tert-butyl 4-[6-(trifluoromethyl)pyridin-3-yl]piperazine-1-carboxylate | 1229627-83-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: tert-butyl 4-[6-(trifluoromethyl)pyridin-3-yl]piperazine-1-carboxylate
• 英文别名: 4-tert-butoxycarbonyl-1-(6-trifluoromethylpyridin-3-yl)piperazine；4-(6-trifluoromethyl-pyridin-3-yl)-piperazine-1-carboxylic acid tert-butyl ester；tert-Butyl 4-(6-(trifluoromethyl)pyridin-3-yl)piperazine-1-carboxylate
• CAS: 1229627-83-1
• 化学式: C₁₅H₂₀F₃N₃O₂
• 分子量: 331.338
• InChiKey: ACNGCYXPDWCXTH-UHFFFAOYSA-N

物化性质

• 沸点：
  400.5±45.0 °C(Predicted)
• 密度：
  1.242±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  45.7
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-[6-(trifluoromethyl)pyridin-3-yl]piperazine-1-carboxylate 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 9.0h， 生成 Nε-acryloyl-L-lysine-4-(6-trifluoromethylpyridin-3-yl)piperazide*2TFA
  参考文献：
  名称：

  N^ε-Acryloyllysine Piperazides as Irreversible Inhibitors of Transglutaminase 2: Synthesis, Structure–Activity Relationships, and Pharmacokinetic Profiling

  摘要：

  Transglutaminase 2 (TGase 2)-catalyzed transamidation represents an important post-translational mechanism for protein modification with implications in physiological and pathophysiological conditions, including fibrotic and neoplastic processes. Consequently, this enzyme is considered a promising target for the diagnosis of and therapy for these diseases. In this study, we report on the synthesis and kinetic characterization of N-acryloyllysine piperazides as irreversible inhibitors of TGase 2. Systematic structural modifications on 54 new compounds were performed with a major focus on fluorine-bearing substituents due to the potential of such compounds to serve as radiotracer candidates for positron emission tomography. The determined inhibitory activities ranged from 100 to 10 000 M-1 s(-1), which resulted in comprehensive structure activity relationships. Structure activity correlations using various substituent parameters accompanied by covalent docking studies provide an advanced understanding of the molecular recognition for this inhibitor class within the active site of TGase 2. Selectivity profiling of selected compounds for other transglutaminases demonstrated an excellent selectivity toward transglutaminase 2. Furthermore, an initial pharmacokinetic profiling of selected inhibitors was performed, including the assessment of potential membrane permeability and liver microsomal stability.

  DOI：

  10.1021/acs.jmedchem.8b00286
• 作为产物：
  描述：

  N-Boc-哌嗪 、 5-溴-2-三氟甲基吡啶 在 tris-(dibenzylideneacetone)dipalladium(0) sodium t-butanolate 、 2-(二环己基膦基)联苯 作用下， 以 甲苯 为溶剂， 反应 0.5h， 生成 tert-butyl 4-[6-(trifluoromethyl)pyridin-3-yl]piperazine-1-carboxylate
  参考文献：
  名称：

  [EN] ANTHELMINTIC AGENTS AND THEIR USE
  [FR] AGENTS ANTHELMINTHIQUES ET LEUR UTILISATION

  摘要：

  这项发明涉及通式（I）的化合物及其盐，通常可用作驱虫剂或作为制备驱虫剂的中间体。这项发明还涉及制备这些化合物的方法，包括这些化合物的药物组合物和试剂盒，利用这些化合物制备药物的用途，以及将这些化合物用于给予需要治疗的动物的治疗。

  公开号：

  WO2010146083A1

文献信息

• ANTHELMINTIC AGENTS AND THEIR USE
  申请人：Chassaing Christophe Pierre Alain

  公开号：US20120094981A1

  公开（公告）日：2012-04-19

  This invention is directed to compounds of the formula (I) and salts therefore that are generally useful as anthelmintic agents or as intermediates in processes for making anthelmintic agents. This invention also is directed to processes for making the compounds of this invention, pharmaceutical compositions and kits comprising the compounds of this invention, uses of the compounds of this invention to make medicaments, and treatments comprising the administration of the compounds of this invention to animals in need of the treatments.

  本发明涉及公式（I）的化合物及其盐，通常用作驱虫剂或作为制备驱虫剂的中间体。本发明还涉及制备本发明化合物的方法，包括本发明化合物的制药组合物和试剂盒，使用本发明化合物制备药物的用途，以及将本发明化合物用于需要治疗的动物的治疗。
• Two Analogues of Fenarimol Show Curative Activity in an Experimental Model of Chagas Disease
  作者：Martine Keenan、Jason H. Chaplin、Paul W. Alexander、Michael J. Abbott、Wayne M. Best、Andrea Khong、Adriana Botero、Catherine Perez、Scott Cornwall、R. Andrew Thompson、Karen L. White、David M. Shackleford、Maria Koltun、Francis C. K. Chiu、Julia Morizzi、Eileen Ryan、Michael Campbell、Thomas W. von Geldern、Ivan Scandale、Eric Chatelain、Susan A. Charman

  DOI：10.1021/jm401610c

  日期：2013.12.27

  Chagas disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), is an increasing threat to global health. Available medicines were introduced over 40 years ago, have undesirable side effects, and give equivocal results of cure in the chronic stage of the disease. We report the development of two compounds, 6 and (S)-7, with PCR-confirmed curative activity in a mouse model of established T. cruzi infection after once daily oral dosing for 20 days at 20 mg/kg 6 and 10 mg/kg (S)-7. Compounds 6 and (S)-7 have potent in vitro activity, are noncytotoxic, show no adverse effects in vivo following repeat dosing, are prepared by a short synthetic route, and have druglike properties suitable for preclinical development.
• Selective GlyT1 Inhibitors: Discovery of [4-(3-Fluoro-5-trifluoromethylpyridin-2-yl)piperazin-1-yl][5-methanesulfonyl-2-((<i>S</i>)-2,2,2-trifluoro-1-methylethoxy)phenyl]methanone (RG1678), a Promising Novel Medicine To Treat Schizophrenia
  作者：Emmanuel Pinard、Alexander Alanine、Daniela Alberati、Markus Bender、Edilio Borroni、Patrick Bourdeaux、Virginie Brom、Serge Burner、Holger Fischer、Dominik Hainzl、Remy Halm、Nicole Hauser、Synese Jolidon、Judith Lengyel、Hans-Peter Marty、Thierry Meyer、Jean-Luc Moreau、Roland Mory、Robert Narquizian、Mathias Nettekoven、Roger D. Norcross、Bernd Puellmann、Philipp Schmid、Sebastien Schmitt、Henri Stalder、Roger Wermuth、Joseph G. Wettstein、Daniel Zimmerli

  DOI：10.1021/jm100210p

  日期：2010.6.24

  The GlyT1 transporter has emerged as a key novel target for the treatment of schizophrenia. Herein, we report on the optimization of the 2-alkoxy-5-methylsulfonebenzoylpiperazine class of GlyT1 inhibitors to improve hERG channel selectivity and brain penetration. This effort culminated in the discovery of compound 10a (RG1678), the first potent and selective GlyT1 inhibitor to have a beneficial effect in schizophrenic patients in a phase II clinical trial.
• US8507474B2
  申请人：——

  公开号：US8507474B2

  公开（公告）日：2013-08-13
• [EN] ANTHELMINTIC AGENTS AND THEIR USE<br/>[FR] AGENTS ANTHELMINTHIQUES ET LEUR UTILISATION
  申请人：INTERVET INT BV

  公开号：WO2010146083A1

  公开（公告）日：2010-12-23

  This invention is directed to compounds of the formula (I) and salts therefore that are generally useful as anthelmintic agents or as intermediates in processes for making anthelmintic agents. This invention also is directed to processes for making the compounds of this invention, pharmaceutical compositions and kits comprising the compounds of this invention, uses of the compounds of this invention to make medicaments, and treatments comprising the administration of the compounds of this invention to animals in need of the treatments.

  这项发明涉及通式（I）的化合物及其盐，通常可用作驱虫剂或作为制备驱虫剂的中间体。这项发明还涉及制备这些化合物的方法，包括这些化合物的药物组合物和试剂盒，利用这些化合物制备药物的用途，以及将这些化合物用于给予需要治疗的动物的治疗。