N,N-diethyl-5-pyridin-3-yliminobenzo[a]phenoxazin-9-amine | 1187533-47-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: N,N-diethyl-5-pyridin-3-yliminobenzo[a]phenoxazin-9-amine
• CAS: 1187533-47-6
• 化学式: C₂₅H₂₂N₄O
• 分子量: 394.476
• InChiKey: IBJCPIPDXSTCNE-UHFFFAOYSA-N

物化性质

• 熔点：
  198-199 °C
• 沸点：
  551.9±50.0 °C(predicted)
• 密度：
  1.22±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  50.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N,N-diethyl-5-pyridin-3-yliminobenzo[a]phenoxazin-9-amine 、 六乙二醇单对甲苯磺酸酯 以 乙腈 为溶剂， 反应 48.0h， 以33%的产率得到3-((9-(diethylamino)-5H-benzo[a]phenoxazin-5-ylidene)amino)-1-(2,5,8,11,14,17-hexaoxanonadecan-19-yl)pyridin-1-ium chloride
  参考文献：
  名称：

  The improvement of lysosome targetability with oligoethyleneoxy chains linked benzo[a]phenoxazine

  摘要：

  In order to improve lysosome targetability of probes, fluorescent probes based on benzo[a]phenoxazine attaching different length oligoethyleneoxy chains were designed and prepared. Probes 2a-c containing N-pyridineium-3-yl exhibited almost ON-OFF near-infrared emission responses at 697-701 nm from pH 2.8 to 7.2, and the calculated pK(a) values of 2a-c were 4.90, 4.92 and 5.03 respectively. More importantly, fluorescent imaging experiments indicated that probes 2a-c were all lysosome biomarkers for Ges-1 and HeLa cells, which was because the introduction of oligoethyleneoxy groups improved the biocompatibility of probes, so that the probes 2a-c were better transported to lysosomes via the endocytosis pathway of the cells. Moreover, the probe 2a was selected as a representative, which not only showed good reversibility and selectivity, but used to successfully image lysosomal pH increases induced by chloroquine.

  DOI：

  10.1016/j.bmcl.2018.07.004
• 作为产物：
  描述：

  3-氨基吡啶 、 9-(diethylamino)benzo[a]phenoxazin-7-ium nitrate 在 air 作用下， 以 乙醇 为溶剂， 反应 24.0h， 生成 N,N-diethyl-5-pyridin-3-yliminobenzo[a]phenoxazin-9-amine
  参考文献：
  名称：

  Discovery of Novel Benzo[a]phenoxazine SSJ-183 as a Drug Candidate for Malaria

  摘要：

  Malaria is a serious infectious disease caused by protozoan parasites in tropical and subtropical regions. Even inhabitants of temperate zones are exposed to the danger of malaria infection because of travel and global warming. Novel, effective,safe, and inexpensive drugs are required to treat malaria and. . contribute to the global goal of eradication. A search for new antimalarial-agents has by the synthesis of by biological evaluations. The derivative SSJ-183(5) having a 4-aminopyridine group, showed an IC50 value against Plasmodium falciparum of 7.6 nM and a selectivity index of > 7300: Cure was acheived by three oral doses of 5 at 100 mg/kg to mice infected with the Plasmodium berghei ANKA strain. The safety of 5 was supported acute toxicity testing in mice with single doses up to 2000 mg/kg po, chromosome aberration test, in vitro as well as in vivo micronucleus tests and phototoxicity studies in mice. Thus, 5 is a promising candidate as a new antimalarial agent.

  DOI：

  10.1021/ml100120a

文献信息

• Reversible Near-Infrared pH Probes Based on Benzo[<i>a</i>]phenoxazine
  作者：Wu Liu、Ru Sun、Jian-Feng Ge、Yu-Jie Xu、Ying Xu、Jian-Mei Lu、Isaum Itoh、Masataka Ihara

  DOI：10.1021/ac4013539

  日期：2013.8.6

  Several benzo[a]phenoxazine derivatives containing substituted N-aromatic groups are evaluated for their pH-dependent absorption and emission properties. Among the compounds exhibiting optical responses under near-neutral and subacid pH conditions, benzo[a]phenoxazine derivatives with an electron-withdrawing aromatic group attached to nitrogen of the imino group show potential application as near-infrared

  评价了几种含有取代的N-芳族基团的苯并[ a ]吩恶嗪衍生物的pH依赖性吸收和发射性质。在近中性和亚酸性pH条件下表现出光学响应的​​化合物中，亚氨基基团的氮上带有吸电子芳族基团的苯并[ a ]吩恶嗪衍生物显示出作为近红外pH传感器的潜在应用。设计并合成了三种基于具有不同吡啶鎓结构的苯并[ a ]吩恶嗪的水溶性pH探针。在含0.1％二甲基亚砜（DMSO）的缓冲溶液中，它们的pH依赖可逆发射，位于625–850 nm，荧光增强8.2–40.1倍，其计算出的p Ka值分别为2.7、5.8和7.1。包含三种苯并[ a ]吩恶嗪的复合探针在pH 1.9-8.0范围内显示线性的pH-发射关系。还报道了使用HeLa细胞的体外测定法实时检测细胞内pH的方法。
• Discovery of Novel Benzo[<i>a</i>]phenoxazine SSJ-183 as a Drug Candidate for Malaria
  作者：Jian-Feng Ge、Chika Arai、Mei Yang、Abu Bakar Md.、Jun Lu、Nasser S. M. Ismail、Sergio Wittlin、Marcel Kaiser、Reto Brun、Susan A. Charman、Tien Nguyen、Julia Morizzi、Isamu Itoh、Masataka Ihara

  DOI：10.1021/ml100120a

  日期：2010.10.14

  Malaria is a serious infectious disease caused by protozoan parasites in tropical and subtropical regions. Even inhabitants of temperate zones are exposed to the danger of malaria infection because of travel and global warming. Novel, effective,safe, and inexpensive drugs are required to treat malaria and. . contribute to the global goal of eradication. A search for new antimalarial-agents has by the synthesis of by biological evaluations. The derivative SSJ-183(5) having a 4-aminopyridine group, showed an IC50 value against Plasmodium falciparum of 7.6 nM and a selectivity index of > 7300: Cure was acheived by three oral doses of 5 at 100 mg/kg to mice infected with the Plasmodium berghei ANKA strain. The safety of 5 was supported acute toxicity testing in mice with single doses up to 2000 mg/kg po, chromosome aberration test, in vitro as well as in vivo micronucleus tests and phototoxicity studies in mice. Thus, 5 is a promising candidate as a new antimalarial agent.
• The improvement of lysosome targetability with oligoethyleneoxy chains linked benzo[a]phenoxazine
  作者：Wei-Jin Zhu、Jin-Yun Niu、Ru Sun、Yu-Jie Xu、Jian-Feng Ge

  DOI：10.1016/j.bmcl.2018.07.004

  日期：2018.9

  In order to improve lysosome targetability of probes, fluorescent probes based on benzo[a]phenoxazine attaching different length oligoethyleneoxy chains were designed and prepared. Probes 2a-c containing N-pyridineium-3-yl exhibited almost ON-OFF near-infrared emission responses at 697-701 nm from pH 2.8 to 7.2, and the calculated pK(a) values of 2a-c were 4.90, 4.92 and 5.03 respectively. More importantly, fluorescent imaging experiments indicated that probes 2a-c were all lysosome biomarkers for Ges-1 and HeLa cells, which was because the introduction of oligoethyleneoxy groups improved the biocompatibility of probes, so that the probes 2a-c were better transported to lysosomes via the endocytosis pathway of the cells. Moreover, the probe 2a was selected as a representative, which not only showed good reversibility and selectivity, but used to successfully image lysosomal pH increases induced by chloroquine.