2-(N-methyl-N-phenylamino)-3-chloronaphthalene-1,4-dione | 14422-76-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-(N-methyl-N-phenylamino)-3-chloronaphthalene-1,4-dione
• 英文别名: 2-chloro-3-(N-methylanilino)-1,4-naphthoquinone；2-Chlor-2--<1,4>naphthochinon；2-Chlor-3-(methylaminilino)-1.4-naphthochinon；2-Chlor-2-(N-methyl-anilino)-[1,4]naphthochinon；1,4-Naphthalenedione, 2-chloro-3-(methylphenylamino)-；2-chloro-3-(N-methylanilino)naphthalene-1,4-dione
• CAS: 14422-76-5
• 化学式: C₁₇H₁₂ClNO₂
• 分子量: 297.741
• InChiKey: LBICNJDBFBDRHW-UHFFFAOYSA-N

物化性质

• 熔点：
  102.5 °C
• 沸点：
  400.2±45.0 °C(Predicted)
• 密度：
  1.36±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  37.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(N-methyl-N-phenylamino)-3-chloronaphthalene-1,4-dione 、 1-氨基戊烷 在 1,1'-双(二苯基膦)二茂铁 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride sodium t-butanolate 作用下， 以 甲苯 为溶剂， 反应 6.0h， 以62%的产率得到2-(N-methylanilino)-3-(pentylamino)-1,4-naphthoquinone
  参考文献：
  名称：

  [1,1'-双(二苯基膦基)二茂铁]二氯钯/1,1'-双(二苯基膦基)二茂铁催化合成2,3-二氨基-1,4-萘醌

  摘要：

  描述了一种通过 2-氨基-3-氯-1,4-萘醌与胺的钯催化偶联合成 2,3-二氨基-1,4-萘醌衍生物的一般方法。使用[1,1'-双(二苯基膦基)二茂铁]二氯钯[PdCl 2 (dppf)]与1,1'-双(二苯基膦基)二茂铁(dppf)作为配体和钠的偶联过程的范围和限制对作为碱的叔丁醇进行了研究，发现它可以有效地催化 2-(芳基氨基)-3-氯-1,4-萘醌与伯芳基胺和烷基胺的偶联。应用该程序获得了一系列以前无法获得的新型2,3-二氨基-1,4-萘醌衍生物。

  DOI：

  10.1055/s-2007-965983
• 作为产物：
  描述：

  2,3-二氯-1,4-萘醌 、 N-甲基苯胺 以 乙醇 为溶剂， 以56%的产率得到2-(N-methyl-N-phenylamino)-3-chloronaphthalene-1,4-dione
  参考文献：
  名称：

  Synthesis, anticancer activity and QSAR study of 1,4-naphthoquinone derivatives

  摘要：

  A series of 2-substituted amino-3-chloro-1,4-naphthoquinone derivatives (3-12) were synthesized as anticancer agents and tested against four cancer cell lines including HepG2, HuCCA-1, A549 and MOLT-3. The most potent cytotoxic activity against the HepG2, HuCCA-1 and A549 cell lines was found to be m-acetylphenylamino-1,4-naphthoquinone (8) affording IC50 values of 4.758, 2.364 and 12.279 μM, respectively. On the other hand, p-acetylphenylamino-1,4-naphthoquinone (9) exhibited the most potent cytotoxic activity against the MOLT-3 cell line with an IC50 of 2.118 μM. Quantitative structure-activity relationship (QSAR) investigations provided good predictive performance as observed from cross-validated R of 0.9177-0.9753 and RMSE of 0.0614-0.1881. The effects of substituents at the 2-amino position on the naphthoquinone core structure and its corresponding influence on the cytotoxic activity were investigated by virtually constructing additional 1,4-naphthoquinone compounds (13-36) for which cytotoxic activities were predicted using equations obtained from the previously constructed QSAR models. Interpretation of informative descriptors from QSAR models revealed pertinent knowledge on physicochemical properties governing the cytotoxic activities of tested cancer cell lines. It is anticipated that the QSAR models developed herein could provide guidelines for further development of novel and potent anticancer agents.

  DOI：

  10.1016/j.ejmech.2014.07.024

文献信息

• Biological evaluation of donor-acceptor aminonaphthoquinones as antitumor agents
  作者：Julio Benites、Jaime A. Valderrama、Karina Bettega、Rozangela Curi Pedrosa、Pedro Buc Calderon、Julien Verrax

  DOI：10.1016/j.ejmech.2010.10.006

  日期：2010.12

  Several members of the phenylamino-1,4-naphthoquinone series were prepared in order to investigate structure-activity relationships (SAR) and to explore the antitumor effects associated with this scaffold. The cytotoxic effects of the aminoquinones (EC50) against a panel of cancer cell lines (MCF7, DU145 and T24 cells) and healthy fibroblasts (BALB/3T3) were assessed in vitro using the MTT reduction assay 48 h after drug exposure. SAR analysis of the aminonaphthoquinone series showed that insertion of a chlorine atom in the acceptor quinone nucleus and/or insertion of a methyl group at the nitrogen atom of the donor phenylamino group induced significant changes in cytotoxic activity. Quinones 7 and 9, which exhibited the highest selective indexes (5.73 and 6.29, respectively), were further characterized using the following assays: Colony formation, caspase-3 activity, and ATP content. The results showed that aminoquinone 7 strongly influenced ATP levels and impaired the proliferative capacity of T24 cells without activating caspase-3. (C) 2010 Elsevier Masson SAS. All rights reserved.
• MIXALINA, T. V.;KRASHENININA, V. I.;FOKIN, E. N.;RUBASHKO, S. V., IZV. CO AN CCCP. CEP. XIM. N.,(1990) N, S. 115-120
  作者：MIXALINA, T. V.、KRASHENININA, V. I.、FOKIN, E. N.、RUBASHKO, S. V.

  DOI：——

  日期：——
• AFANASEVA, G. B.;VYSOKOV, V. I.;CHUPAXIN, O. N.;UFIMTSEVA, I. S., XIMIYA GETEROTSIKL. SOEDIN., 1985, N 1, 49-52
  作者：AFANASEVA, G. B.、VYSOKOV, V. I.、CHUPAXIN, O. N.、UFIMTSEVA, I. S.

  DOI：——

  日期：——
• [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium/1,1′-Bis(diphenylphosphino)ferrocene Catalyzed Synthesis of 2,3-Diamino-1,4-naphthoquinones
  作者：John Reiner、Jun Chang、Xiao Wang、Xiu Zheng、Lei Wang、Wei Xie

  DOI：10.1055/s-2007-965983

  日期：2007.4

  coupling of 2-amino-3-chloro-1,4-naphthoquinones with amines is described. The scope and limitations of the coupling process using [1,1 '-bis(diphenylphosphino)ferrocene] dichloropalladium [PdCl 2 (dppf)], combined with 1,1'-bis(diphenylphosphino)ferrocene (dppf) as a ligand and sodium tert-butoxide as base were investigated, and found to catalyze efficiently the coupling of 2-(arylamino)-3-chloro- 1,4-naphthoquinones

  描述了一种通过 2-氨基-3-氯-1,4-萘醌与胺的钯催化偶联合成 2,3-二氨基-1,4-萘醌衍生物的一般方法。使用[1,1'-双(二苯基膦基)二茂铁]二氯钯[PdCl 2 (dppf)]与1,1'-双(二苯基膦基)二茂铁(dppf)作为配体和钠的偶联过程的范围和限制对作为碱的叔丁醇进行了研究，发现它可以有效地催化 2-(芳基氨基)-3-氯-1,4-萘醌与伯芳基胺和烷基胺的偶联。应用该程序获得了一系列以前无法获得的新型2,3-二氨基-1,4-萘醌衍生物。
• Synthesis, anticancer activity and QSAR study of 1,4-naphthoquinone derivatives
  作者：Veda Prachayasittikul、Ratchanok Pingaew、Apilak Worachartcheewan、Chanin Nantasenamat、Supaluk Prachayasittikul、Somsak Ruchirawat、Virapong Prachayasittikul

  DOI：10.1016/j.ejmech.2014.07.024

  日期：2014.9

  A series of 2-substituted amino-3-chloro-1,4-naphthoquinone derivatives (3-12) were synthesized as anticancer agents and tested against four cancer cell lines including HepG2, HuCCA-1, A549 and MOLT-3. The most potent cytotoxic activity against the HepG2, HuCCA-1 and A549 cell lines was found to be m-acetylphenylamino-1,4-naphthoquinone (8) affording IC50 values of 4.758, 2.364 and 12.279 μM, respectively. On the other hand, p-acetylphenylamino-1,4-naphthoquinone (9) exhibited the most potent cytotoxic activity against the MOLT-3 cell line with an IC50 of 2.118 μM. Quantitative structure-activity relationship (QSAR) investigations provided good predictive performance as observed from cross-validated R of 0.9177-0.9753 and RMSE of 0.0614-0.1881. The effects of substituents at the 2-amino position on the naphthoquinone core structure and its corresponding influence on the cytotoxic activity were investigated by virtually constructing additional 1,4-naphthoquinone compounds (13-36) for which cytotoxic activities were predicted using equations obtained from the previously constructed QSAR models. Interpretation of informative descriptors from QSAR models revealed pertinent knowledge on physicochemical properties governing the cytotoxic activities of tested cancer cell lines. It is anticipated that the QSAR models developed herein could provide guidelines for further development of novel and potent anticancer agents.