1-(azidomethyl)-2-(bromomethyl)benzene | 887144-05-0

• 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)-2-(bromomethyl)benzene
• CAS: 887144-05-0
• 化学式: C₈H₈BrN₃
• 分子量: 226.076
• InChiKey: MZDRHFTZCKXYNF-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)-2-(bromomethyl)benzene 在 sodium azide 作用下， 以 乙醇 为溶剂， 反应 1.5h， 以93%的产率得到1,2-双(叠氮甲基)苯
  参考文献：
  名称：

  Dipolar HCP materials as alternatives to DMF solvent for azide-based synthesis

  摘要：

  含有丰富且灵活的DMF基团的超交联聚合物HCP-DMF和HCP-DMF-SO₃H被设计并合成。

  DOI：

  10.1039/d1gc02002a
• 作为产物：
  描述：

  1,2-二(溴甲基)苯 在 sodium azide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 1-(azidomethyl)-2-(bromomethyl)benzene
  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

文献信息

• Structure-activity-relationship study of semi-synthetically modified fusicoccins on their stabilization effect for 14-3-3-phospholigand interactions
  作者：Nanami Ogino、Ryoma Masuda、Louvy Lynn Punzalan、Emi Yamashita、Shota Igaue、Yoshihisa Inoue、Junko Ohkanda

  DOI：10.1016/j.bmc.2022.117020

  日期：2022.11

  plasma membrane H+-ATPase by forming a stable ternary complex. Previous studies demonstrated that structurally modified FC-A derivatives exhibit significant antitumor activities but their synthesis involves an explosive reagent, limiting their utility and opportunities for further structure–activity-relationship studies. In this study, we synthesized a series of FC derivatives by introducing various substituents

  二萜葡糖苷 fusicoccin-A (FC-A) 是一种真菌植物毒素，可稳定植物 14-3-3 蛋白与质膜 H +的相互作用-ATPase 通过形成稳定的三元复合物。先前的研究表明，结构修饰的 FC-A 衍生物表现出显着的抗肿瘤活性，但它们的合成涉及爆炸性试剂，限制了它们的效用和进一步结构-活性关系研究的机会。在本研究中，我们通过在 fusicoccan 支架和糖苷部分上引入各种取代基合成了一系列 FC 衍生物，并评估了它们对 14-3-3 与荧光标记的 mode-1 和 mode-3 磷酸肽结合的稳定作用。 . 结果表明，在糖苷部分的 6'-位引入氨基可提高稳定性。此外，基于细胞的评估表明 6'-氨基苄基21b表现出比以前开发的 FC 剂更高的抗增殖活性。
• 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.
• A Structurally Diverse Library of Polycyclic Lactams Resulting from Systematic Placement of Proximal Functional Groups
  作者：Judith M. Mitchell、Jared T. Shaw

  DOI：10.1002/anie.200503341

  日期：2006.3.6
• 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.
• Dipolar HCP materials as alternatives to DMF solvent for azide-based synthesis
  作者：Feng Gao、Rongxian Bai、Minghao Li、Yanlong Gu

  DOI：10.1039/d1gc02002a

  日期：——

  Hypercrosslinked polymers HCP-DMF and HCP-DMF-SO₃H containing abundant and flexible DMF moieties were designed and synthesized.

  含有丰富且灵活的DMF基团的超交联聚合物HCP-DMF和HCP-DMF-SO₃H被设计并合成。