(R)-4-(benzothiazol-2-ylsulfanylmethyl)-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester | 1043500-77-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: (R)-4-(benzothiazol-2-ylsulfanylmethyl)-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl (R)-4-[(benzo[d]thiazol-2-ylthio)methyl]-2,2-dimethyloxazolidine-3-carboxylate；(R)-4-(benzothiazol-2-ylsulfanyl-methyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester；tert-butyl (4R)-4-(1,3-benzothiazol-2-ylsulfanylmethyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate
• CAS: 1043500-77-1
• 化学式: C₁₈H₂₄N₂O₃S₂
• 分子量: 380.532
• InChiKey: OLHGZOXMHHKSPC-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  105
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (R)-4-(benzothiazol-2-ylsulfanylmethyl)-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester 在 2H₃N*2H⁽¹⁺⁾*4H₂O*Mo₇O₂₄^(2-) 、 双氧水 作用下， 以 甲醇 、 水 为溶剂， 以88%的产率得到(R)-4-(benzothiazole-2-sulfonylmethyl)-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  产生立体多样性：α-氨基酸构件的非对映选择性氟化和高度非对映选择性差向异构化

  摘要：

  实现了N -Boc（R）-和（S）-2,2-二甲基-4-（（芳基磺酰基）甲基）恶唑烷的非对映选择性氟化和在含氟碳原子α处向砜的非对映选择性差向异构化。对于苯并噻唑基砜，两个反应的非对映选择性都非常好，可以从一个手性前体获得两个对映体纯的非对映异构体。为了证明其合成用途，将苯并噻唑基砜通过亚磺酸盐转化为非对映体纯的（S，S）-和（R，S）-苄基砜，并将其转化为氨基酸。为了理解非对映选择性，进行了DFT分析。

  DOI：

  10.1021/acs.orglett.8b01358
• 作为产物：
  描述：

  2-(tert-butoxycarbonylamino)-3-hydroxypropionic acid methyl ester 在 lithium aluminium tetrahydride 、 偶氮二甲酸二异丙酯 、 三氟化硼乙醚 、 三苯基膦 作用下， 以 四氢呋喃 、 丙酮 为溶剂， 反应 9.5h， 生成 (R)-4-(benzothiazol-2-ylsulfanylmethyl)-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  产生立体多样性：α-氨基酸构件的非对映选择性氟化和高度非对映选择性差向异构化

  摘要：

  实现了N -Boc（R）-和（S）-2,2-二甲基-4-（（芳基磺酰基）甲基）恶唑烷的非对映选择性氟化和在含氟碳原子α处向砜的非对映选择性差向异构化。对于苯并噻唑基砜，两个反应的非对映选择性都非常好，可以从一个手性前体获得两个对映体纯的非对映异构体。为了证明其合成用途，将苯并噻唑基砜通过亚磺酸盐转化为非对映体纯的（S，S）-和（R，S）-苄基砜，并将其转化为氨基酸。为了理解非对映选择性，进行了DFT分析。

  DOI：

  10.1021/acs.orglett.8b01358

文献信息

• 4,5-DIHYDRO-OXAZOL-2YL DERIVATIVES
  申请人：Galley Guido

  公开号：US20100029589A1

  公开（公告）日：2010-02-04

  The invention relates to compounds of formula I wherein R 1 , R 2 , X, Y, and n are defined in the specification and to pharmaceutically acceptable acid addition salts thereof. The invention also provides pharmaceutical compositions and methods of manufacture of such compounds. The compounds are useful for the treatment of diseases related to the biological function of the trace amine associated receptors, which diseases are depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder, stress-related disorders, psychotic disorders, schizophrenia, neurological diseases, Parkinson's disease, neurodegenerative disorders, Alzheimer's disease, epilepsy, migraine, substance abuse and 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.

  该发明涉及公式I的化合物，其中R1、R2、X、Y和n在规范中定义，并且其药学上可接受的酸盐。该发明还提供了制备这种化合物的药物组合物和方法。这些化合物可用于治疗与痕量胺相关受体的生物功能相关的疾病，这些疾病包括抑郁症、焦虑症、躁郁症、注意缺陷多动障碍、与压力有关的疾病、精神疾病、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、物质滥用和代谢紊乱、进食障碍、糖尿病、糖尿病并发症、肥胖症、脂质代谢异常、能量消耗和吸收异常、体温稳态异常、睡眠和昼夜节律异常、心血管疾病。
• Discovery and Characterization of 2-Aminooxazolines as Highly Potent, Selective, and Orally Active TAAR1 Agonists
  作者：Guido Galley、Angélica Beurier、Guillaume Décoret、Annick Goergler、Roman Hutter、Susanne Mohr、Axel Pähler、Philipp Schmid、Dietrich Türck、Robert Unger、Katrin Groebke Zbinden、Marius C. Hoener、Roger D. Norcross

  DOI：10.1021/acsmedchemlett.5b00449

  日期：2016.2.11

  ligands. Starting from a known adrenergic compound 1, structural modifications were made to obtain highly potent and selective TAAR1 ligands such as 12 (RO5166017), 18 (RO5256390), 36 (RO5203648), and 48 (RO5263397). These compounds exhibit drug-like physicochemical properties, have good oral bioavailability, and display in vivo activity in a variety of animal models relevant for psychiatric diseases

  发现2-氨基恶唑啉是TAAR1配体的新型结构类别。从已知的肾上腺素化合物1开始，进行了结构修饰，以获得高效且选择性的TAAR1配体，例如12（RO5166017），18（RO5256390），36（RO5203648）和48（RO5263397）。这些化合物表现出类似药物的理化性质，具有良好的口服生物利用度，并且在与精神疾病和成瘾有关的多种动物模型中显示出体内活性。
• 2-Aminooxazolines as TAAR1 ligands
  申请人：Galley Guido

  公开号：US20080261920A1

  公开（公告）日：2008-10-23

  The invention relates to compounds of formula I wherein X, Y, R 1 , R 2 , and n are as defined herein or to a pharmaceutically suitable acid addition salt thereof. The invention also relates to pharmaceutical compositions containing such compounds and methods for the treatment of diseases related to the biological function of the trace amine associated receptors, which diseases include depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder, stress-related disorders, psychotic disorders, schizophrenia, neurological diseases, Parkinson's disease, neurodegenerative disorders, Alzheimer's disease, epilepsy, migraine, substance abuse and 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.

  本发明涉及化合物I的公式，其中X，Y，R1，R2和n如本文所定义，或其药学上适宜的酸加盐。本发明还涉及含有这种化合物的制药组合物和治疗与微量胺相关受体的生物学功能相关的疾病的方法，这些疾病包括抑郁症、焦虑症、双相情感障碍、注意力缺陷多动障碍、压力相关障碍、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、物质滥用和代谢性疾病、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。
• 2-AMINOOXAZOLINES AS TAAR1 LIGANDS
  申请人：Galley Guido

  公开号：US20100120864A1

  公开（公告）日：2010-05-13

  The invention relates to compounds of formula I wherein X, Y, R 1 , R 2 , and n are as defined herein or to a pharmaceutically suitable acid addition salt thereof. The invention also relates to pharmaceutical compositions containing such compounds and methods for the treatment of diseases related to the biological function of the trace amine associated receptors, which diseases include depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder, stress-related disorders, psychotic disorders, schizophrenia, neurological diseases, Parkinson's disease, neurodegenerative disorders, Alzheimer's disease, epilepsy, migraine, substance abuse and 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X，Y，R1，R2和n如本文所定义，或其药学适宜的酸加盐。本发明还涉及含有此类化合物的制药组合物，以及用于治疗与微量胺相关受体的生物学功能相关的疾病的方法，这些疾病包括抑郁症，焦虑症，双相情感障碍，注意力缺陷多动障碍，应激相关障碍，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，物质滥用和代谢性疾病，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，睡眠和生物钟节律障碍以及心血管疾病。
• 4,5-dihydro-oxazol-2YL derivatives
  申请人：Hoffmann-La Roche Inc.

  公开号：US08242153B2

  公开（公告）日：2012-08-14

  The invention relates to compounds of formula I wherein R1, R2, X, Y, and n are defined in the specification and to pharmaceutically acceptable acid addition salts thereof. The invention also provides pharmaceutical compositions and methods of manufacture of such compounds. The compounds are useful for the treatment of diseases related to the biological function of the trace amine associated receptors, which diseases are depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder, stress-related disorders, psychotic disorders, schizophrenia, neurological diseases, Parkinson's disease, neurodegenerative disorders, Alzheimer's disease, epilepsy, migraine, substance abuse and 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R1、R2、X、Y和n在规范中定义，并且其药学上可接受的酸盐。本发明还提供了制备这种化合物的制药组合物和方法。这些化合物对于治疗与微量胺相关受体的生物功能相关的疾病非常有用，这些疾病包括抑郁症、焦虑症、双相情感障碍、注意力缺陷多动障碍、压力相关疾病、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、物质滥用和代谢性疾病、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、体温稳态障碍和睡眠和昼夜节律障碍以及心血管疾病。