower alkyl substituted by halogen, lower alkyl substituted by hydroxy, lower alkoxy, lower alkoxy substituted by halogen or lower alkoxy substituted by hydroxyl; or is pyrimidin-2, 4 or 5-yl, optionally substituted by halogen, lower alkyl, lower cycloalkyl, lower alkyl substituted by hydroxy or lower alkyl substituted by halogen; or is pyrazin-2-yl, optionally substituted by halogen, lower alkyl, lower cycloalkyl, lower alkyl substituted by halogen, lower alkyl substituted by hydroxy or cyano; or is 2,2-difluorobenzo[d][l,3]dioxol-5-yl, or is thiazolyl, optionally substituted by lower alkyl substituted by halogen; R2 is hydrogen or lower alkyl; R3 is hydrogen, amino or lower alkyl; 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 I 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.

  本发明涉及以下式（I）的化合物，其中R1是苯基，可以被卤素、较低烷基、较低环烷基、较低烷氧基、氰基、被卤素取代的较低烷基、被羟基取代的较低烷基、被卤素取代的较低烷氧基或被羟基取代的较低烷氧基；或是吡啶-2、3或4-基，可以被卤素、较低烷基、较低环烷基、氰基、被卤素取代的较低烷基、被羟基取代的较低烷基、较低烷氧基、被卤素取代的较低烷氧基或被羟基取代的较低烷氧基取代；或是嘧啶-2、4或5-基，可以被卤素、较低烷基、较低环烷基、被羟基取代的较低烷基或被卤素取代的较低烷基取代；或是吡嗪-2-基，可以被卤素、较低烷基、较低环烷基、被卤素取代的较低烷基、被羟基取代的较低烷基或氰基取代；或是2,2-二氟苯并[d][1,3]二氧杂环-5-基，或是噻唑基，可以被被卤素取代的较低烷基取代；R2是氢或较低烷基；R3是氢、氨基或较低烷基；Z是键，-CH2-或-O-；或其药学上适用的酸盐。现已发现，式I的化合物对追踪胺相关受体（TAARs）有很好的亲和力，尤其是对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、物质滥用以及代谢障碍，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。
• GLYCINE TRANSPORTER INHIBITING SUBSTANCES
  申请人：Moriya Minoru

  公开号：US20130184460A1

  公开（公告）日：2013-07-18

  The present invention aims to provide novel compounds of formula [I] or pharmaceutically acceptable salts thereof that are based on a glycine uptake inhibiting action and which are useful in the prevention or treatment of such diseases as schizophrenia, Alzheimer's disease, cognitive dysfunction, dementia, anxiety disorders (generalized anxiety disorder, panic disorder, obsessive-compulsive disorder, social anxiety disorder, posttraumatic stress disorder, specific phobia, acute stress disorder, etc.), depression, drug addiction, spasm, tremor, pain, and sleep disorder:

  本发明旨在提供基于甘氨酸摄取抑制作用的化合物的新颖化合物，其化学式为[I]或其药学上可接受的盐，可用于预防或治疗精神分裂症、阿尔茨海默病、认知功能障碍、痴呆、焦虑障碍（广泛性焦虑障碍、恐慌障碍、强迫症、社交焦虑障碍、创伤后应激障碍、特定恐惧症、急性应激障碍等）、抑郁症、药物成瘾、痉挛、震颤、疼痛和睡眠障碍等疾病的预防或治疗。
• Glycine transporter inhibiting substances
  申请人：Moriya Minoru

  公开号：US08729271B2

  公开（公告）日：2014-05-20

  The present invention aims to provide novel compounds of formula [I] or pharmaceutically acceptable salts thereof that are based on a glycine uptake inhibiting action and which are useful in the prevention or treatment of such diseases as schizophrenia, Alzheimer's disease, cognitive dysfunction, dementia, anxiety disorders (generalized anxiety disorder, panic disorder, obsessive-compulsive disorder, social anxiety disorder, posttraumatic stress disorder, specific phobia, acute stress disorder, etc.), depression, drug addiction, spasm, tremor, pain, and sleep disorder:

  本发明旨在提供公式[I]的新化合物或其药学上可接受的盐，其基于甘氨酸摄取抑制作用，并且在预防或治疗精神分裂症、阿尔茨海默病、认知功能障碍、痴呆、焦虑症（广泛性焦虑症、惊恐症、强迫症、社交焦虑症、创伤后应激障碍、特定恐惧症、急性应激障碍等）、抑郁症、药物成瘾、痉挛、震颤、疼痛和睡眠障碍方面有用。
• PYRAZOLE CARBOXAMIDE COMPOUNDS AND USES THEREOF
  申请人：Hoffmann-La Roche Inc.

  公开号：US20150218131A1

  公开（公告）日：2015-08-06

  The present invention relates to compounds of formula wherein R 1 is phenyl, optionally substituted by halogen, lower alkyl, lower cycloalkyl, lower alkoxy, cyano, lower alkyl substituted by halogen, lower alkyl substituted by hydroxy, lower alkoxy substituted by halogen or lower alkoxy substituted by hydroxy; or is pyridine-2, 3 or 4-yl, optionally substituted by halogen, lower alkyl, lower cycloalkyl, cyano, lower alkyl substituted by halogen, lower alkyl substituted by hydroxy, lower alkoxy, lower alkoxy substituted by halogen or lower alkoxy substituted by hydroxyl; or is pyrimidin-2, 4 or 5-yl, optionally substituted by halogen, lower alkyl, lower cycloalkyl, lower alkyl substituted by hydroxy or lower alkyl substituted by halogen; or is pyrazin-2-yl, optionally substituted by halogen, lower alkyl, lower cycloalkyl, lower alkyl substituted by halogen, lower alkyl substituted by hydroxy or cyano; or is 2,2-difluorobenzo[d][1,3]dioxol-5-yl, or is thiazolyl, optionally substituted by lower alkyl substituted by halogen; R 2 is hydrogen or lower alkyl; R 3 is hydrogen, amino or lower alkyl; Z is a bond, —CH 2 — or —O—; or to a pharmaceutically suitable acid addition salt thereof. It has now been found that the compounds of formulas I 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.

  本发明涉及以下式的化合物： 其中， R1是苯基，可以被卤素、低烷基、低环烷基、低烷氧基、氰基、被卤素取代的低烷基、被羟基取代的低烷基、被卤素取代的低烷氧基或被羟基取代的低烷氧基；或是吡啶-2、3或4-基，可以被卤素、低烷基、低环烷基、氰基、被卤素取代的低烷基、被羟基取代的低烷基、低烷氧基、被卤素取代的低烷氧基或被羟基取代的低烷氧基取代； 或是嘧啶-2、4或5-基，可以被卤素、低烷基、低环烷基、被羟基取代的低烷基或被卤素取代的低烷基取代； 或是吡唑-2-基，可以被卤素、低烷基、低环烷基、被卤素取代的低烷基、被羟基取代的低烷基或氰基取代； 或是2,2-二氟苯并[d][1,3]二氧杂环-5-基； 或是噻唑基，可以被被卤素取代的低烷基取代； R2是氢或低烷基； R3是氢、氨基或低烷基； Z是键，-CH2-或-O-； 或是其药学上适宜的酸盐。 现已发现，式I的化合物对微量胺基关联受体(TAARs)具有良好的亲和力，尤其是对TAAR1。 该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)、压力相关障碍、精神疾病如精神分裂症、神经疾病如帕金森病、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、睡眠和昼夜节律障碍以及心血管疾病的治疗。