tert-butyl-(4-(2-(4-fluorophenyl)-2-oxoethyl)pyridin-2-yl)(3-methylbutan-2-yl)carbamate | 1012305-49-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: tert-butyl-(4-(2-(4-fluorophenyl)-2-oxoethyl)pyridin-2-yl)(3-methylbutan-2-yl)carbamate
• 英文别名: 2-(2-(Boc(3-methylbutan-2-yl)amino)pyridin-4-yl)-1-(4-fluorophenyl)ethanone；tert-butyl N-[4-[2-(4-fluorophenyl)-2-oxoethyl]pyridin-2-yl]-N-(3-methylbutan-2-yl)carbamate
• CAS: 1012305-49-5
• 化学式: C₂₃H₂₉FN₂O₃
• 分子量: 400.493
• InChiKey: KNBNUGWJSBBLJH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 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：

  tert-butyl-(4-(2-(4-fluorophenyl)-2-oxoethyl)pyridin-2-yl)(3-methylbutan-2-yl)carbamate 在 盐酸 、 palladium 10% on activated carbon 、 氢气 、 溶剂黄146 、 sodium nitrite 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 4-(4-fluorophenyl)-5-(2-(3-methylbutan-2-ylamino)pyridin-4-yl)-1,3-dihydroimidazol-2-thione
  参考文献：
  名称：

  An optimized and versatile synthesis to pyridinylimidazole-type p38α mitogen activated protein kinase inhibitors

  摘要：

  报道了一种针对制备强效吡啶基咪唑类p38α MAP激酶抑制剂的优化和多样化合成方法。

  DOI：

  10.1039/c5ob01505g
• 作为产物：
  描述：

  2-溴-4-甲基吡啶 在 4-二甲氨基吡啶 、 tris-(dibenzylideneacetone)dipalladium(0) 、 sodium hexamethyldisilazane 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 为溶剂， 生成 tert-butyl-(4-(2-(4-fluorophenyl)-2-oxoethyl)pyridin-2-yl)(3-methylbutan-2-yl)carbamate
  参考文献：
  名称：

  An optimized and versatile synthesis to pyridinylimidazole-type p38α mitogen activated protein kinase inhibitors

  摘要：

  报道了一种针对制备强效吡啶基咪唑类p38α MAP激酶抑制剂的优化和多样化合成方法。

  DOI：

  10.1039/c5ob01505g

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。
• From 2-Alkylsulfanylimidazoles to 2-Alkylimidazoles: An Approach towards Metabolically More Stable p38α MAP Kinase Inhibitors
  作者：Fabian Heider、Urs Haun、Eva Döring、Mark Kudolo、Catharina Sessler、Wolfgang Albrecht、Stefan Laufer、Pierre Koch

  DOI：10.3390/molecules22101729

  日期：——

  microsomes, respectively. They display a 4-fold increased binding affinity towards the target kinase as well as similar in vitro potency and ex vivo efficacy relative to their 2-alkylsulfanylimidazole counterparts ML3403 and LN950. For example, 2-alkylimidazole 2, the analog of LN950, inhibits both the p38α MAP kinase as well as the LPS-stimulated tumor necrosis factor-α release from human whole blood in

  体外和体内代谢研究表明，2-烷基硫基咪唑 ML3403 (4-(5-(4-fluorophenyl)-2-(methylthio)-1H-imidazol-4-yl)-N-(1-phenylethyl)pyridin-2 -胺）快速氧化成亚砜。替换存在于两种有效的 p38α 丝裂原活化蛋白 (MAP) 激酶抑制剂 ML3403 和 LN950 中的硫原子（2-（（5-（4-氟苯基）-4-（2-（（3-甲基丁-2-基）氨基)吡啶-4-基)-1H-咪唑-2-基)硫代)乙-1-醇)分别产生具有显着改善的代谢稳定性的2-烷基咪唑衍生物1和2。2-烷基咪唑类似物 1 和 2 在与人肝微粒体孵育 4 小时后分别显示 20% 和 10% 的生物转化。与 2-烷基硫基咪唑对应物 ML3403 和 LN950 相比，它们对靶激酶的结合亲和力增加了 4 倍，并且具有相似的体外效力和离体功效。例如，LN950 的类似物
• 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.