N-t-butoxycarbonyl-O-(2'-phenyl)ethyltyramine | 788824-74-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: N-t-butoxycarbonyl-O-(2'-phenyl)ethyltyramine
• 英文别名: tert-butyl N-(1-benzyl-4'-methoxyphenethyl)carbamate；tert-butyl N-[2-[4-(2-phenylethoxy)phenyl]ethyl]carbamate
• CAS: 788824-74-8
• 化学式: C₂₁H₂₇NO₃
• 分子量: 341.45
• InChiKey: UWICZFYDCLEUAB-UHFFFAOYSA-N

物化性质

• 沸点：
  496.1±38.0 °C(Predicted)
• 密度：
  1.072±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  25
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-t-butoxycarbonyl-O-(2'-phenyl)ethyltyramine 在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 以93%的产率得到O-(2'-phenyl)ethyltyramine hydrochloride
  参考文献：
  名称：

  Trace Amine-Associated Receptor Agonists:  Synthesis and Evaluation of Thyronamines and Related Analogues

  摘要：

  We have previously shown that several thyronamines, decarboxylated and deiodinated metabolites of the thyroid hormone, potently activate an orphan G protein-coupled receptor in vitro (TAAR1) and induced hypothermia in vivo on a rapid time scale [Scanlan, T. S.; Suchland, K. L.; Hart, M. E.; Chiellini, G.; Huang, Y.; Kruzich, P. J.; Frascarelli, S.; Crossley, D. A.; Bunzow, J. R.; Ronca-Testoni, S.; Lin, E. T.; Hatton, D.; Zucchi, R.; Grandy, D. K. 3-Iodothyronamine is an endogenous and rapid-acting derivative of thyroid hormone. Nat. Med. 2004, 10 (6), 638-642]. Herein, we report the synthesis of these thyronamines. Additionally, a large number of thyroamine derivatives were synthesized in an effort to understand the molecular basis of TAAR1 activation and hypothermia induction. Several derivatives were found to potently activate both rTAAR1 and mTAAR1 in vitro (compounds 77, 85, 91, and 92). When administered to mice at a 50 mg/kg dose, these derivatives all induced significant hypothermia within 60 min and exhibited a hypothermic induction profile analogous to 3-iodothyronamine (1, T(1)AM) except 91, which proved to be more efficacious. On the basis of this result, a dose-dependent profile for 91 was generated and an ED50 Of 30 mu mol/kg was calculated. Compound 91 proved to be more potent than T(1)AM for TAAR1 activation and exhibits increased potency and efficacy for hypothermia induction. These data further strengthen the pharmacological correlation linking TAAR1 activation by thyronamines and hypothermia induction in mice.

  DOI：

  10.1021/jm0505718
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 碳酸氢钠 、 potassium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 N-t-butoxycarbonyl-O-(2'-phenyl)ethyltyramine
  参考文献：
  名称：

  Trace Amine-Associated Receptor Agonists:  Synthesis and Evaluation of Thyronamines and Related Analogues

  摘要：

  We have previously shown that several thyronamines, decarboxylated and deiodinated metabolites of the thyroid hormone, potently activate an orphan G protein-coupled receptor in vitro (TAAR1) and induced hypothermia in vivo on a rapid time scale [Scanlan, T. S.; Suchland, K. L.; Hart, M. E.; Chiellini, G.; Huang, Y.; Kruzich, P. J.; Frascarelli, S.; Crossley, D. A.; Bunzow, J. R.; Ronca-Testoni, S.; Lin, E. T.; Hatton, D.; Zucchi, R.; Grandy, D. K. 3-Iodothyronamine is an endogenous and rapid-acting derivative of thyroid hormone. Nat. Med. 2004, 10 (6), 638-642]. Herein, we report the synthesis of these thyronamines. Additionally, a large number of thyroamine derivatives were synthesized in an effort to understand the molecular basis of TAAR1 activation and hypothermia induction. Several derivatives were found to potently activate both rTAAR1 and mTAAR1 in vitro (compounds 77, 85, 91, and 92). When administered to mice at a 50 mg/kg dose, these derivatives all induced significant hypothermia within 60 min and exhibited a hypothermic induction profile analogous to 3-iodothyronamine (1, T(1)AM) except 91, which proved to be more efficacious. On the basis of this result, a dose-dependent profile for 91 was generated and an ED50 Of 30 mu mol/kg was calculated. Compound 91 proved to be more potent than T(1)AM for TAAR1 activation and exhibits increased potency and efficacy for hypothermia induction. These data further strengthen the pharmacological correlation linking TAAR1 activation by thyronamines and hypothermia induction in mice.

  DOI：

  10.1021/jm0505718

文献信息

• Thyronamine derivatives and analogs and methods of use thereof
  申请人：Scanlan S. Thomas

  公开号：US20050096485A1

  公开（公告）日：2005-05-05

  Thyronamine derivatives and analogs, methods of using such compounds, and pharmaceutical compositions containing them are disclosed. Methods of preparing such compounds are also disclosed

  本发明揭示了甲状腺胺衍生物和类似物，使用这些化合物的方法，以及含有它们的制药组合物。还揭示了制备这些化合物的方法。
• THYRONAMINE DERIVATIVES AND ANALOGS AND METHODS OF USE THEREOF
  申请人：Scanlan Thomas S.

  公开号：US20090105347A1

  公开（公告）日：2009-04-23

  Thyronamine derivatives and analogs, methods of using such compounds, and pharmaceutical compositions containing them are disclosed. Methods of preparing such compounds are also disclosed

  本发明涉及甲状腺胺衍生物和类似物，使用这些化合物的方法以及包含它们的药物组合物。本发明还揭示了制备这些化合物的方法。
• Development of Photoredox Cross-Electrophile Coupling of Strained Heterocycles with Aryl Bromides Using High-Throughput Experimentation for Library Construction
  作者：Yukiko Mori、Mutsuyo Hayashi、Ryuma Sato、Kuninori Tai、Tsuyoshi Nagase

  DOI：10.1021/acs.orglett.3c01821

  日期：2023.8.4

  cross-coupling reaction of aryl halides with strained aliphatic heterocycles facilitated via a ring-opening reaction. This methodology was found to be applicable to medicinally relevant substrates including Boc-protected strained aliphatic heterocycles and (hetero)aryl bromides and was used for compound library construction via parallel medicinal chemistry. Furthermore, the coupling reactions were shown

  采用微型高通量实验开发了芳基卤化物与张力脂肪族杂环通过开环反应促进的光氧化还原辅助还原交叉偶联反应。该方法被发现适用于医学相关底物，包括 Boc 保护的应变脂肪族杂环和（杂）芳基溴，并用于通过平行药物化学构建化合物库。此外，通过连续流动反应，偶联反应可扩展到克级。还讨论了可能的反应机理。
• Phenoxyacetic acid derivatives, preparation thereof, pharmaceutical compositions comprising them and use
  申请人：TANABE SEIYAKU CO., LTD.

  公开号：EP0325245A1

  公开（公告）日：1989-07-26

  Novel phenoxyacetic acid derivative of the formula: wherein R is a substituted or unsubstituted phenyl group, naphthyl group or a sulfur-containing 5-membered hetero-monocyclic group, R¹, R², R³ and R⁴ are hydrogen atom, a lower alkyl group, a phenyl-­lower alkyl group or phenyl group, R⁵ is hydrogen atom or a lower alkyl group, R⁶ is carboxyl group, a protected carboxyl group, hydroxy group or a di(lower alkyl)-amino group, Ring A is a substituted or unsubstituted phenylene group, m is 0 or 1 and n is an integer of 0 to 5, provided that, when m is 0, (1) at least either one of R¹ to R⁴ is or/are a phenyl-lower alkyl group or phenyl group, (2) at least either one of R¹to R⁴ is or/are a lower alkyl group, and R⁶ is hydroxy group, or (3) all of R¹ to R⁴ are hydrogen atom, and Ring A is a substituted phenylene group, or a pharmaceutically acceptable salt thereof are disclosed. Said derivative (I) and a pharmaceutically aceptable salt thereof have a potent platelet aggregation-inhibiting activity. The derivative (I) is used for the prophylaxis or treatment of thrombotic diseases in warm-blooded animals. The invention includes a variety of prepara­tion methods for the above derivative (I) and pharma­ceutical compositions comprising said derivative (I) in therapeutically effective amounts.

  式中的新型苯氧乙酸衍生物： 其中 R 是取代或未取代的苯基、萘基或含硫五元杂单环基团，R¹、R²、R³ 和 R⁴ 是氢原子、低级烷基、苯基-低级烷基或苯基、R⁵ 是氢原子或低级烷基，R⁶ 是羧基、受保护的羧基、羟基或二(低级烷基)氨基，环 A 是取代或未取代的亚苯基，m 是 0 或 1，n 是 0 至 5 的整数、 条件是，当 m 为 0 时 (1) R¹ 至 R⁴ 中至少有一个是或/是苯基低级烷基或苯基、 (2) R¹ 至 R⁴ 中至少有一个是或/是低级烷基，且 R⁶ 是羟基，或 (3) 所有 R¹ 至 R⁴ 均为氢原子，且环 A 为取代的亚苯基、 或其药学上可接受的盐。所述衍生物（I）及其药学上可接受的盐具有强效的血小板聚集抑制活性。衍生物（I）可用于预防或治疗温血动物的血栓性疾病。本发明包括上述衍生物（I）的各种制备方法和包含治疗有效量的上述衍生物（I）的药物组合物。
• EP1625111A4
  申请人：——

  公开号：EP1625111A4

  公开（公告）日：2007-04-25