1-(azidomethyl)-3-(bromomethyl)benzene | 1144106-66-0

• 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-(azidomethyl)-3-(bromomethyl)benzene
• CAS: 1144106-66-0
• 化学式: C₈H₈BrN₃
• 分子量: 226.076
• InChiKey: WQLCVHUOVJSXJW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  14.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(azidomethyl)-3-(bromomethyl)benzene 在 potassium carbonate 、 三苯基膦 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 11.5h， 生成 N-[{3-(N-4-methoxybenzyl-N-methylaminomethyl)phenyl}methyl]formamide
  参考文献：
  名称：

  A series of structurally simple chloroquine chemosensitizing dibemethin derivatives that inhibit chloroquine transport by PfCRT

  摘要：

  A series of 12 new dibemethin (N-benzyl-N-methyl-1-phenylmethanamine) derivatives bearing an Naminomethyl group attached to the one phenyl ring and an H, CI, OCH3 or N(CH3)(2) group on the other have been synthesized. These compounds all showed strong chloroquine chemosensitizing activity, comparable to verapamil, when present at 1 mu M in an in vitro culture of the chloroquine-resistant W2 strain of the human malaria parasite, Plasmodium falciparum. Their N-formylated derivatives also exhibited resistance-reversing activity, but only at substantially higher IC10 concentrations. A number of the dibemethin derivatives were shown to inhibit chloroquine transport via the parasite's 'chloroquine resistance transporter' (PfCRT) in a Xenopus laevis oocyte expression system. The reduced resistance-reversing activity of the formylated compounds relative to their free amine counterparts can probably be ascribed to two factors: decreased accumulation of the formylated dibemethins within the parasite's internal digestive vacuole (believed to be the site of action of chloroquine), and a reduced ability to inhibit PfCRT. The resistance-reversing activity of the compounds described here demonstrates that the amino group need not be attached to the two aromatic rings via a three or four carbon chain as has been suggested by previous QSAR studies. These compounds may be useful as potential side chains for attaching to a 4,7-dichloroquinoline group in order to generate new resistance-reversing chloroquine analogues with inherent antimalarial activity. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.02.026
• 作为产物：
  描述：

  间二溴苄 在 sodium azide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以0.53 g的产率得到1-(azidomethyl)-3-(bromomethyl)benzene
  参考文献：
  名称：

  Molecular construction of HIV-gp120 discontinuous epitope mimics by assembly of cyclic peptides on an orthogonal alkyne functionalized TAC-scaffold

  摘要：

  使用直角炔基化的TAC支架用于构建含有不同肽环的生物活性gp120蛋白类似物的分子。

  DOI：

  10.1039/c5ob02014j

文献信息

• Conjugated antimicrobial agents
  申请人：Technion Research & Development Foundation Limited

  公开号：US09149536B2

  公开（公告）日：2015-10-06

  Provided herein are antimicrobial conjugates of two antibiotic agents, exhibiting improved activity also against resistant bacteria, compared to each of the agents separately or their mixture, and having substantially no resistance emerged thereagainst, as well as processes for preparation the same, compositions containing the same, and uses thereof in medical treatments against pathogenic microorganisms. The disclosed antimicrobial conjugates are composed of aminoglycosides and non-ribosomal active antibiotics. Some of the antimicrobial conjugates are prepared via “click” chemistry.

  本文提供了两种抗生素的抗菌结合物，展现出对抗耐药细菌的改善活性，相比单独使用每种抗生素或它们的混合物，并且基本上没有产生抗性，以及制备这些结合物的过程、含有这些结合物的组合物，以及在医疗治疗中对抗病原微生物的用途。所披露的抗菌结合物由氨基糖苷类和非核糖体活性抗生素组成。其中一些抗菌结合物是通过“click”化学方法制备的。
• Procaspase-3 Activation as an Anti-Cancer Strategy: Structure−Activity Relationship of Procaspase-Activating Compound 1 (PAC-1) and Its Cellular Co-Localization with Caspase-3
  作者：Quinn P. Peterson、Danny C. Hsu、David R. Goode、Chris J. Novotny、Ryan K. Totten、Paul J. Hergenrother

  DOI：10.1021/jm900722z

  日期：2009.9.24

  A goal of personalized medicine as applied to oncology is to identify compounds that exploit a defined molecular defect in a cancerous cell. A compound called procaspase-activating compound I (PAC-1) was reported that enhances the activity of procaspase-3 in vitro and induces apoptotic death in cancer cells in culture and in mouse xenograft models. Experimental evidence indicates that PAC-1 activates procaspase-3 in vitro through chelation of inhibitory zinc ions. Described herein is the synthesis and biological activity of a family of PAC-1 derivatives where key functional groups have been systematically altered. Analysis of these compounds reveals a strong correlation between the in vitro procaspase-3 activating effect and their ability to induce death in cancer cells in culture. Importantly, we also show that a fluorescently labeled version of PAC-1 co-localizes with sites of caspase-3 activity in cancer cells. The data presented herein further bolster the hypothesis that PAC-1 induces apoptosis in cancer cells through the direct activation of procaspase-3, has implications for the design and discovery of next-generation procaspase-3 activating compounds, and sheds light on the anti-apoptotic role of cellular zinc.
• 4-Aminoquinoline Antimalarials Containing a Benzylmethylpyridylmethylamine Group Are Active against Drug Resistant <i>Plasmodium falciparum</i> and Exhibit Oral Activity in Mice
  作者：Mukesh C. Joshi、John Okombo、Samkele Nsumiwa、Jeffrey Ndove、Dale Taylor、Lubbe Wiesner、Roger Hunter、Kelly Chibale、Timothy J. Egan

  DOI：10.1021/acs.jmedchem.7b01537

  日期：2017.12.28

  Emergence of drug resistant Plasmodium falciparum including artemisinin-tolerant parasites highlights the need for new antimalarials. We have previously shown that dibemequines, 4-amino-7-chloroquinolines with dibenzylmethylamine (dibemethin) side chains, are efficacious. In this study, analogues in which the terminal phenyl group of the dibemethin was replaced with a 2-pyridyl group and in which the 4-amino-7-chloroquinoline was either maintained or replaced with a 4-aminoquinoline-7-carbonitrile were synthesized in an effort to improve druglikeness. These compounds exhibited significantly improved solubility and decreased lipophilicity and were potent against chloroquine-sensitive (NF54) and -resistant (Dd2 and 7G8) P. falciparum strains with 5/6 having IC50 < 100 nM against the NF54 strain. All inhibited both,beta-hematin (synthetic hemozoin) formation and hemozoin formation in the parasite. Parasitemia was reduced by over 90% in P. berghei infected mice in 3/6 derivatives following oral dosing at 4 X 30 mg/kg, with microsomal metabolic stability data suggesting that this could be attributed to highly active metabolites.
• Design, Synthesis, and Evaluation of Novel Fluoroquinolone−Aminoglycoside Hybrid Antibiotics
  作者：Varvara Pokrovskaya、Valery Belakhov、Mariana Hainrichson、Sima Yaron、Timor Baasov

  DOI：10.1021/jm900028n

  日期：2009.4.23

  A series of new hybrid structures containing fluoroquinolone (ciprofloxacin) and aminoglycoside (neomycin) antibiotics linked via 1,2,3-triazole moiety were designed and synthesized, and their antibacterial activities were determined against both Gram-negative and Gram-positive bacteria, including resistant strains. The nature of spacers in both the ciprofloxacin and neomycin parts greatly influenced the antibacterial activity. The majority of hybrids was significantly more potent than the parent neomycin and overcame most prevalent types of resistance associated with aminoglycosides. Selected hybrids inhibited bacterial protein synthesis with the potencies similar to or better than that of neomycin and were up to 32-fold more potent inhibitors than ciprofloxacin for the fluoroquinolone targets, DNA gyrase and toposiomerase IV, indicating a balanced dual mode of action. Significant delay of resistance formation was observed in both E. coli and B. subtilis to the treatment with ciprofloxacin-neomycin hybrid in comparison to that of each drug separately or their 1: 1 mixture.
• A series of structurally simple chloroquine chemosensitizing dibemethin derivatives that inhibit chloroquine transport by PfCRT
  作者：Vincent K. Zishiri、Roger Hunter、Peter J. Smith、Dale Taylor、Robert Summers、Kiaran Kirk、Rowena E. Martin、Timothy J. Egan

  DOI：10.1016/j.ejmech.2011.02.026

  日期：2011.5

  A series of 12 new dibemethin (N-benzyl-N-methyl-1-phenylmethanamine) derivatives bearing an Naminomethyl group attached to the one phenyl ring and an H, CI, OCH3 or N(CH3)(2) group on the other have been synthesized. These compounds all showed strong chloroquine chemosensitizing activity, comparable to verapamil, when present at 1 mu M in an in vitro culture of the chloroquine-resistant W2 strain of the human malaria parasite, Plasmodium falciparum. Their N-formylated derivatives also exhibited resistance-reversing activity, but only at substantially higher IC10 concentrations. A number of the dibemethin derivatives were shown to inhibit chloroquine transport via the parasite's 'chloroquine resistance transporter' (PfCRT) in a Xenopus laevis oocyte expression system. The reduced resistance-reversing activity of the formylated compounds relative to their free amine counterparts can probably be ascribed to two factors: decreased accumulation of the formylated dibemethins within the parasite's internal digestive vacuole (believed to be the site of action of chloroquine), and a reduced ability to inhibit PfCRT. The resistance-reversing activity of the compounds described here demonstrates that the amino group need not be attached to the two aromatic rings via a three or four carbon chain as has been suggested by previous QSAR studies. These compounds may be useful as potential side chains for attaching to a 4,7-dichloroquinoline group in order to generate new resistance-reversing chloroquine analogues with inherent antimalarial activity. (C) 2011 Elsevier Masson SAS. All rights reserved.