3-benzoimidazol-1-ylmethyl-benzonitrile | 562803-57-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 3-benzoimidazol-1-ylmethyl-benzonitrile
• 英文别名: 3-((1H-benzo[d]imidazol-1-yl)methyl)benzonitrile；Benzimidazole,1-M-cyanobenzyl；3-(benzimidazol-1-ylmethyl)benzonitrile
• CAS: 562803-57-0
• 化学式: C₁₅H₁₁N₃
• mdl: MFCD09938703
• 分子量: 233.272
• InChiKey: LXWMENDLAGLVFJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.066
• 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：

  3-benzoimidazol-1-ylmethyl-benzonitrile 在 lithium aluminium tetrahydride 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 18.0h， 生成 N-(3-((1H-benzo[d]imidazol-1-yl)methyl)benzyl)-4-cyano-3-methylbenzamide
  参考文献：
  名称：

  Discovery of Highly Potent Benzimidazole Derivatives as Indoleamine 2,3-Dioxygenase-1 (IDO1) Inhibitors: From Structure-Based Virtual Screening to in Vivo Pharmacodynamic Activity

  摘要：

  In this study, a successful medicinal chemistry campaign that exploited virtual, biophysical, and biological investigations led to the identification of a novel class of IDO1 inhibitors based on a benzimidazole substructure. This family of compounds is endowed with an extensive bonding network in the protein active site, including the interaction with pocket C, a region not commonly exploited by previously reported IDO1 inhibitors. The tight packing of selected compounds within the enzyme contributes to the strong binding interaction with IDO1, to the inhibitory potency at the low nanomolar level in several tumoral settings, and to the selectivity toward IDO1 over TDO and CYPs. Notably, a significant reduction of L-Kyn levels in plasma, together with a potent effect on abrogating immunosuppressive properties of MDSC-like cells isolated from patients affected by pancreatic ductal adenocarcinoma, was observed, pointing to this class of molecules as a valuable template for boosting the antitumor immune system.

  DOI：

  10.1021/acs.jmedchem.9b01809
• 作为产物：
  描述：

  苯并咪唑 、 3-氰基苄基溴 在 potassium hydroxide 作用下， 以 乙醇 为溶剂， 反应 8.0h， 以87%的产率得到3-benzoimidazol-1-ylmethyl-benzonitrile
  参考文献：
  名称：

  间氰基苄基取代的苯并咪唑鎓盐：合成、表征、晶体结构和碳酸酐酶、α-糖苷酶、丁酰胆碱酯酶和乙酰胆碱酯酶抑制特性

  摘要：

  间氰基苄基取代的 N-杂环卡宾 (NHC) 前体是通过一系列 N-(烷基)苯并咪唑鎓与 3-溴甲基-苄腈反应合成的。这些苯并咪唑盐通过使用 1H NMR、13C NMR、FTIR 光谱和元素分析技术进行表征。2f 和 2g 配合物的分子和晶体结构是通过使用单晶 X 射线衍射方法获得的。这些新型 NHC 前体的衍生物是 α-糖苷酶 (AG)、胞质碳酸酐酶 I 和 II 异构体（hCA I 和 II）、丁酰胆碱酯酶 (BChE) 和乙酰胆碱酯酶 (AChE) 的有效抑制剂，其 Ki 值范围为AG 为 1.01–2.12 nM，hCA I 为 189.56–402.44 nM，hCA II 为 112.50–277.37 nM，AChE 为 95.45–352.58 nM，B 为 132.91–571.18 nM。在过去的几年里，

  DOI：

  10.1002/ardp.201800029

文献信息

• <i>meta</i>-Cyanobenzyl substituted benzimidazolium salts: Synthesis, characterization, crystal structure and carbonic anhydrase, α-glycosidase, butyrylcholinesterase, and acetylcholinesterase inhibitory properties
  作者：Ferhat Türker、Duygu Barut Celepci、Aydın Aktaş、Parham Taslimi、Yetkin Gök、Muhittin Aygün、İlhami Gülçin

  DOI：10.1002/ardp.201800029

  日期：2018.7

  single‐crystal X‐ray diffraction method. The derivatives of these novel NHC precursors were effective inhibitors of α‐glycosidase (AG), the cytosolic carbonic anhydrase I and II isoforms (hCA I and II), butyrylcholinesterase (BChE), and acetylcholinesterase (AChE) with Ki values in the range of 1.01–2.12 nM for AG, 189.56–402.44 nM for hCA I, 112.50–277.37 nM for hCA II, 95.45–352.58 nM for AChE, and 132.91–571

  间氰基苄基取代的 N-杂环卡宾 (NHC) 前体是通过一系列 N-(烷基)苯并咪唑鎓与 3-溴甲基-苄腈反应合成的。这些苯并咪唑盐通过使用 1H NMR、13C NMR、FTIR 光谱和元素分析技术进行表征。2f 和 2g 配合物的分子和晶体结构是通过使用单晶 X 射线衍射方法获得的。这些新型 NHC 前体的衍生物是 α-糖苷酶 (AG)、胞质碳酸酐酶 I 和 II 异构体（hCA I 和 II）、丁酰胆碱酯酶 (BChE) 和乙酰胆碱酯酶 (AChE) 的有效抑制剂，其 Ki 值范围为AG 为 1.01–2.12 nM，hCA I 为 189.56–402.44 nM，hCA II 为 112.50–277.37 nM，AChE 为 95.45–352.58 nM，B 为 132.91–571.18 nM。在过去的几年里，
• Synthesis and characterization of nitrile functionalized silver(I)-N-heterocyclic carbene complexes: DNA binding, cleavage studies, antibacterial properties and mosquitocidal activity against the dengue vector, Aedes albopictus
  作者：Patrick O. Asekunowo、Rosenani A. Haque、Mohd. R. Razali、Silas W. Avicor、Mustafa F.F. Wajidi

  DOI：10.1016/j.ejmech.2018.03.029

  日期：2018.4

  compound, 8b, could effectively intercalate into DNA to form 8b–DNA complex which shows a better binding ability for DNA (Kb = 3.627 × 106) than the complexes 5b–7b (2.177 × 106, 8.672 × 105 and 6.665 × 105, respectively). Nuclease activity of the complexes on plasmid DNA and Aedes albopictus genomic DNA was time-dependent, although minimal. The complexes were larvicidal to the mosquito, with 5b, 6b and

  合成了四种基于苯并咪唑的腈基官能化单核-Ag （I）-N-杂环卡宾和双核-Ag（I）-N-杂环卡宾（Ag（I）-NHC）六氟磷酸盐配合物（5b - 8b）使相应的六氟磷酸盐（1b – 4b）与Ag 2 O在乙腈中反应。这些化合物的特征在于1 H NMR，13 C NMR，IR，紫外可见光谱技术，元素分析和摩尔电导率。另外，通过单晶X射线衍射技术对8b进行结构表征。初步体外对所有化合物针对两种标准细菌进行了抗菌评估；革兰氏阳性（金黄色葡萄球菌）和革兰氏阴性（大肠杆菌）菌株。大多数Ag（I）–NHC复合物（5b – 8b）表现出中等至良好的抗菌活性，MIC值在12.5–100μg/ mL的范围内。特别是，化合物8b表现出有希望的抗金黄色葡萄球菌活性，且MIC值低（12.5μg/ mL）。但是，所有六氟磷酸盐（1b - 4b）对细菌菌株均无活性。初步的互动调查显示，活性最高的化合物8b能有效地插入DNA，以形成图8b
• A structure–Permeability study of small drug-like molecules
  作者：Thomas Fichert、Mehran Yazdanian、John R. Proudfoot

  DOI：10.1016/s0960-894x(02)01035-1

  日期：2003.2

  A systematic structure permeability relationship study on a set of small drug-like molecules with log D values in the range -2.5 to 3 and carrying a diverse Arran of functionality reveals that the compounds with log D>0 and <3 are highly permeable. Surprisingly. several tetrazole derivatives were found to be substrates for efflux pump(s). (C) 2003 Elsevier Science Ltd. All rights reserved.
• Discovery of Highly Potent Benzimidazole Derivatives as Indoleamine 2,3-Dioxygenase-1 (IDO1) Inhibitors: From Structure-Based Virtual Screening to <i>in Vivo</i> Pharmacodynamic Activity
  作者：Marta Serafini、Enza Torre、Silvio Aprile、Erika Del Grosso、Alessandro Gesù、Alessia Griglio、Giorgia Colombo、Cristina Travelli、Salvatore Paiella、Annalisa Adamo、Elena Orecchini、Alice Coletti、Maria Teresa Pallotta、Stefano Ugel、Alberto Massarotti、Tracey Pirali、Silvia Fallarini

  DOI：10.1021/acs.jmedchem.9b01809

  日期：2020.3.26

  In this study, a successful medicinal chemistry campaign that exploited virtual, biophysical, and biological investigations led to the identification of a novel class of IDO1 inhibitors based on a benzimidazole substructure. This family of compounds is endowed with an extensive bonding network in the protein active site, including the interaction with pocket C, a region not commonly exploited by previously reported IDO1 inhibitors. The tight packing of selected compounds within the enzyme contributes to the strong binding interaction with IDO1, to the inhibitory potency at the low nanomolar level in several tumoral settings, and to the selectivity toward IDO1 over TDO and CYPs. Notably, a significant reduction of L-Kyn levels in plasma, together with a potent effect on abrogating immunosuppressive properties of MDSC-like cells isolated from patients affected by pancreatic ductal adenocarcinoma, was observed, pointing to this class of molecules as a valuable template for boosting the antitumor immune system.