N-t-butoxycarbonyl-O-(m,m-dimethylbenzyl)tyramine | 788824-78-2

• 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-(m,m-dimethylbenzyl)tyramine
• 英文别名: tert-butyl N-[2-[4-[(3,5-dimethylphenyl)methoxy]phenyl]ethyl]carbamate
• CAS: 788824-78-2
• 化学式: C₂₂H₂₉NO₃
• 分子量: 355.477
• InChiKey: GNPQQZNNRNXRQZ-UHFFFAOYSA-N

物化性质

• 沸点：
  502.5±38.0 °C(Predicted)
• 密度：
  1.063±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 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-(m,m-dimethylbenzyl)tyramine 在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 以86%的产率得到O-(m,m-dimethylbenzyl)tyramine 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-(m,m-dimethylbenzyl)tyramine
  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 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。
• US7355079B2
  申请人：——

  公开号：US7355079B2

  公开（公告）日：2008-04-08
• US7321065B2
  申请人：——

  公开号：US7321065B2

  公开（公告）日：2008-01-22
• US7339079B2
  申请人：——

  公开号：US7339079B2

  公开（公告）日：2008-03-04
• 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.