(RS)-2-[4-(4-chloro-benzoylamino)-benzyl]-pyrrolidine-1-carboxylic acid tert-butyl ester | 1312565-68-6

• 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: (RS)-2-[4-(4-chloro-benzoylamino)-benzyl]-pyrrolidine-1-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl 2-[[4-[(4-chlorobenzoyl)amino]phenyl]methyl]pyrrolidine-1-carboxylate
• CAS: 1312565-68-6
• 化学式: C₂₃H₂₇ClN₂O₃
• 分子量: 414.932
• InChiKey: UZBUAQDNMHBRHN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (RS)-2-[4-(4-chloro-benzoylamino)-benzyl]-pyrrolidine-1-carboxylic acid tert-butyl ester 在 盐酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 以22%的产率得到(RS)-4-chloro-N-(4-pyrrolidin-2-ylmethyl-phenyl)-benzamide hydrochloride
  参考文献：
  名称：

  SUBSTITUTED BENZAMIDES

  摘要：

  该发明涉及以下式的化合物 其中R、R1、R2、X和Y如本文所定义，并且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。这些化合物可用于治疗抑郁症、焦虑障碍、双相情感障碍、注意缺陷多动障碍（ADHD）、与压力有关的障碍、如精神分裂症的精神障碍、如帕金森病的神经疾病、如阿尔茨海默病的神经退行性疾病、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：

  US20110152245A1
• 作为产物：
  描述：

  tert-butyl 2-(4-bromobenzyl)pyrrolidine-1-carboxylate 、 4-氯苯甲酰胺 在 copper(l) iodide 、 caesium carbonate 、 N,N'-二甲基乙二胺 作用下， 以 1,4-二氧六环 为溶剂， 反应 18.0h， 以4%的产率得到(RS)-2-[4-(4-chloro-benzoylamino)-benzyl]-pyrrolidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  SUBSTITUTED BENZAMIDES

  摘要：

  该发明涉及以下式的化合物 其中R、R1、R2、X和Y如本文所定义，并且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。这些化合物可用于治疗抑郁症、焦虑障碍、双相情感障碍、注意缺陷多动障碍（ADHD）、与压力有关的障碍、如精神分裂症的精神障碍、如帕金森病的神经疾病、如阿尔茨海默病的神经退行性疾病、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：

  US20110152245A1

文献信息

• SUBSTITUTED BENZAMIDES
  申请人：Groebke Zbinden Katrin

  公开号：US20110152245A1

  公开（公告）日：2011-06-23

  The invention relates to compounds of formula wherein R, R 1 , R 2 , X, and Y are as defined herein and to a pharmaceutically suitable acid addition salt thereof. Compounds of formula I 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.

  该发明涉及以下式的化合物 其中R、R1、R2、X和Y如本文所定义，并且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。这些化合物可用于治疗抑郁症、焦虑障碍、双相情感障碍、注意缺陷多动障碍（ADHD）、与压力有关的障碍、如精神分裂症的精神障碍、如帕金森病的神经疾病、如阿尔茨海默病的神经退行性疾病、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。
• SUBSTITUTED BENZAMIDE DERIVATIVES
  申请人：F. Hoffmann-La Roche AG

  公开号：EP3187490A1

  公开（公告）日：2017-07-05

  The invention relates to compounds of formula wherein R is hydrogen or lower alkyl; R1 is -(CH2)n-(O)o-heterocycloalkyl or -C(O)-heterocycloalkyl, wherein the heterocycloalkyl group is optionally substituted by lower alkyl, hydroxy, halogen or by -(CH2)p-aryl; n is 0, 1 or 2; o is 0 or 1; p is 0, 1 or 2; R2 is CF3, cycloalkyl, optionally substituted by lower alkoxy or halogen, or is indan-2-yl, or is heterocycloalkyl, optionally substituted by heteroaryl, or is aryl or heteroaryl, wherein the aromatic rings are optionally substituted by one or two substituents, selected from lower alkyl, halogen, heteroaryl, hydroxy, CF3, OCF3, OCH2CF3, OCH2-cycloalkyl, OCH2C(CH2OH)(CH2Cl)(CH3), S-lower alkyl, lower alkoxy, CH2-lower alkoxy, lower alkinyl or cyano, or by-C(O)-phenyl, -O-phenyl, -O-CH2-phenyl, phenyl or -CH2-phenyl, and wherein the phenyl rings may optionally be substituted by halogen, -C(O)-lower alkyl, -C(O)OH or -C(O)O-lower alkyl, or the aromatic rings are optionally substituted by heterocycloalkyl, OCH2-oxetan-3-yl or O-tetrahydropyran-4-yl, optionally substituted by lower alkyl; X is a bond; Y is a bond or -CH2- R' is hydrogen or lower alkyl, R" is hydrogen, lower alkyl, CF3, lower alkoxy, q is 0, 1, 2 or 3; or to a pharmaceutically suitable acid addition salt 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.

  本发明涉及式化合物 式中 R 是氢或低级烷基； R1 是-(CH2)n-(O)o-杂环烷基或-C(O)-杂环烷基，其中杂环烷基任选被低级烷基、羟基、卤素或-(CH2)p-芳基取代； n 为 0、1 或 2； o 为 0 或 1； p 为 0、1 或 2； R2 是 CF3、环烷基，可选择被低级烷氧基或卤素取代，或者是茚-2-基，或者是杂环烷基，可选择被杂芳基取代、 或芳基或杂芳基，其中芳环可选择被一个或两个取代基取代，这些取代基可选 自低级烷基、卤素、杂芳基、羟基、CF3、OCF3、OCH2CF3、OCH2-环烷基、OCH2C(CH2OH)(CH2Cl)(CH3)低级烷氧基、CH2-低级烷氧基、低级烷基或氰基，或被-C(O)-苯基、-O-苯基、-O-CH2-苯基、苯基或-CH2-苯基取代，其中苯基环可任选被卤素、-C(O)-低级烷基、-C(O)OH 或-C(O)O-低级烷基取代、 或芳香环可任选被杂环烷基、OCH2-氧杂环丁烷-3-基或 O-四氢吡喃-4-基（可任选被低级烷基取代）取代； X 是键； Y 是键或 -CH2- R' 是氢或低级烷基、 R" 是氢、低级烷基、CF3、低级烷氧基、 q 是 0、1、2 或 3； 或其药理上合适的酸加成盐。 现已发现，式 I 的化合物对痕量胺相关受体（TAARs），尤其是 TAAR1 具有良好的亲和力。 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）、应激相关障碍、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、药物滥用和其他疾病、偏头痛、高血压、药物滥用和代谢紊乱，如饮食紊乱、糖尿病、糖尿病并发症、肥胖症、血脂异常、能量消耗和同化紊乱、体温平衡紊乱和失调、睡眠和昼夜节律紊乱以及心血管疾病。
• US9452980B2
  申请人：——

  公开号：US9452980B2

  公开（公告）日：2016-09-27
• [EN] SUBSTITUTED BENZAMIDE DERIVATIVES<br/>[FR] DÉRIVÉS DE BENZAMIDE SUBSTITUÉS
  申请人：HOFFMANN LA ROCHE

  公开号：WO2011076678A1

  公开（公告）日：2011-06-30

  The invention relates to compounds of formula I wherein R is hydrogen or lower alkyl; R1 is -(CH2)n-(O)o-heterocycloalkyl or -C(O)-heterocycloalkyl, wherein the heterocycloalkyl group is optionally substituted by lower alkyl, hydroxy, halogen or by -(CH2)p-aryl; n is 0, 1 or 2; o is 0 or 1; p is 0, 1 or 2; R2 is CF3, cycloalkyl, optionally substituted by lower alkoxy or halogen, or is indan-2-yl, or is heterocycloalkyl, optionally substituted by heteroaryl, or is aryl or heteroaryl, wherein the aromatic rings are optionally substituted by one or two substituents, selected from lower alkyl, halogen, heteroaryl, hydroxy, CF3, OCF3, OCH2CF3, OCH2-cycloalkyl, OCH2C(CH2OH)(CH2C1)(CH3), S-lower alkyl, lower alkoxy, CH2-lower alkoxy, lower alkinyl or cyano, or by-C(O)-phenyl, -O-phenyl, -O- CH2-phenyl, phenyl or -CH2-phenyl, and wherein the phenyl rings may optionally be substituted by halogen, -C(O)-lower alkyl, -C(O)OH or -C(O)O-lower alkyl, or the aromatic rings are optionally substituted by heterocycloalkyl, OCH2-oxetan-3-yl or O-tetrahydropyran-4-yl, optionally substituted by lower alkyl; X is a bond, -NR'-, -CH2NH-, -CHR''-, -(CHR'')q-O-, -O-(CHR'')q- or -(CH2)2-; Y is a bond or -CH2- R' is hydrogen or lower alkyl, R'' is hydrogen, lower alkyl, CF3, lower alkoxy, q is 0, 1, 2 or 3; or to a pharmaceutically suitable acid addition salt 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 Parkinsons disease, neurodegenerative disorders such as Alzheimers 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I的化合物，其中R是氢或较低的烷基；R1是-(CH2)n-(O)o-杂环烷基或-C(O)-杂环烷基，其中杂环烷基基团可选择地被较低的烷基，羟基，卤素或-(CH2)p-芳基取代；n为0、1或2；o为0或1；p为0、1或2；R2为CF3，环烷基，可选择地被较低的烷氧基或卤素取代，或为茚-2-基，或为杂环烷基，可选择地被杂芳基取代，或为芳基或杂芳基，其中芳香环可选择地被来自较低的烷基，卤素，杂芳基，羟基，CF3，OCF3，OCH2CF3，OCH2-环烷基，OCH2C(CH2OH)(CH2C1)(CH3)，S-较低的烷基，较低的烷氧基，CH2-较低的烷氧基，较低的炔基或氰基，或-C(O)-苯基，-O-苯基，-O-CH2-苯基，苯基或-CH2-苯基选择的一个或两个取代基取代，其中苯环可选择地被卤素，-C(O)-较低的烷基，-C(O)OH或-C(O)O-较低的烷基取代，或芳香环可选择地被杂环烷基，OCH2-氧杂环戊烷-3-基或O-四氢吡喃-4-基，可选择地被较低的烷基取代；X为键，-NR'-，-CH2NH-，-CHR''-，-(CHR'')q-O-，-O-(CHR'')q-或-(CH2)2-；Y为键或-CH2-；R'为氢或较低的烷基，R''为氢，较低的烷基，CF3，较低的烷氧基，q为0、1、2或3；或其药学上适宜的酸盐。现已发现，该式I的化合物对痕量胺相关受体（TAARs）具有良好的亲和力，特别是对于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，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，能量消耗和吸收异常，体温稳态异常，睡眠和昼夜节律异常，以及心血管疾病。