(S)-2,2-dimethyl-4-[(E)-2-(4-nitrophenyl)vinyl]oxazolidine-3-carboxylic acid tert-butyl ester | 1302579-22-1

• 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)-2,2-dimethyl-4-[(E)-2-(4-nitrophenyl)vinyl]oxazolidine-3-carboxylic acid tert-butyl ester
• 英文别名: 1,1-dimethylethyl (S)-2,2-dimethyl-4-[(E)-2-(4-nitrophenyl)ethenyl]-3-oxazolidinecarboxylate；(S)-2,2-dimethyl-4-[(E)-2-(4-nitro-phenyl)-vinyl]-oxazolidine-3-carboxylic acid tert-butyl ester；S-2,2-Dimethyl-4-[(E)-2-(4-nitro-phenyl)-vinyl]-oxazolidine-3-carboxylic acid tert-butyl ester；tert-butyl (4S)-2,2-dimethyl-4-[(E)-2-(4-nitrophenyl)ethenyl]-1,3-oxazolidine-3-carboxylate
• CAS: 1302579-22-1
• 化学式: C₁₈H₂₄N₂O₅
• 分子量: 348.399
• InChiKey: WLIKPKSOCKMSQK-SHQCLWGWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  84.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-2,2-dimethyl-4-[(E)-2-(4-nitrophenyl)vinyl]oxazolidine-3-carboxylic acid tert-butyl ester 在 N-甲基吗啉 、 palladium 10% on activated carbon 、 ammonium formate 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 17.5h， 生成 (S)-4-{2-[4-(4-chloro-benzoylamino)-phenyl]-ethyl}-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Pharmaceutical combination

  摘要：

  本发明涉及一种用于治疗精神分裂症和与双相障碍相关的急性躁狂发作的药物组合，包括对痕量胺相关受体1（TAAR1激动剂）具有活性的化合物和抗精神病药物。该组合可以减少单独使用抗精神病药物时出现的代谢副作用。

  公开号：

  US09132136B2
• 作为产物：
  描述：

  (S)-n-boc-3-氨基-4-羟基丁酸 在 sodium tetrahydroborate 、 正丁基锂 、 草酰氯 、 三氟化硼乙醚 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 17.0h， 生成 (S)-2,2-dimethyl-4-[(E)-2-(4-nitrophenyl)vinyl]oxazolidine-3-carboxylic acid tert-butyl ester 、 1,1-dimethylethyl (S)-2,2-dimethyl-4-[(Z)-2-(4-nitrophenyl)ethenyl]-3-oxazolidinecarboxylate
  参考文献：
  名称：

  Synthesis of a novel series of 2,3,4-trisubstituted oxazolidines designed by isosteric replacement or rigidification of the structure and cytotoxic evaluation

  摘要：

  2,3,4-三取代噁唑啉结构的刚化增强了对LNCaP细胞的活性，而不影响正常细胞增殖。

  DOI：

  10.1039/c4md00136b

文献信息

• PHARMACEUTICAL COMBINATION
  申请人：Hoener Marius

  公开号：US20120028964A1

  公开（公告）日：2012-02-02

  The present invention relates to a pharmaceutical combination for the treatment of schizophrenia and acute manic episodes associated with bipolar disorders, which comprises a compound which is active on a trace amine-associated receptor 1 (TAAR1 agonist) and an antipsychotic drug. This combination can reduce metabolic side effects which appear if using an antipsychotic drug alone.

  本发明涉及一种用于治疗精神分裂症和与双相障碍相关的急性躁狂发作的药物组合，包括对痕量胺相关受体1（TAAR1激动剂）具有活性的化合物和抗精神病药物。该组合可以减少单独使用抗精神病药物时出现的代谢副作用。
• DIHYDROOXAZOL-2-AMINE DERIVATIVES
  申请人：Nettekoven Matthias

  公开号：US20120108609A1

  公开（公告）日：2012-05-03

  The invention relates to compounds of formula wherein R 1 , R 2 , R 3 , R 4 , X, Ar, and are defined herein or 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.

  本发明涉及以下结构的化合物，其中R1、R2、R3、R4、X、Ar和在此处定义，或其药用合适的酸盐。公式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。
• [EN] DIHYDROOXAZOL-2-AMINE DERIVATIVES<br/>[FR] DÉRIVÉS DE DIHYDROOXAZOL-2-AMINE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2012059371A1

  公开（公告）日：2012-05-10

  The invention relates to compounds of formula (I) wherein R1 is hydrogen or lower alkyl; R2 is hydrogen or is heteroaryl, optionally substituted by one or more halogen, lower alkyl, lower alkyl substituted by halogen, lower alkoxy, lower alkoxy substituted by halogen, cyano, S-lower alkyl, S(O)-lower alkyl, S(O)2-lower alkyl, C(O)-lower alkyl or C3-6-cycloalkyl; R3 is hydrogen, halogen, lower alkyl, lower alkyl substituted by halogen, lower alkoxy, lower alkoxy substituted by halogen, cyano, S-lower alkyl, S(O)-lower alkyl, S(O)2-lower alkyl, C(O)-lower alkyl or C3-6-cycloalkyl; R4 is hydrogen or lower alkyl; (A) is phenyl or pyridinyl, wherein the N-atom may be in different positions; X is a bond or CH(CF3)-; Ar is aryl or heteroaryl, optionally substituted by one or more R3; 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.

  该发明涉及公式(I)的化合物，其中R1是氢或较低的烷基；R2是氢或是杂环芳基，可选择地被一个或多个卤素、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、氰基、S-较低烷基、S(O)-较低烷基、S(O)2-较低烷基、C(O)-较低烷基或C3-6-环烷基取代；R3是氢、卤素、较低烷基、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、氰基、S-较低烷基、S(O)-较低烷基、S(O)2-较低烷基、C(O)-较低烷基或C3-6-环烷基；R4是氢或较低烷基；(A)是苯基或吡啶基，其中N原子可能在不同位置；X是键或CH(CF3)-；Ar是芳基或杂环芳基，可选择地被一个或多个R3取代；或其药学上适宜的酸盐。现在发现公式I的化合物对痕量胺相关受体（TAARs）有很好的亲和性，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。
• OXAZOLINE DERIVATIVES
  申请人：Galley Guido

  公开号：US20110112080A1

  公开（公告）日：2011-05-12

  The invention relates to compounds of formula I wherein the definitions of X, R and R 1 are as defined herein. The 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.

  该发明涉及公式I中的化合物，其中X、R和R1的定义如本文所述。公式I中的化合物对痕量胺相关受体（TAARs）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）、与压力相关的障碍、精神分裂症等精神障碍、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。
• Oxazoline derivatives
  申请人：Galley Guido

  公开号：US08354441B2

  公开（公告）日：2013-01-15

  The invention relates to compounds of formula I wherein the definitions of X, R and R1 are as defined herein. The 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.

  本发明涉及公式I的化合物，其中X、R和R1的定义如本文所述。公式I的化合物对微量胺相关受体（TAARs），特别是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）、与压力相关的疾病、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、能量消耗和同化障碍、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。