tert-butyl (3-tert-butyl-1H-pyrazol-5-yl)methylcarbamate | 1254717-17-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: tert-butyl (3-tert-butyl-1H-pyrazol-5-yl)methylcarbamate
• 英文别名: tert-butyl N-[(3-tert-butyl-1H-pyrazol-5-yl)methyl]carbamate
• CAS: 1254717-17-3
• 化学式: C₁₃H₂₃N₃O₂
• 分子量: 253.345
• InChiKey: NNYIZNVOHNJSRR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  67
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl (3-tert-butyl-1H-pyrazol-5-yl)methylcarbamate 在 吡啶 、 copper diacetate 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 48.0h， 生成 (3-tert-butyl-1-(3-chlorophenyl)-1H-pyrazol-5-yl)methanamine
  参考文献：
  名称：

  Pyrazole C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as potent TRPV1 antagonists

  摘要：

  A series of 1-substituted 3-(t-butyl/trifluoromethyl)pyrazole C-region analogues of 2-(3-fluoro-4-methyl-sulfonamidophenyl) propanamides were investigated for hTRPV1 antagonism. The structure activity relationship indicated that the 3-chlorophenyl group at the 1-position of pyrazole was the optimized hydrophobic group for antagonistic potency and the activity was stereospecific to the S-configuration, providing exceptionally potent antagonists 13S and 16S with K-i(CAP) = 0.1 nM. Particularly significant, 13S exhibited antagonism selective for capsaicin and NADA and not for low pH or elevated temperature. Both compounds also proved to be very potent antagonists for rTRPV1, blocking in vivo the hypothermic action of capsaicin, consistent with their in vitro mechanism. The docking study of compounds 13S and 16S in our hTRPV1 homology model indicated that the binding modes differed somewhat, with that of 13S more closely resembling that of GRT12360. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.08.020
• 作为产物：
  描述：

  三甲基乙酰基丙酮酸乙酯 在 lithium aluminium tetrahydride 、 盐酸肼 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 为溶剂， 反应 9.0h， 生成 tert-butyl (3-tert-butyl-1H-pyrazol-5-yl)methylcarbamate
  参考文献：
  名称：

  Pyrazole C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as potent TRPV1 antagonists

  摘要：

  A series of 1-substituted 3-(t-butyl/trifluoromethyl)pyrazole C-region analogues of 2-(3-fluoro-4-methyl-sulfonamidophenyl) propanamides were investigated for hTRPV1 antagonism. The structure activity relationship indicated that the 3-chlorophenyl group at the 1-position of pyrazole was the optimized hydrophobic group for antagonistic potency and the activity was stereospecific to the S-configuration, providing exceptionally potent antagonists 13S and 16S with K-i(CAP) = 0.1 nM. Particularly significant, 13S exhibited antagonism selective for capsaicin and NADA and not for low pH or elevated temperature. Both compounds also proved to be very potent antagonists for rTRPV1, blocking in vivo the hypothermic action of capsaicin, consistent with their in vitro mechanism. The docking study of compounds 13S and 16S in our hTRPV1 homology model indicated that the binding modes differed somewhat, with that of 13S more closely resembling that of GRT12360. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.08.020

文献信息

• [EN] SUBSTITUTED AROMATIC CARBOXAMIDE AND UREA DERIVATIVES AS VANILLOID RECEPTOR LIGANDS<br/>[FR] DÉRIVÉS DE CARBOXAMIDE AROMATIQUE ET D'URÉE SUBSTITUÉS EN TANT QUE LIGANDS DU RÉCEPTEUR VANILLOÏDE
  申请人：GRUENENTHAL GMBH

  公开号：WO2010127855A1

  公开（公告）日：2010-11-11

  The invention relates to substituted aromatic carboxamide and urea derivatives, to processes for the preparation thereof, to pharmaceutical compositions containing these compounds and also to the use of these compounds for preparing pharmaceutical compositions (formula (I)).

  这项发明涉及取代芳香族羧酰胺和脲衍生物，以及其制备方法，含有这些化合物的药物组合物，以及利用这些化合物制备药物组合物的用途（式（I））。
• [EN] SUBSTITUTED PYRAZOLYL-BASED CARBOXAMIDE AND UREA DERIVATIVES BEARING A PHENYL MOIETY SUBSTITUTED WITH AN O-CONTAINING GROUP AS VANILLOID RECEPTOR LIGANDS<br/>[FR] DÉRIVÉS DE CARBOXAMIDE ET D'URÉE À BASE DE PYRAZOLYLE SUBSTITUÉ PORTANT UN FRAGMENT PHÉNYLE REMPLACÉ PAR UN GROUPE CONTENANT O COMME LIGANDS DES RÉCEPTEURS VANILLOÏDES
  申请人：GRUENENTHAL GMBH

  公开号：WO2013068461A1

  公开（公告）日：2013-05-16

  The invention relates to substituted pyrazolyl-based carboxamide and urea derivatives of formula (Q) as vanilloid receptor ligands, to pharmaceutical compositions containing these compounds and also to these compounds for use in the treatment and/or prophylaxis of pain and further diseases and/or disorders.

  这项发明涉及以式(Q)的取代吡唑基羧酰胺和脲衍生物作为辣椒素受体配体，以及含有这些化合物的药物组合物，还涉及这些化合物用于治疗和/或预防疼痛以及其他疾病和/或紊乱。
• Substituted Phenylureas and Phenylamides as Vanilloid Receptor Ligands
  申请人：FRANK Robert

  公开号：US20120258946A1

  公开（公告）日：2012-10-11

  Substituted phenylureas and phenylamides, processes for their preparation, pharmaceutical compositions containing these compounds, and the use of these compounds for preparing pharmaceutical compositions.

  取代苯基脲和苯基酰胺，其制备过程，含有这些化合物的制药组合物以及使用这些化合物制备制药组合物的用途。
• Substituted phenylureas and phenylamides as vanilloid receptor ligands
  申请人：Frank Robert

  公开号：US08946204B2

  公开（公告）日：2015-02-03

  Substituted phenylureas and phenylamides, processes for their preparation, pharmaceutical compositions containing these compounds, and the use of these compounds for preparing pharmaceutical compositions.

  取代苯脲和苯酰胺，其制备方法，含有这些化合物的药物组合物以及使用这些化合物制备药物组合物。
• Substituted Aromatic Carboxamide and Urea Derivatives as Vanilloid Receptor Ligands
  申请人：FRANK Robert

  公开号：US20110003795A1

  公开（公告）日：2011-01-06

  The invention relates to substituted aromatic carboxamide and urea derivatives, to processes for the preparation thereof, to pharmaceutical compositions containing these compounds and also to the use of these compounds for preparing pharmaceutical compositions.

  该发明涉及取代芳香族羧酰胺和脲衍生物，其制备过程，含有这些化合物的药物组合物以及利用这些化合物制备药物组合物的用途。