4-(6-氟吡啶-2-基)哌嗪-1-羧酸叔丁酯 | 1016167-46-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 4-(6-氟吡啶-2-基)哌嗪-1-羧酸叔丁酯
• 英文名称: 4-(6-fluoropyridin-2-yl)piperazine-1-carboxylic acid t-butyl ester
• 英文别名: 4-tert-butoxycarbonyl-1-(6-fluoropyridin-2-yl)piperazine；tert-butyl 4-(6-fluoropyridin-2-yl)piperazine-1-carboxylate
• CAS: 1016167-46-6
• 化学式: C₁₄H₂₀FN₃O₂
• 分子量: 281.33
• InChiKey: AESFVWLAXBKWOI-UHFFFAOYSA-N

物化性质

• 沸点：
  407.6±45.0 °C(Predicted)
• 密度：
  1.185±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  45.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(6-氟吡啶-2-基)哌嗪-1-羧酸叔丁酯 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 1-(6-氟-2-吡啶基)哌嗪
  参考文献：
  名称：

  转谷氨酰胺酶2 18 F标签不可逆抑制剂的开发，作为在细胞和组织中定量表达谱的放射学工具

  摘要：

  转谷氨酰胺酶2（TGase 2）的转酰胺酶活性被认为对包括纤维化和赘生性组织生长在内的几种病理生理过程很重要，而在健康细胞中，这种酶功能主要是潜伏的。能够高度敏感地检测TGase 2的方法，例如基于放射性标记的基于活性的探针的应用，将支持对该酶在各种疾病中的功能的探索。在这种情况下，放射合成和详述体外一个的radiopharmacological评价18 F-标记Ñ ε报道了丙烯酰赖氨酸哌嗪。对于分离的蛋白质，细胞裂解物和活细胞，由于不可逆的共价键形成，在色谱和电泳分离后，通过薄层板和聚丙烯酰胺凝胶的放射自显影对放射性示踪剂-TGase 2复合物进行了稳健而简便的检测。通过使用这种放射性示踪剂，首次通过组织切片的放射自显影获得了可激活的TGase 2在小鼠器官和选定的肿瘤中的表达谱的定量数据。

  DOI：

  10.1021/acs.jmedchem.1c00096
• 作为产物：
  描述：

  2,6-二氟吡啶 、 N-Boc-哌嗪 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以45%的产率得到4-(6-氟吡啶-2-基)哌嗪-1-羧酸叔丁酯
  参考文献：
  名称：

  转谷氨酰胺酶2 18 F标签不可逆抑制剂的开发，作为在细胞和组织中定量表达谱的放射学工具

  摘要：

  转谷氨酰胺酶2（TGase 2）的转酰胺酶活性被认为对包括纤维化和赘生性组织生长在内的几种病理生理过程很重要，而在健康细胞中，这种酶功能主要是潜伏的。能够高度敏感地检测TGase 2的方法，例如基于放射性标记的基于活性的探针的应用，将支持对该酶在各种疾病中的功能的探索。在这种情况下，放射合成和详述体外一个的radiopharmacological评价18 F-标记Ñ ε报道了丙烯酰赖氨酸哌嗪。对于分离的蛋白质，细胞裂解物和活细胞，由于不可逆的共价键形成，在色谱和电泳分离后，通过薄层板和聚丙烯酰胺凝胶的放射自显影对放射性示踪剂-TGase 2复合物进行了稳健而简便的检测。通过使用这种放射性示踪剂，首次通过组织切片的放射自显影获得了可激活的TGase 2在小鼠器官和选定的肿瘤中的表达谱的定量数据。

  DOI：

  10.1021/acs.jmedchem.1c00096

文献信息

• [EN] HETEROCYCLIC COMPOUNDS AS IMAGING PROBES OF TAU PATHOLOGY<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES UTILISÉS COMME SONDES D'IMAGERIE DE PATHOLOGIE TAU
  申请人：GE HEALTHCARE LTD

  公开号：WO2013090497A1

  公开（公告）日：2013-06-20

  Pyridazinone compounds of Formula I: (I) wherein: R' is alkyl or Ar, optionally substituted with at least one alkyl, halo¬ gen, hydroxyl, alkoxy, haloalkoxy, acid, ester, amino, nitro, amide, or alkoxyhalo; 2 R is independently alkyi, alkynyl, ester, amino, amide, acid, aryl, heteroaryl, aminoalkyl, -C(=0)alkyl, -C(=0)aryl, -C(=0)heteroaryl, -C(=0)heterocycloalkyl, - C(=0)heterocycloalkylAr, -C(=0)(CH2)nhalo, -C(=0)(CH2)nheterocyclyl, or -SC^Ar, optionally substituted with at least one alkyi, alkylhalo, halogen, nitro, aryl, heteroaryl, or heteroaryl(CH2)nhalo; R 3 and R4 are independently hydrogen, alkyi, alkenyl, alkynyl, aryl, heteroaryl; Ar is an aryl, heteroaryl, cycloalkyl, heterocycloalkyl group; n is an integer from 0-10; or a radiolabeled derivative thereof. The compounds are useful as imaging probes of Tau pathology in Alzheimer's disease are described. Compositions and methods of making such compounds are also described.

  Formula I中的吡啶嗪酮化合物：（I），其中：R'是烷基或Ar，可选择地取代为至少一个烷基，卤素，羟基，烷氧基，卤代烷氧基，酸，酯，氨基，硝基，酰胺，或烷氧基卤代；2 R独立地是烷基，炔基，酯，氨基，酰胺，酸，芳基，杂环芳基，氨基烷基，-C(=0)烷基，-C(=0)芳基，-C(=0)杂环芳基，-C(=0)杂环烷基，-C(=0)杂环烷基Ar，-C(=0)(CH2)n卤代，-C(=0)(CH2)n杂环基，或-SC^Ar，可选择地取代为至少一个烷基，烷基卤代，卤素，硝基，芳基，杂环芳基，或杂环芳基(CH2)n卤代；R3和R4独立地是氢，烷基，烯基，炔基，芳基，杂环芳基；Ar是芳基，杂环芳基，环烷基，杂环烷基基团；n是0-10之间的整数；或其放射标记衍生物。所述化合物可用作阿尔茨海默病中Tau病理的成像探针。还描述了制备这种化合物的组成物和方法。
• HETEROCYCLIC COMPOUNDS AS IMAGING PROBES OF TAU PATHOLOGY
  申请人：GE HEALTHCARE LIMITED

  公开号：US20150004100A1

  公开（公告）日：2015-01-01

  Pyridazinone compounds of Formula I: (I) wherein: R′ is alkyl or Ar, optionally substituted with at least one alkyl, halogen, hydroxyl, alkoxy, haloalkoxy, acid, ester, amino, nitro, amide, or alkoxyhalo; 2 R is independently alkyi, alkynyl, ester, amino, amide, acid, aryl, heteroaryl, aminoalkyl, —C(=0)alkyl, —C(=0)aryl, —C(=0)heteroaryl, —C(=0)heterocycloalkyl, —C(=0)heterocycloalkylAr, —C(=0)(CH 2 ) n halo, —C(═O)(CH 2 )nheterocyclyl, or —SĈAr, optionally substituted with at least one alkyi, alkylhalo, halogen, nitro, aryl, heteroaryl, or heteroaryl(CH 2 )nhalo; R 3 and R 4 are independently hydrogen, alkyi, alkenyl, alkynyl, aryl, heteroaryl; Ar is an aryl, heteroaryl, cycloalkyl, heterocycloalkyl group; n is an integer from 0-10; or a radiolabeled derivative thereof. The compounds are useful as imaging probes of Tau pathology in Alzheimer's disease are described. Compositions and methods of making such compounds are also described.

  公式I中的吡啶并酮化合物：(I) 其中：R′是烷基或Ar，可选地被至少一种烷基，卤素，羟基，烷氧基，卤代烷氧基，酸，酯，氨基，硝基，酰胺或烷氧卤代基取代；2R独立地是烷基，炔基，酯，氨基，酰胺，酸，芳基，杂芳基，氨基烷基，-C（= 0）烷基，-C（= 0）芳基，-C（= 0）杂芳基，-C（= 0）杂环烷基，-C（= 0）杂环烷基Ar，-C（= 0）（CH2）n卤代基，-C（═O）（CH2）nheterocyclyl或-SĈAr，可选地被至少一种烷基，烷基卤代基，卤素，硝基，芳基，杂芳基或杂芳基（CH2）n卤代基取代；R3和R4独立地是氢，烷基，烯基，炔基，芳基，杂芳基；Ar是芳基，杂芳基，环烷基，杂环烷基基团；n是0-10的整数；或其放射性标记衍生物。这些化合物可用作阿尔茨海默病中Tau病理学的成像探针。还描述了制备这种化合物的组合物和方法。
• [EN] HETEROCYCLIC GLP-1 AGONISTS<br/>[FR] AGONISTES HÉTÉROCYCLIQUES DE GLP-1
  申请人：GASHERBRUM BIO INC

  公开号：WO2022078407A1

  公开（公告）日：2022-04-21

  This disclosure relates to GLP-1 agonists of Formula (I): including pharmaceutically acceptable salts and solvates thereof, and pharmaceutical compositions including the same.

  本公开涉及公式（I）的GLP-1激动剂：包括其药学上可接受的盐和溶剂，以及包括其的制药组合物。
• <i>N</i>^ε-Acryloyllysine Piperazides as Irreversible Inhibitors of Transglutaminase 2: Synthesis, Structure–Activity Relationships, and Pharmacokinetic Profiling
  作者：Robert Wodtke、Christoph Hauser、Gloria Ruiz-Gómez、Elisabeth Jäckel、David Bauer、Martin Lohse、Alan Wong、Johanna Pufe、Friedrich-Alexander Ludwig、Steffen Fischer、Sandra Hauser、Dieter Greif、M. Teresa Pisabarro、Jens Pietzsch、Markus Pietsch、Reik Löser

  DOI：10.1021/acs.jmedchem.8b00286

  日期：2018.5.24

  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.
• Synthesis, Radiofluorination, and In Vitro Evaluation of Pyrazolo[1,5-<i>a</i>]pyridine-Based Dopamine D₄ Receptor Ligands: Discovery of an Inverse Agonist Radioligand for PET
  作者：Olaf Prante、Rainer Tietze、Carsten Hocke、Stefan Löber、Harald Hübner、Torsten Kuwert、Peter Gmeiner

  DOI：10.1021/jm701375u

  日期：2008.3.1

  A series of fluoro-substituted analogs structurally derived from the aminomethyl-substituted pyrazolo[1,5-a]pyridine lead compounds 9 (FAUC 113) and 10 (FAUC 213) were synthesized and evaluated as high-affinity D(4) receptor (D(4)R) ligands (3a-3h, K(i) = 1.3-28 nM). The para-fluoroethoxy-substituted derivatives 3f and 3h revealed an outstanding D(4) subtype selectivity of more than 3 orders of magnitude over both congeners D(2) and D(3) combined with inverse agonism at D(4)R. The corresponding (18)F-labeled radioligands revealed high serum stability in vitro and log P values of 2-3. In vitro rat brain autoradiography showed specific binding of [(18)F]3h in distinct brain regions, including the gyrus dentate of the hippocampus, that were inhibited by both eticlopride (65-80%) and the selective D(4)R antagonist 10 (78-93%). The observed binding pattern was mainly consistent with the known D(4)R distribution in the rat brain. Thus, [(18)F]3h (FAUC F41) represents a potential radioligand for studying the D(4)R in vivo by positron emission tomography (PET).