(S)-4-(3,4-dichlorophenyl)-4,5-dihydrooxazol-2-ylamine | 1043491-54-8

• 物质功能分类: 医药中间体 - 杂环化合物 - 嘧啶类化合物
• 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)-4-(3,4-dichlorophenyl)-4,5-dihydrooxazol-2-ylamine
• 英文别名: (S)-4-(3,4-dichlorophenyl)-4,5-dihydro-1,3-oxazol-2-amine；(S)-4-(3,4-Dichlorophenyl)-4,5-dihydrooxazol-2-amine；(4S)-4-(3,4-dichlorophenyl)-4,5-dihydro-1,3-oxazol-2-amine
• CAS: 1043491-54-8
• 化学式: C₉H₈Cl₂N₂O
• 分子量: 231.081
• InChiKey: HGGPGNSCBBAGJN-MRVPVSSYSA-N

物化性质

• 沸点：
  351.5±52.0 °C(Predicted)
• 密度：
  1.57±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 储存条件：
  | 2-8°C |

制备方法与用途

RO5203648 是一种针对 TAAR1（微量胺相关受体 1）的高效且高度选择性的部分激动剂，表现出极高的亲和力。它为神经精神治疗领域开辟了新的研究方向。

反应信息

• 作为产物：
  描述：

  4-(3,4-dichlorophenyl)-4,5-dihydro-1,3-oxazol-2-amine 以 乙醇 、 正庚烷 为溶剂， 生成 (S)-4-(3,4-dichlorophenyl)-4,5-dihydrooxazol-2-ylamine
  参考文献：
  名称：

  WO2008/92785

  摘要：

  公开号：

文献信息

• [EN] OXAZOLINE PSEUDODIMERS, PHARMACEUTICAL COMPOSITIONS AND THE USE THEREOF<br/>[FR] PSEUDODIMÈRES D'OXAZOLINE, COMPOSITIONS PHARMACEUTIQUES ET UTILISATION CORRESPONDANTES
  申请人：PURDUE PHARMA LP

  公开号：WO2017192858A1

  公开（公告）日：2017-11-09

  The present disclosure is directed to oxazoline mono- and hetero-pseudodimer compounds, such as compounds of Formula (I) or pharmaceutically acceptable salts or solvates thereof: These compounds are useful for treating pain. The present disclosure also relates to pharmaceutical compositions comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of Formula (I) or (II) or a pharmaceutically acceptable salt or solvate thereof

  本公开涉及噁唑啉单聚体和异聚体化合物，例如公式(I)的化合物或其药用可接受盐或溶剂：这些化合物可用于治疗疼痛。本公开还涉及包括药用可接受载体和公式(I)或(II)的化合物或其药用可接受盐或溶剂的治疗有效量的药物组合物
• 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。
• Methods of administering a trace amine-associated receptor 1 (TAAR1) agonist to patients having the minor allele of the single nucleotide polymorphism rs2237457
  申请人：Northwestern University

  公开号：US10098893B2

  公开（公告）日：2018-10-16

  Disclosed are methods and kits for diagnosing, prognosing, and treating patients having psychiatric disorders. The methods may include assessing whether a patient has a treatment resistant psychiatric disorder or assessing whether the patient is likely to develop a treatment resistant psychiatric disorder. The methods may include detecting genetic markers such as the single nucleotide polymorphism (SNP) in genes present in a genomic nucleic acid sample from the patient, and/or receiving, as a caregiver, the results of tests indicating whether the genetic markers are present in the genomic nucleic acid sample from the patient. The methods may include administering treatment to the patient, for example, based on the detected genetic markers, and administering treatment may include administering new antipsychotic drugs (APDs) that are trace amine-associated receptor 1 (TAAR1) agonists.

  所公开的是用于诊断、预后和治疗精神障碍患者的方法和试剂盒。这些方法可包括评估患者是否患有抗药性精神障碍，或评估患者是否有可能患上抗药性精神障碍。这些方法可包括检测患者基因组核酸样本中存在的遗传标记，如基因中的单核苷酸多态性（SNP），和/或作为护理者接收表明患者基因组核酸样本中是否存在遗传标记的检测结果。这些方法可包括对患者进行治疗，例如，根据检测到的遗传标记进行治疗，治疗可包括使用新的抗精神病药物（APDs），这些药物是痕量胺相关受体 1（TAAR1）激动剂。