2-chloro-1-(3-methyl-4-nitrophenyl)ethanone | 1400997-21-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-chloro-1-(3-methyl-4-nitrophenyl)ethanone
• 英文别名: 2-Chloro-1-(3-methyl-4-nitrophenyl)ethanone
• CAS: 1400997-21-8
• 化学式: C₉H₈ClNO₃
• 分子量: 213.62
• InChiKey: SRZQNPWJNHMSGZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  62.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-bromo-1-(3-methyl-4-nitrophenyl)ethanone 、 2-chloro-1-(3-methyl-4-nitrophenyl)ethanone 、 硼氢化钠 、 sodium methylate 在 Brine 、 Sodium sulfate-III 作用下， 以 乙醇 、 乙酸乙酯 为溶剂， 反应 18.08h， 以to afford (RS)-2-(3-methyl-4-nitrophenyl)oxirane (4.63 g, 94% over 2 steps) as a yellow oil的产率得到(RS)-2-(3-methyl-4-nitrophenyl)oxirane
  参考文献：
  名称：

  Heterocyclic amine derivatives

  摘要：

  本发明涉及公式I的化合物，其中A、B、X、Y、Ar、R1、R2、R'、m和n的定义如本文所述，并且涉及其药物活性酸盐，具有良好的亲和力与追踪胺相关受体TAAR1，因此可以用于治疗抑郁症、焦虑症和双相障碍。

  公开号：

  US08802673B2
• 作为产物：
  描述：

  3-甲基-4-硝基苯甲酰氯 、 三甲基硅烷化重氮甲烷 在 氢溴酸 作用下， 以 四氢呋喃 、 正己烷 、 乙腈 为溶剂， 反应 1.5h， 生成 2-bromo-1-(3-methyl-4-nitrophenyl)ethanone 、 2-chloro-1-(3-methyl-4-nitrophenyl)ethanone
  参考文献：
  名称：

  SUBSTITUTED BENZAMIDE DERIVATIVES

  摘要：

  本发明涉及以下式中的化合物，其中R1、R2、R3、X、Z、Ar和n如索权所述，Ar为苯基或杂环芳基，所述杂环芳基选自以下群体：1H-吲哚基、吡啶-2-基、吡啶-3-基、吡啶-4-基、嘧啶-5-基、1H-吡唑-3-基、1H-吡唑-4-基和1H-吡唑-5-基；或其药学上适用的酸加盐，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。

  公开号：

  US20120316165A1

文献信息

• SUBSTITUTED BENZAMIDE DERIVATIVES
  申请人：Galley Guido

  公开号：US20120316165A1

  公开（公告）日：2012-12-13

  The present invention relates to compounds of formula wherein R 1 , R 2 , R 3 , X, Z, Ar, and n are as described in the claims, Ar is phenyl or heteroaryl, selected from the group consisting of 1H-indazole-3yl, pyridine-2-yl, pyridine-3-yl, pyridine-4-yl, pyrimidine-5-yl, 1H-pyrazole-3-yl, 1H-pyrazole-4-yl and 1H-pyrazole-5-yl; or to a pharmaceutically suitable acid addition salt thereof, 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.

  本发明涉及以下式中的化合物，其中R1、R2、R3、X、Z、Ar和n如索权所述，Ar为苯基或杂环芳基，所述杂环芳基选自以下群体：1H-吲哚基、吡啶-2-基、吡啶-3-基、吡啶-4-基、嘧啶-5-基、1H-吡唑-3-基、1H-吡唑-4-基和1H-吡唑-5-基；或其药学上适用的酸加盐，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。
• [EN] SUBSTITUTED BENZAMIDE DERIVATIVES<br/>[FR] DÉRIVÉS DE BENZAMIDE SUBSTITUÉS
  申请人：HOFFMANN LA ROCHE

  公开号：WO2012168265A1

  公开（公告）日：2012-12-13

  The present invention relates to compounds of formula (I) wherein R1 is hydrogen, halogen, cyano, lower alkyl, lower alkyl substituted by halogen, lower alkoxy, lower alkoxy substituted by halogen or C(O)NH2, or is phenyl optionally substituted by halogen, cyano or lower alkoxy substituted by halogen, or is 2,2-difluorobenzo[d][1,3]dioxol-5-yl, or is 6-(trifluoromethyl)pyrazin-2-yl or 5-(trifluoromethyl)pyrazin-2-yl or is 6-(trifluoromethyl)pyrimidin-4-yl, or is 6- (trifluoromethyl)pyridin-3-yl, or is 5-cyanopyrazin-2-yl or is 2- (trifluoromethyl)pyrimidin-4-yl; n is 1 or 2 R2 is halogen, lower alkyl or cyano and R3 is hydrogen, or R2 is hydrogen and R3 is halogen, lower alkyl or cyano; X is a bond, -NR'-, -CH2NH- or -CHR'-; R' is hydrogen or lower alkyl; Z is a bond, -CH2- or -O-; Ar is phenyl or is heteroaryl, selected from the group consisting of 1H-indazole-3yl, pyridine-2-yl, pyridine-3-yl, pyridine-4-yl, pyrimidine-5-yl, lH-pyrazole-3-yl, 1H- pyrazole-4-yl or lH-pyrazole-5-yl; or to a pharmaceutically suitable acid addition salt thereof, 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，其化学式为（I）其中R1为氢、卤素、氰基、较低的烷基、卤素取代的较低烷基、较低的烷氧基、卤素取代的较低烷氧基或C（O）NH2，或为苯基，可选择地被卤素、氰基或卤素取代的较低烷氧基取代，或为2,2-二氟苯并[d][1,3]二噁唑-5-基，或为6-（三氟甲基）吡嗪-2-基或5-（三氟甲基）吡嗪-2-基或6-（三氟甲基）嘧啶-4-基，或为6-（三氟甲基）吡啶-3-基，或为5-氰基吡嗪-2-基或为2-（三氟甲基）嘧啶-4-基；n为1或2，R2为卤素、较低烷基或氰基，R3为氢，或R2为氢，R3为卤素、较低烷基或氰基；X为键，-NR'-，-CH2NH-或-CHR'-；R'为氢或较低烷基；Z为键，-CH2-或-O-；Ar为苯基或杂环芳基，选自由1H-吲唑-3-基、吡啶-2-基、吡啶-3-基、吡啶-4-基、嘧啶-5-基、1H-吡唑-3-基、1H-吡唑-4-基或1H-吡唑-5-基；或其药学上适宜的酸盐，可用于治疗抑郁症、焦虑症、躁郁症、注意缺陷多动障碍（ADHD）、与压力相关的疾病、精神疾病、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、代谢紊乱、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。
• [EN] HETEROCYCLIC AMINE DERIVATIVES<br/>[FR] DÉRIVÉS D'AMINES HÉTÉROCYCLIQUES
  申请人：HOFFMANN LA ROCHE

  公开号：WO2012126922A1

  公开（公告）日：2012-09-27

  The present invention relates to compounds of formula (I) wherein R1 is hydrogen, lower alkyl, halogen, lower alkyl substituted by halogen, lower alkoxy, lower alkoxy substituted by halogen, cyano, nitro, C3-6-cycloalkyl, -CH2-C3-6-cycloalkyl, -O-CH2-C3-6-cycloalkyl, -O-(CH2)2-O-lower alkyl, S(O)2CH3, SF5, -C(O)NH-lower alkyl, phenyl, -O-pyrimidinyl, optionally substituted by lower alkoxy substituted by halogen, or is benzyl, oxetanyl or furanyl; m Ar is aryl or heteroaryl, selected from the group consisting of phenyl, naphthyl, pyrimidinyl, pyridinyl, benzothiazolyl, quinolinyl, quinazolinyl, benzo[d][1.3]dioxolyl, 5,6,7,8- tetrahydro-quinazolinyl, pyrazolyl, pyrazinyl, pyridazinyl, or 1,3,4-oxadiazolyl; Y is a bond, -CH2-, -CH2CH2-, -CH(CF3)- or -CH(CH3)-; R2 is hydrogen or lower alkyl; A is CR or N; and R is hydrogen, cyano, halogen or lower alkyl; R' is hydrogen or halogen; with the proviso that when R' is halogen, then A is CH; B is CH or N; n is 0, 1 or 2; X is a bond, -CH2- or -O-; pharmaceutical active acid addition salts thereof. It has now been found that the compounds of formula 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是氢、低碳基、卤素、被卤素取代的低碳基、低烷氧基、被卤素取代的低烷氧基、氰基、硝基、C3-6环烷基、-CH2-C3-6环烷基、-O-CH2-C3-6环烷基、-O-(CH2)2-O-低碳基、S(O)2CH3、SF5、-C(O)NH-低碳基、苯基、-O-嘧啶基，或是被低烷氧基取代的被卤素取代的苯基、或者是苄基、氧杂环戊二烯基或呋喃基；m Ar是芳基或杂芳基，选自苯基、萘基、嘧啶基、吡啶基、苯并噻唑基、喹啉基、喹唑啉基、苯并[d][1.3]二噁基、5,6,7,8-四氢喹唑啉基、吡唑基、吡嗪基、吡啶啉基或1,3,4-噁二唑基；Y是键、-CH2-、-CH2CH2-、-CH(CF3)-或-CH(CH3)-；R2是氢或低碳基；A是CR或N；R是氢、氰基、卤素或低碳基；R'是氢或卤素；但是如果R'是卤素，则A是CH；B是CH或N；n是0、1或2；X是键、-CH2-或-O-；以及它们的药用活性酸盐。现已发现，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。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、物质滥用以及代谢障碍，如进食障碍、糖尿病、糖尿病并发症、肥胖症、脂质代谢异常、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。
• Heterocyclic amine derivatives
  申请人：Galley Guido

  公开号：US08802673B2

  公开（公告）日：2014-08-12

  The present invention relates to compounds of formula I wherein A, B, X, Y, Ar, R1, R2, R′, m and n are as defined herein and to pharmaceutical active acid addition salts thereof, which have a good affinity to the trace amine associated receptors TAAR1, so that they can be used for the treatment of depression, anxiety disorders and bipolar disorder.

  本发明涉及公式I的化合物，其中A、B、X、Y、Ar、R1、R2、R'、m和n的定义如本文所述，并且涉及其药物活性酸盐，具有良好的亲和力与追踪胺相关受体TAAR1，因此可以用于治疗抑郁症、焦虑症和双相障碍。
• US8802673B2
  申请人：——

  公开号：US8802673B2

  公开（公告）日：2014-08-12