4-(4-methyl-1H-imidazol-1-yl)benzonitrile

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-(4-methyl-1H-imidazol-1-yl)benzonitrile
• 英文别名: 4-(4-Methylimidazol-1-yl)benzonitrile；4-(4-methylimidazol-1-yl)benzonitrile
• 化学式: C₁₁H₉N₃
• 分子量: 183.213
• InChiKey: GJZUHSFKIVFWFX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  41.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-(4-methyl-1H-imidazol-1-yl)benzonitrile 在 lithium aluminium tetrahydride 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 生成 N-(4-(4-methyl-1H-imidazol-1-yl)benzyl)-9H-carbazole-2-carboxamide
  参考文献：
  名称：

  Design, synthesis, and evaluation of novel porcupine inhibitors featuring a fused 3-ring system based on the ‘reversed’ amide scaffold

  摘要：

  The Wnt signaling pathway is an essential signal transduction pathway which leads to the regulation of cellular processes such as proliferation, differentiation and migration. Aberrant Wnt signaling is known to have an association with multiple cancers. Porcupine is an enzyme that catalyses the addition of palmitoleate to a serine residue in Wnt proteins, a process which is required for the secretion of Wnt proteins. Here we report the synthesis and structure-activity-relationship of the novel porcupine inhibitors based on a 'reversed' amide scaffold. The leading compound 53 was as potent as the clinical compound LGK974 in a cell based STF reporter gene assay. Compound 53 potently inhibited the secretion of Wnt3A, therefore was confirmed to be a porcupine inhibitor. Furthermore, compound 53 showed excellent chemical and plasma stabilities. However, the clearance of compound 53 in liver microsomal tests was moderate to high, and the solubility of compound 53 was suboptimal. Collective efforts toward further optimization of this novel tricyclic template to develop better porcupine inhibitors will be subsequently undertaken and reported in due course. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.09.041
• 作为产物：
  描述：

  4-甲基咪唑 、 4-溴苯腈 在 copper(l) iodide 、 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以85%的产率得到4-(4-methyl-1H-imidazol-1-yl)benzonitrile
  参考文献：
  名称：

  Design, synthesis, and evaluation of novel porcupine inhibitors featuring a fused 3-ring system based on the ‘reversed’ amide scaffold

  摘要：

  The Wnt signaling pathway is an essential signal transduction pathway which leads to the regulation of cellular processes such as proliferation, differentiation and migration. Aberrant Wnt signaling is known to have an association with multiple cancers. Porcupine is an enzyme that catalyses the addition of palmitoleate to a serine residue in Wnt proteins, a process which is required for the secretion of Wnt proteins. Here we report the synthesis and structure-activity-relationship of the novel porcupine inhibitors based on a 'reversed' amide scaffold. The leading compound 53 was as potent as the clinical compound LGK974 in a cell based STF reporter gene assay. Compound 53 potently inhibited the secretion of Wnt3A, therefore was confirmed to be a porcupine inhibitor. Furthermore, compound 53 showed excellent chemical and plasma stabilities. However, the clearance of compound 53 in liver microsomal tests was moderate to high, and the solubility of compound 53 was suboptimal. Collective efforts toward further optimization of this novel tricyclic template to develop better porcupine inhibitors will be subsequently undertaken and reported in due course. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.09.041

文献信息

• Anilinotriazoles as potent gamma secretase modulators
  作者：Adriana I. Velter、François P. Bischoff、Didier Berthelot、Michel De Cleyn、Daniel Oehlrich、Libuse Jaroskova、Gregor Macdonald、Garrett Minne、Serge Pieters、Frederik Rombouts、Sven Van Brandt、Yves Van Roosbroeck、Michel Surkyn、Andrés A. Trabanco、Gary Tresadern、Tongfei Wu、Herman Borghys、Marc Mercken、Chantal Masungi、Harrie Gijsen

  DOI：10.1016/j.bmcl.2014.10.024

  日期：2014.12

  The design and synthesis of a novel series of potent gamma secretase modulators is described. Exploration of various spacer groups between the triazole ring and the aromatic appendix in 2 has led to anilinotriazole 28, which combined high in vitro and in vivo potency with an acceptable drug-like profile.

  描述了一系列新型的有效γ分泌酶调节剂的设计和合成。探索三唑环和芳香族附录2之间的各种间隔基团已产生苯胺三唑28，该化合物将体外和体内的高效力与可接受的类药物特性结合在一起。
• FACTOR XA INHIBITORS
  申请人：Zhu Bing-Yan

  公开号：US20090298806A1

  公开（公告）日：2009-12-03

  The present invention is directed to compounds represented by Formula I and pharmaceutically acceptable salts, solvates, hydrates, and prodrugs thereof which are inhibitors of Factor Xa. The present invention is also directed to and intermediates used in making such compounds, pharmaceutical compositions containing such compounds, methods to prevent or treat a number of conditions characterized by undesired thrombosis and methods of inhibiting the coagulation of a blood sample.

  本发明涉及由公式I表示的化合物及其药学上可接受的盐、溶剂化合物、水合物和前药，这些化合物是凝血因子Xa的抑制剂。本发明还涉及制备这些化合物所使用的中间体，含有这些化合物的药物组合物，预防或治疗一系列由不良血栓形成表征的疾病的方法，以及抑制血样的凝血的方法。
• Ullmann-Type N-, S-, and O-Arylation Using a Well-Defined 7-Azaindole-N-oxide (7-AINO)-Based Copper(II) Catalyst: Scope and Application to Drug Synthesis
  作者：Vishal Talukdar、Krishanu Mondal、Pallabi Halder、Parthasarathi Das

  DOI：10.1021/acs.joc.3c02852

  日期：2024.6.7

  well-defined copper(II)-7-azaindole-N-oxide-based catalyst [Cu2II(7-AINO)4] (abbreviated as Cu(II)-7-AINO) has been demonstrated as an efficient catalyst for various Ullmann-type coupling reactions. This easily prepared and cost-effective catalyst facilitates the arylation and heteroarylation of diverse N-, S-, and O-nucleophiles, including azoles, aminoazoles, (hetero)arylthiols, and phenols. Notably

  一种空气稳定、稳健且定义明确的铜（II）-7-氮杂吲哚-N-氧化物基催化剂 [Cu2II（7-AINO）4]（缩写为 Cu（II）-7-AINO）已被证明是各种 Ullmann 型偶联反应的有效催化剂。这种易于制备且经济高效的催化剂有助于各种亲核试剂（包括唑类、氨基唑类、（杂）芳基硫醇和酚类）的芳基化和杂芳基化。值得注意的是，它们还表现出与各种官能团的显著相容性。此外，在这两种情况下，该催化剂对氨基唑类化合物的 –NH 位点和氨基硫酚类化合物的 –SH 位点均表现出显著的选择性，优于 –NH2 位点，增强了其多功能性。利用催化剂的化学选择性和区域选择性，我们已经成功地证明了我们的方法在合成各种药物分子中的适用性。具体来说，使用我们的方案成功合成了 Epirizole 类似物、Nilotinib 和 Vortioxetine。
• US7521470B2
  申请人：——

  公开号：US7521470B2

  公开（公告）日：2009-04-21
• US8153670B2
  申请人：——

  公开号：US8153670B2

  公开（公告）日：2012-04-10