N-t-butoxycarbonyl-thyronamine | 788824-55-5

• 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: N-t-butoxycarbonyl-thyronamine
• 英文别名: N-t-BOC-thyronamine；tert-butyl N-[2-[4-(4-hydroxyphenoxy)phenyl]ethyl]carbamate
• CAS: 788824-55-5
• 化学式: C₁₉H₂₃NO₄
• 分子量: 329.396
• InChiKey: LKHFIFAHHWHBLQ-UHFFFAOYSA-N

物化性质

• 沸点：
  492.4±40.0 °C(Predicted)
• 密度：
  1.151±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  67.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-t-butoxycarbonyl-thyronamine 在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 以100%的产率得到Thyronamine 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：

  4-(三异丙基硅烷基氧基)苯基基硼酸 在 吡啶 、 四丁基氟化铵 、 copper diacetate 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 13.0h， 生成 N-t-butoxycarbonyl-thyronamine
  参考文献：
  名称：

  甲状腺激素和碘甲状腺素胺的仿生去碘化作用–结构-活性关系研究†

  摘要：

  哺乳动物的硒酶碘甲状腺素脱碘酶（DIOs）催化甲状腺激素（THs）的酪氨酰和酚环碘化作用，并在维持全身TH浓度中起重要作用。这些酶还接受脱羧甲状腺激素代谢物碘甲状腺素（TAMs）作为脱碘的底物。已显示基于萘的硒和/或含硫的小分子介导甲状腺激素及其代谢产物的区域选择性酪氨酰环去碘化。在此，我们报道了一系列用于甲状腺激素和碘代乙胺的碘化的周边取代的含硒萘衍生物的结构-活性关系研究。单晶X射线晶体学和77Se NMR光谱研究表明，分子内Se⋯X（X = N，O和S）相互作用在合成模拟物的脱碘酶活性中起重要作用。此外，已观察到萘基硒和/或含硫的合成脱碘酶模拟物对脱羧代谢物TAMs的酪氨酰环脱碘作用比THs慢，这是基于Se⋯I卤素键的强度进行了解释。由TH和TAM组成。

  DOI：

  10.1039/c6ob01375a

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。
• Conformational Flexibility and Halogen Bonding in Thyroid Hormones and Their Metabolites
  作者：Santanu Mondal、Govindasamy Mugesh

  DOI：10.1021/acs.cgd.6b00945

  日期：2016.10.5

  (TAMs) are endogenous thyroid hormone (TH) metabolites, which are proposed to be biosynthesized by decarboxylation of the β-alanine side chain of THs. Iodothyronine deiodinases (DIOs) mediate phenolic and tyrosyl ring deiodinations of thyroid hormones and play an important role in thyroid hormone homeostasis. These enzymes also accept iodothyronamines as substrates for deiodination, but the binding affinities

  碘甲状腺素胺（TAMs）是内源性甲状腺激素（TH）代谢产物，被提议通过THs的β-丙氨酸侧链脱羧来生物合成。碘甲状腺素脱碘酶（DIOs）介导甲状腺激素的酚和酪氨酰环脱碘，并在甲状腺激素稳态中发挥重要作用。这些酶也接受碘代胸腺嘧啶作为脱碘的底物，但TAM与DIO的结合亲和力低于TH。在本文中，我们首次报告了使用单晶X射线研究在各种碘代乙胺中形成卤素键的情况。我们还描述了脱碘后TH和TAM结构发生的构象变化。
• 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。
• WO2007/59039
  申请人：——

  公开号：——

  公开（公告）日：——
• EP1625111A4
  申请人：——

  公开号：EP1625111A4

  公开（公告）日：2007-04-25