N-(4-methoxybenzyl)(5,6-dimethyl)benzimidazole | 341941-85-3

• 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: N-(4-methoxybenzyl)(5,6-dimethyl)benzimidazole
• 英文别名: 1-(4-methoxybenzyl)-5,6-dimethyl-1H-benzo[d]imidazole；ZINC31903301；1-(4-methoxybenzyl)-5,6-dimethyl-1H-benzimidazole；1-[(4-methoxyphenyl)methyl]-5,6-dimethylbenzimidazole
• CAS: 341941-85-3
• 化学式: C₁₇H₁₈N₂O
• 分子量: 266.343
• InChiKey: RTEBQWLCBTVKOO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  27
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-(4-methoxybenzyl)(5,6-dimethyl)benzimidazole 在 palladium diacetate 、 copper (I) acetate 、 copper(II) acetate monohydrate 、 cesium pivalate 作用下， 以 1,4-二氧六环 为溶剂， 反应 3.0h， 以63%的产率得到3-methoxy-7,8-dimethyl-11H-isoindolo[2,1-a]benzimidazole
  参考文献：
  名称：

  Intramolecular arylation of benzimidazoles via Pd(II)/Cu(I) catalyzed cross-dehydrogenative coupling

  摘要：

  Electron poor benzimidazole substrates were arylated via an intramolecular cross-dehydrogenative coupling (CDC) reaction. These CDC reactions were catalyzed by a Pd(II)/Cu(I) catalyst system, capable of producing moderate yields on a large library of substrates. The substrate scope consisted of tethered arene-benzimidazoles that upon coupling, produced a fused polycyclic motif. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2014.01.103
• 作为产物：
  描述：

  5,6-二甲基苯并咪唑 、 4-甲氧基溴苄 在 sodium hydride 、 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 N-(4-methoxybenzyl)(5,6-dimethyl)benzimidazole
  参考文献：
  名称：

  The benzimidazole based drugs show good activity against T. gondii but poor activity against its proposed enoyl reductase enzyme target

  摘要：

  The enoyl acyl-carrier protein reductase (ENR) enzyme of the apicomplexan parasite family has been intensely studied for antiparasitic drug design for over a decade, with the most potent inhibitors targeting the NAD(+) bound form of the enzyme. However, the higher affinity for the NADH co-factor over NAD(+) and its availability in the natural environment makes the NADH complex form of ENR an attractive target. Herein, we have examined a benzimidazole family of inhibitors which target the NADH form of Francisella ENR, but despite good efficacy against Toxoplasma gondii, the IC50 for T. gondii ENR is poor, with no inhibitory activity at 1 μM. Moreover similar benzimidazole scaffolds are potent against fungi which lack the ENR enzyme and as such we believe that there may be significant off target effects for this family of inhibitors.

  DOI：

  10.1016/j.bmcl.2013.12.066

文献信息

• A general Pd/Cu-catalyzed C–H heteroarylation of 3-bromoquinolin-2(1H)-ones
  作者：Alexandre Bruneau、Jean-Daniel Brion、Samir Messaoudi、Mouad Alami

  DOI：10.1039/c4ob01610f

  日期：——

  The Pd(OAc)₂/CuI system effectively catalyzes the coupling of 3-bromoquinolin-2(1H)-ones with a series of azoles to give 3-(heteroaryl)quinolin-2(1H)-ones in good yields.

  Pd(OAc)2/CuI系统有效地催化了3-溴喹啉-2(1H)-酮与一系列唑类化合物的偶联反应，产生了3-(杂环芳基)喹啉-2(1H)-酮，收率较高。
• Synthesis and Biological Activity of 3-(Heteroaryl)quinolin-2(1H)-ones Bis-Heterocycles as Potential Inhibitors of the Protein Folding Machinery Hsp90
  作者：Enrique L. Larghi、Alexandre Bruneau、Félix Sauvage、Mouad Alami、Juliette Vergnaud-Gauduchon、Samir Messaoudi

  DOI：10.3390/molecules27020412

  日期：——

  study concerning 6BrCaQ analogues as C-terminal Hsp90 inhibitors, we designed and synthesized a novel series of 3-(heteroaryl)quinolin-2(1H), of types 3, 4, and 5, as a novel class of analogues. A Pd-catalyzed Liebeskind–Srogl cross-coupling was developed as a convenient approach for easy access to complex purine architectures. This series of analogues showed a promising biological effect against MDA-MB231

  在我们关于 6BrCaQ 类似物作为 C 端 Hsp90 抑制剂的 SAR 研究中，我们设计并合成了一系列新型 3-(杂芳基)喹啉-2(1H)，类型为 3、4 和 5，作为一类新型药物的类似物。 Pd 催化的 Liebeskind-Srogl 交叉偶联被开发为一种方便的方法，可以轻松获得复杂的嘌呤结构。该系列类似物对 MDA-MB231 和 PC-3 癌细胞系表现出有希望的生物效应。这项研究确定了最好的化合物 3b (IC50 = 28 µM) 和 4e，它们可显着减少 CDK-1 客户蛋白并稳定 Hsp90 和 Hsp70 的水平，而不触发 HSR 反应。
• Discovery of the First Potent and Selective Inhibitors of Human dCTP Pyrophosphatase 1
  作者：Sabin Llona-Minguez、Andreas Höglund、Sylvain A. Jacques、Lars Johansson、José Manuel Calderón-Montaño、Magnus Claesson、Olga Loseva、Nicholas C. K. Valerie、Thomas Lundbäck、Javier Piedrafita、Giovanni Maga、Emmanuele Crespan、Laurent Meijer、Estefanía Burgos Morón、Pawel Baranczewski、Ann-Louise Hagbjörk、Richard Svensson、Elisee Wiita、Ingrid Almlöf、Torkild Visnes、Fredrik Jeppsson、Kristmundur Sigmundsson、Annika Jenmalm Jensen、Per Artursson、Ann-Sofie Jemth、Pål Stenmark、Ulrika Warpman Berglund、Martin Scobie、Thomas Helleday

  DOI：10.1021/acs.jmedchem.5b01741

  日期：2016.2.11

  The dCTPase pyrophosphatase 1 (dCTPase) regulates the intracellular nucleotide pool through hydrolytic degradation of canonical and noncanonical nucleotide triphosphates (dNTPs). dCTPase is highly expressed in multiple carcinomas and is associated with cancer cell sternness. Here we report on the development of the first potent and selective dCTPase inhibitors that enhance the cytotoxic effect of cytidine analogues in leukemia cells. Boronate 30 displays a promising in vitro ADME profile, including plasma and mouse microsomal half-lives, aqueous solubility, cell permeability and CYP inhibition, deeming it a suitable compound for in vivo studies.
• ENOYL REDUCTASE INHIBITORS WITH ANTIBACTERIAL ACTIVITY
  申请人：JOHNSON Michael

  公开号：US20150246888A1

  公开（公告）日：2015-09-03

  Disclosed are compounds and compositions useful as antibacterials. In particular, disclosed are enoyl reductase (FabI) inhibitors, compositions comprising such compounds, processes for producing such compounds, and methods of using such compounds.
• [EN] ENOYL REDUCTASE INHIBITORS WITH ANTIBACTERIAL ACTIVITY<br/>[FR] INHIBITEURS D'ÉNOYLE RÉDUCTASE AYANT UNE ACTIVITÉ ANTIBACTÉRIENNE
  申请人：UNIV ILLINOIS

  公开号：WO2014043246A1

  公开（公告）日：2014-03-20

  Disclosed are compounds and compositions useful as antibacterials. In particular, disclosed are enoyl reductase (FabI) inhibitors, compositions comprising such compounds, processes for producing such compounds, and methods of using such compounds.