1-(bromomethyl)-2-nitro-4-phenylbenzene

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-(bromomethyl)-2-nitro-4-phenylbenzene
• 英文别名: 4-bromomethyl-3-nitro-biphenyl
• 化学式: C₁₃H₁₀BrNO₂
• 分子量: 292.132
• InChiKey: QZELKFPDHHJIJX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  45.8
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(bromomethyl)-2-nitro-4-phenylbenzene 在 tin(II) chloride dihdyrate 作用下， 以 甲醇 、 乙酸乙酯 、 乙腈 为溶剂， 反应 27.58h， 生成 N3'-[3-(3-amino-biphenyl-4-ylmethyl)-3H-imidazol-4-ylmethyl]-6'-chloro-N2,N2-dimethylbiphenyl-2,3'-diamine
  参考文献：
  名称：

  Dialkylimidazole inhibitors of Trypanosoma cruzi sterol 14α-demethylase as anti-Chagas disease agents

  摘要：

  New dialkylimidazole based sterol 14 alpha-demethylase inhibitors were prepared and tested as potential anti-Trypanosoma cruzi agents. Previous studies had identified compound 2 as the most potent and selective inhibitor against parasite cultures. In addition, animal studies had demonstrated that compound 2 is highly efficacious in the acute model of the disease. However, compound 2 has a high molecular weight and high hydrophobicity, issues addressed here. Systematic modifications were carried out at four positions on the scaffold and several inhibitors were identified which are highly potent (EC50 <1 nM)against T. cruzi in culture. The halogenated derivatives 36j, 36k, and 36p, display excellent activity against T. cruzi amastigotes, with reduced molecular weight and lipophilicity, and exhibit suitable physicochemical properties for an oral drug candidate. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.08.015
• 作为产物：
  描述：

  4-溴-2-硝基甲苯 在 N-溴代丁二酰亚胺(NBS) 、 barium hydroxide octahydrate 、 过氧化苯甲酰 作用下， 以 四氯化碳 、 乙二醇二甲醚 、 水 为溶剂， 反应 0.25h， 生成 1-(bromomethyl)-2-nitro-4-phenylbenzene
  参考文献：
  名称：

  Dialkylimidazole inhibitors of Trypanosoma cruzi sterol 14α-demethylase as anti-Chagas disease agents

  摘要：

  New dialkylimidazole based sterol 14 alpha-demethylase inhibitors were prepared and tested as potential anti-Trypanosoma cruzi agents. Previous studies had identified compound 2 as the most potent and selective inhibitor against parasite cultures. In addition, animal studies had demonstrated that compound 2 is highly efficacious in the acute model of the disease. However, compound 2 has a high molecular weight and high hydrophobicity, issues addressed here. Systematic modifications were carried out at four positions on the scaffold and several inhibitors were identified which are highly potent (EC50 <1 nM)against T. cruzi in culture. The halogenated derivatives 36j, 36k, and 36p, display excellent activity against T. cruzi amastigotes, with reduced molecular weight and lipophilicity, and exhibit suitable physicochemical properties for an oral drug candidate. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.08.015

文献信息

• 2-oxo-1,3,4-trihydroquinazolinyl derivatives and methods of use
  申请人：——

  公开号：US20030229068A1

  公开（公告）日：2003-12-11

  Selected compounds are effective for treatment of diseases, such as cell proliferation or apoptosis mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable derivatives thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving stroke, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

  选定的化合物对于治疗疾病，如细胞增殖或凋亡介导的疾病，具有有效性。该发明涵盖了新颖的化合物、类似物、前药和其药学上可接受的衍生物，药物组合物以及预防和治疗涉及中风、癌症等疾病和其他疾病或病症的方法。该发明还涉及制备这些化合物的方法，以及在这些方法中有用的中间体。
• Structurally Simple Inhibitors of Lanosterol 14α-Demethylase Are Efficacious In a Rodent Model of Acute Chagas Disease
  作者：Praveen Kumar Suryadevara、Srinivas Olepu、Jeffrey W. Lockman、Junko Ohkanda、Mandana Karimi、Christophe L. M. J. Verlinde、James M. Kraus、Jan Schoepe、Wesley C. Van Voorhis、Andrew D. Hamilton、Frederick S. Buckner、Michael H. Gelb

  DOI：10.1021/jm900030h

  日期：2009.6.25

  We report structure-activity studies of a large number of dialkyl imidazoles as inhibitors of Trypanosoma cruzi lanosterol-14 alpha-demethylase (L14DM). The compounds have a simple structure compared to posaconazole, another L14DM inhibitor that is an anti-Chagas drug candidate. Several compounds display potency for killing T cruzi amastigotes in vitro with values of EC50 in the 0.4-10 nM range. Two compounds were selected for efficacy studies in a mouse model of acute Chagas disease. At oral doses of 20-50 mg/kg given after establishment of parasite infection, the compounds reduced parasitemia in the blood to undetectable levels, and analysis of remaining parasites by PCR revealed a lack of parasites in the majority of animals. These dialkyl imidazoles are substantially less expensive to produce than posaconazole and are appropriate for further development toward an anti-Chagas disease clinical candidate.
• Structure–activity relationships of 3,4-dihydro-1H-quinazolin-2-one derivatives as potential CDK5 inhibitors
  作者：Robert M. Rzasa、Matthew R. Kaller、Gang Liu、Ella Magal、Thomas T. Nguyen、Timothy D. Osslund、David Powers、Vincent J. Santora、Vellarkad N. Viswanadhan、Hui-Ling Wang、Xiaoling Xiong、Wenge Zhong、Mark H. Norman

  DOI：10.1016/j.bmc.2007.07.005

  日期：2007.10

  Cyclin-dependent kinase 5 (CDK5) is a serine/threonine kinase that plays a critical role in the early development of the nervous system. Deregulation of CDK5 is believed to contribute to the abnormal phosphorylation of various cellular substrates associated with neurodegenerative disorders such as Alzheimer's disease, amyotrophic lateral sclerosis, and ischemic stroke. Acyclic urea 3 was identified as a potent CDK5 inhibitor and co-crystallographic data of urea 3/CDK2 enzyme were used to design a novel series of 3,4-dihydroquinazolin-2(1H)-ones as CDK5 inhibitors. In this investigation we present our synthetic studies toward this series of compounds and discuss their biological relevance as CDK5 inhibitors. (c) 2007 Elsevier Ltd. All rights reserved.
• 2-OXO-1,3,4-TRIHYDROQUINAZOLINYL DERIVATIVES FOR THE TREATMENT OF CELL PROLIFERATION-RELATED DISORDERS
  申请人：AMGEN INC.

  公开号：EP1507776B1

  公开（公告）日：2007-02-28
• US7119111B2
  申请人：——

  公开号：US7119111B2

  公开（公告）日：2006-10-10