2-(2-(benzyl(Boc)amino)pyridin-4-yl)-1-(4-fluorophenyl)ethanone | 1012305-46-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-(2-(benzyl(Boc)amino)pyridin-4-yl)-1-(4-fluorophenyl)ethanone
• 英文别名: tert-butyl N-benzyl-N-(4-(2-(4-fluorophenyl)-2-oxoethyl)pyridin-2-yl)carbamate；tert-Butyl N-benzyl-N-[4-(4-fluorobenzoylmethyl)-2-pyridyl]carbamate；tert-butyl N-benzyl-N-[4-[2-(4-fluorophenyl)-2-oxoethyl]pyridin-2-yl]carbamate
• CAS: 1012305-46-2
• 化学式: C₂₅H₂₅FN₂O₃
• 分子量: 420.484
• InChiKey: PBZJCSDLPMDMEB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  59.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(2-(benzyl(Boc)amino)pyridin-4-yl)-1-(4-fluorophenyl)ethanone 在 selenium(IV) oxide 、 溶剂黄146 作用下， 反应 4.5h， 以51%的产率得到1-(2-(benzylamino)pyridin-4-yl)-2-(4-fluorophenyl)ethan-1,2-dione
  参考文献：
  名称：

  Pyridinylquinoxalines and Pyridinylpyridopyrazines as Lead Compounds for Novel p38α Mitogen-Activated Protein Kinase Inhibitors

  摘要：

  Various substituted 2(3)-(4-fluorophenyl)-3(2)-(pyridin-4-yl)quinoxatines and 2(3)-(4-fluorophenyl)3(2)-(pyridin-4-yl)pyridopyrazines were synthesized as novel p38 alpha MAP kinase inhibitors via different short synthetic strategies with high variation possibilities. The formation of the quinoxaline/pyridopyrazine core was achieved from alpha-cliketones and o-phenylenodiamines/alpha-diaminopyridines under microwave irradiation. Introduction of an amino moiety at the pyridine C2 position of the 2(3)-(4-fluorophenyl)-3(2)-(pyridin-4-yl)quinoxalines led to compounds showing potent enzyme inhibition down to the double-digit nanomolar range (6f; IC50 = 81 nM). Replacement of the quinoxaline core with pyrido[2,3-b]pyrazine gave compound 9e with superior p38 alpha MAP kinase inhibition (IC50 = 38 nM).

  DOI：

  10.1021/jm901392x
• 作为产物：
  描述：

  2-(苯甲酰氨基)-4-甲基吡啶 在 sodium hexamethyldisilazane 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 叔丁醇 为溶剂， 生成 2-(2-(benzyl(Boc)amino)pyridin-4-yl)-1-(4-fluorophenyl)ethanone
  参考文献：
  名称：

  Imidazopyrimidines, potent inhibitors of p38 MAP kinase

  摘要：

  The MAP kinase p38 is implicated in the release of the pro-inflammatory cytokines TNF-alpha and IL-1beta. Inhibition of cytokine release may be a useful treatment for inflammatory conditions such as rheumatoid arthritis and Crohn's disease. A novel series of imidazopyrimidines have been discovered that potently inhibit p38 and suppress the production of TNF-alpha in vivo. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)01020-x

文献信息

• KINASE MODULATORS FOR THE TREATMENT OF CANCER
  申请人：Synovo GmbH

  公开号：US20170313661A1

  公开（公告）日：2017-11-02

  A method of treating cancer in which a compound that inhibits the expression, production or release of IL-10 by immune cells is combined with a compound that stimulates the production of IL-12 when given in combination with, or in the presence of TNFa. Said method is effective when provided in addition to standard therapies, notably chemotherapy using cytotoxic drugs and other forms of immune therapy including therapeutic vaccines.

  一种治疗癌症的方法，其中抑制免疫细胞表达、产生或释放IL-10的化合物与在与TNFa联合给予或存在的情况下刺激IL-12产生的化合物结合。所述方法在提供标准疗法的基础上有效，特别是包括使用细胞毒性药物的化疗和其他形式的免疫疗法，包括治疗性疫苗。
• 2-SULFANYL-SUBSTITUTED IMIDAZOLE DERIVATIVES AND THEIR USE AS CYTOKINE INHIBITORS
  申请人：Burnet Michael

  公开号：US20090270462A1

  公开（公告）日：2009-10-29

  The invention relates to 2-thio-substituted imidazole derivatives of the Formula I, and to methods of use thereof.

  这项发明涉及到式I的2-硫代咪唑衍生物，以及其使用方法。
• Towards the improvement of the synthesis of novel 4(5)-aryl-5(4)-heteroaryl-2-thio-substituted imidazoles and their p38 MAP kinase inhibitory activity
  作者：Stefan Laufer、Pierre Koch

  DOI：10.1039/b717605h

  日期：——

  A series of 2-alkylsulfanyl-4-(4-fluorophenyl)-5-(2-aminopyridin-4-yl)-substituted imidazoles was prepared and interaction possibilities of the 2-thioether moiety with phosphate/ribose binding pockets of p38 MAP kinase were investigated. Introduction of the alkyl/benzyl amino function at the pyridine moiety was carried out via nucleophilic substitution or via palladium catalyzed aryl-C-N-bond formation

  制备了一系列的2-烷基硫烷基-4-（4-氟苯基）-5-（2-氨基吡啶-4-基）取代的咪唑，并且将2-硫醚部分与p38 MAP激酶的磷酸/核糖结合口袋相互作用的可能性被调查了。通过亲核取代或通过钯催化的芳基-CN-键形成在吡啶部分引入烷基/苄基氨基官能团。
• Targeting the Ribose and Phosphate Binding Site of p38 Mitogen-Activated Protein (MAP) Kinase: Synthesis and Biological Testing of 2-Alkylsulfanyl-, 4(5)-Aryl-, 5(4)-Heteroaryl-Substituted Imidazoles
  作者：Pierre Koch、Christiane Bäuerlein、Hartmut Jank、Stefan Laufer

  DOI：10.1021/jm800373t

  日期：2008.9.25

  Three series of substituted 2-alkylsulfanyl-4-(4-fluorophenyl)imidazoles, 5-pyridinyl-, 1-methyl-5-pyridinyl-, and 5-(2-aminopyridin-4-yl)-imidazoles, were prepared and tested for their ability to inhibit p38 MAP kinase and TNF-alpha release. These compounds were prepared by using different synthetic routes. They were tested by applying a nonradioactive p38 MAP kinase assay and by measurement of TNF-a release in human whole blood. Potent inhibitors (IC(50)values in the low nanomolar range, as low as 2 nM in the enzyme assay and 37 nM in the human whole blood test) were identified by variation of substituents at the imidazole-C2-thio position as well as at the 2-aminopyridinyl functionality. In contrast to other known kinase inhibitors, these novel imidazole derivatives with the substituents at the imidazole-C2-thio position may interact with the ribose as well as with the phosphate binding site of the p38 MAP kinase.
• US8143294B2
  申请人：——

  公开号：US8143294B2

  公开（公告）日：2012-03-27