4-Bromo-5,5-dimethyl-6-oxa-15,22-diazapentacyclo[12.8.0.02,7.08,13.016,21]docosa-1(22),2(7),8,10,12,14,16,18,20-nonaene | 74693-30-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 4-Bromo-5,5-dimethyl-6-oxa-15,22-diazapentacyclo[12.8.0.02,7.08,13.016,21]docosa-1(22),2(7),8,10,12,14,16,18,20-nonaene
• CAS: 74693-30-4
• 化学式: C₂₁H₁₇BrN₂O
• 分子量: 393.283
• InChiKey: BVHHUVPYPHZAII-UHFFFAOYSA-N

物化性质

• 熔点：
  189 °C (decomp)
• 沸点：
  570.4±40.0 °C(predicted)
• 密度：
  1.462±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  25
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  35
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-Bromo-5,5-dimethyl-6-oxa-15,22-diazapentacyclo[12.8.0.02,7.08,13.016,21]docosa-1(22),2(7),8,10,12,14,16,18,20-nonaene 在 双氧水 、 乙酸酐 作用下， 以 氯仿 、 水 为溶剂， 反应 24.0h， 以33%的产率得到11-Bromo-10,10-dimethyl-22-oxido-9-oxa-15-aza-22-azoniatetracyclo[12.8.0.02,7.016,21]docosa-1(22),2,4,6,14,16,18,20-octaene-8,13-dione
  参考文献：
  名称：

  A macrolactone from benzo[a]phenazine with potent activity against Mycobacterium tuberculosis

  摘要：

  We report here an alternative to the MCPBA or ozonolysis-based oxidation methods of quinoxaline-featuring compounds prepared from beta-lapachones. The use of peracetic acid allowed a simple preparation of the corresponding macrolactones by cleavage of the ring system. These lactones were evaluated for their antimycobacterial potential and compound 4 turned out to have an MIC of 0.62 mu g per mL on Mycocabteriumtuberculosis H37Rv. These results justify further research into its value as a potential lead for an original treatment of tuberculosis. (C) 2008 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2008.06.014
• 作为产物：
  描述：

  3'-bromo-β-lapachone 、 邻苯二胺 在 溶剂黄146 作用下， 生成 4-Bromo-5,5-dimethyl-6-oxa-15,22-diazapentacyclo[12.8.0.02,7.08,13.016,21]docosa-1(22),2(7),8,10,12,14,16,18,20-nonaene
  参考文献：
  名称：

  A macrolactone from benzo[a]phenazine with potent activity against Mycobacterium tuberculosis

  摘要：

  We report here an alternative to the MCPBA or ozonolysis-based oxidation methods of quinoxaline-featuring compounds prepared from beta-lapachones. The use of peracetic acid allowed a simple preparation of the corresponding macrolactones by cleavage of the ring system. These lactones were evaluated for their antimycobacterial potential and compound 4 turned out to have an MIC of 0.62 mu g per mL on Mycocabteriumtuberculosis H37Rv. These results justify further research into its value as a potential lead for an original treatment of tuberculosis. (C) 2008 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2008.06.014

文献信息

• Gupta, R. B.; Khanna, R. N., Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1980, vol. 19, # 1, p. 17 - 19
  作者：Gupta, R. B.、Khanna, R. N.

  DOI：——

  日期：——
• Antimalarial activity of phenazines from lapachol, β-lapachone and its derivatives against Plasmodium falciparum in vitro and Plasmodium berghei in vivo
  作者：Valter F de Andrade-Neto、Marı́lia O.F Goulart、Jorge F da Silva Filho、Matuzalém J da Silva、Maria do Carmo F.R Pinto、Antônio V Pinto、Mariano G Zalis、Luzia H Carvalho、Antoniana U Krettli

  DOI：10.1016/j.bmcl.2003.12.069

  日期：2004.3

  The antimalarial activity of benzo[a]phenazines synthesized from 1,2-naphthoquinone, lapachol, beta-lapachone and several derivatives have been tested against Plasmodium falciparum in vitro using isolates of parasites with various susceptibilities to chloroquine and/or mefloquine. Parasite growth in the presence of the test drugs was measured by incorporation of [H-3]-hipox-anthine in comparison to controls with no drugs, always testing in parallel chloroquine, a standard antimalarial. Among seven benzophenazines tested, four had significant in vitro activities; important, the parasites resistant to chloroquine were more susceptible to the active phenazines in vitro. The doses of phenazines causing 50% inhibition of parasite growth varied from 1.67 to 9.44 muM. The two most active ones were also tested in vivo against Plasmodium berghei in mice, in parallel with lapachol and beta-lapachone. The 3-sulfonic acid-beta-lapachone-derived phenazine was the most active causing up to 98% inhibition of parasitaemia in long term treatment (7 doses) subcutaneouly, whereas the phenazine from 3-bromo-beta-lapachone was inactive. Thus, these simple phenazines, containing polar (-Br,-I) and ionizable (-SO3H, -OH) groups, easily synthesized from cheap, natural or synthetic precursors (lapachol and beta-lapachone), at rather low cost, provide prototypes for development of new antimalarials aiming the chloroquine resistant parasites. (C) 2004 Elsevier Ltd. All rights reserved.
• A macrolactone from benzo[a]phenazine with potent activity against Mycobacterium tuberculosis
  作者：Raphael S.F. Silva、Maria do Carmo F.R. Pinto、Marília O.F. Goulart、José D. de Souza Filho、Ivan Neves Jr.、Maria Cristina S. Lourenço、Antonio V. Pinto

  DOI：10.1016/j.ejmech.2008.06.014

  日期：2009.5

  We report here an alternative to the MCPBA or ozonolysis-based oxidation methods of quinoxaline-featuring compounds prepared from beta-lapachones. The use of peracetic acid allowed a simple preparation of the corresponding macrolactones by cleavage of the ring system. These lactones were evaluated for their antimycobacterial potential and compound 4 turned out to have an MIC of 0.62 mu g per mL on Mycocabteriumtuberculosis H37Rv. These results justify further research into its value as a potential lead for an original treatment of tuberculosis. (C) 2008 Elsevier Masson SAS. All rights reserved.