N-t-butoxycarbonyl-O-triisopropylsilylthyronamine | 788824-52-2

• 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-O-triisopropylsilylthyronamine
• 英文别名: 1,1-Dimethylethyl N-[2-[4-[4-[[tris(1-methylethyl)silyl]oxy]phenoxy]phenyl]ethyl]carbamate；tert-butyl N-[2-[4-[4-tri(propan-2-yl)silyloxyphenoxy]phenyl]ethyl]carbamate
• CAS: 788824-52-2
• 化学式: C₂₈H₄₃NO₄Si
• 分子量: 485.739
• InChiKey: RPULRVJHHOXGHX-UHFFFAOYSA-N

物化性质

• 沸点：
  536.4±45.0 °C(Predicted)
• 密度：
  1.010±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  8.1
• 重原子数：
  34
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  56.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-t-butoxycarbonyl-O-triisopropylsilylthyronamine 在 盐酸 、 四丁基氟化铵 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 生成 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：

  1-溴-4-(三异丙基甲硅烷基氧基)苯 在 吡啶 、 正丁基锂 、 copper diacetate 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 17.0h， 生成 N-t-butoxycarbonyl-O-triisopropylsilylthyronamine
  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

• Biomimetic deiodination of thyroid hormones and iodothyronamines – a structure–activity relationship study
  作者：Santanu Mondal、Govindasamy Mugesh

  DOI：10.1039/c6ob01375a

  日期：——

  ring deiodination of thyroid hormones (THs) and play an important role in maintaining the TH concentration throughout the body. These enzymes also accept the decarboxylated thyroid hormone metabolites, iodothyronamines (TAMs), as substrates for deiodination. Naphthalene-based selenium and/or sulphur-containing small molecules have been shown to mediate the regioselective tyrosyl ring deiodination of

  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。
• Trace Amine-Associated Receptor Agonists:  Synthesis and Evaluation of Thyronamines and Related Analogues
  作者：Matthew E. Hart、Katherine L. Suchland、Motonori Miyakawa、James R. Bunzow、David K. Grandy、Thomas S. Scanlan

  DOI：10.1021/jm0505718

  日期：2006.2.1

  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.