4-(二丁基氨基)-3,5-二硝基-N-苯基苯磺酰胺 | 619267-15-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-(二丁基氨基)-3,5-二硝基-N-苯基苯磺酰胺
• 英文名称: N1-phenyl-3,5-dinitro-N4,N4-di-n-butylsulfanilamide
• 英文别名: GB-II-150；4-(dibutylamino)-3,5-dinitro-N-phenylbenzenesulfonamide
• CAS: 619267-15-1
• 化学式: C₂₀H₂₆N₄O₆S
• 分子量: 450.516
• InChiKey: FYMAZDOJZUMVIY-UHFFFAOYSA-N

物化性质

• 熔点：
  156 °C(Solv: dichloromethane (75-09-2); hexane (110-54-3))
• 沸点：
  586.0±60.0 °C(Predicted)
• 密度：
  1.327±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  31
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  149
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-(二丁基氨基)-3,5-二硝基-N-苯基苯磺酰胺 在 palladium on activated charcoal 氢气 作用下， 以 乙酸乙酯 为溶剂， 反应 24.0h， 以98%的产率得到3,5-diamino-4-(dibutylamino)-N-phenylbenzenesulfonamide
  参考文献：
  名称：

  Synthesis, biological evaluation, and molecular modeling of 3,5-substituted-N1-phenyl-N4,N4-di-n-butylsulfanilamides as antikinetoplastid antimicrotubule agents

  摘要：

  Dinitroanilines are of interest as antiprotozoal lead compounds because of their selective activity against the tubulin of these organisms, but concern has been raised due to the potentially mutagenic nitro groups. Analogues of N-1 -phenyl-3,5-dinitro-N-4,N-4-di-n-butylsulfanilamide (GB-II-150, compound 2b), a selective antimitotic agent against African trypanosomes and Leishmania. have been prepared where the nitro groups are replaced with amino, chloro, cyano, carboxylate, methyl ester, amide, and methyl ketone moieties. Dicyano compound 5 displays IC50 values that are comparable to 2b against purified leishmanial tubulin assembly (6.6 vs 7.4 mu M) Trvpanosoma brucei brucei growth in vitro (0.26 vs 0.18 mu M), Leishmania donovani axenic amastigote growth in vitro (4.4 vs 2.3 mu M), and in vitro toxicity against Vero cells (16 vs 9.7 mu M). Computational studies provide a rationale or the antiparasitic order of activity of these analogues and further insight into the role of the substituents at the 3 and 5 positions of the sulfanilamide ring. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.06.042
• 作为产物：
  描述：

  potassium 4-chloro-3,5-dinitrobenzenesulfonate 在 吡啶 、 五氯化磷 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 8.0h， 生成 4-(二丁基氨基)-3,5-二硝基-N-苯基苯磺酰胺
  参考文献：
  名称：

  Synthesis and Antitubulin Activity of N- and N⁴-Substituted 3,5-Dinitro Sulfanilamides against African Trypanosomes and Leishmania

  摘要：

  Thirty analogues of N-1-phenyl-3,5-dinitro-N-4,N-4-di-n-propylsulfanilamide (GB-II-5, compound 3), a new antikinetoplastid antimitotic agent, have been synthesized and evaluated. The addition of simple functional groups to the N1 aromatic ring generally decreases antiparasitic and antimitotic potency, but placement of a dibutyl substituent at the N4 nitrogen to give N-1-phenyl-3,5-dinitro-N-4,N-4-di-n-butylsulfanilamide (compound 35) augments antitrypanosomal and antileishmanial activity. Compound 35 possesses IC50 values of 0.12 and 2.6 muM against cultured T. brucei and L. donovani amastigote-like forms, surpassing the activity of compound 3 against these parasites by 3.4- and 1.9-fold, respectively. Compound 35 inhibits the assembly of leishmanial tubulin with an IC50 of 6.9 muM and displays antimitotic effects in cultured T brucei as assessed by flow cytometry, but shows little effect on purified mammalian tubulin, and displays 100-fold selectivity for trypanosomes over two mammalian cell lines. Although 3 and 35 were not effective in initial in vivo antitrypanosomal assays, the in vitro potency and ;selectivity of these compounds make N-1-aryl-3,5-dinitro-N-4,N-4-dialkylsulfanilamides a promising new class of antikinetoplastid agents that act on parasite tubulin.

  DOI：

  10.1021/jm0304461

文献信息

• Synthesis and Antitubulin Activity of N- and N⁴-Substituted 3,5-Dinitro Sulfanilamides against African Trypanosomes and <i>Leishmania</i>
  作者：Gautam Bhattacharya、Johnathan Herman、Dawn Delfín、Manar M. Salem、Todd Barszcz、Mike Mollet、Guy Riccio、Reto Brun、Karl A. Werbovetz

  DOI：10.1021/jm0304461

  日期：2004.3.1

  Thirty analogues of N-1-phenyl-3,5-dinitro-N-4,N-4-di-n-propylsulfanilamide (GB-II-5, compound 3), a new antikinetoplastid antimitotic agent, have been synthesized and evaluated. The addition of simple functional groups to the N1 aromatic ring generally decreases antiparasitic and antimitotic potency, but placement of a dibutyl substituent at the N4 nitrogen to give N-1-phenyl-3,5-dinitro-N-4,N-4-di-n-butylsulfanilamide (compound 35) augments antitrypanosomal and antileishmanial activity. Compound 35 possesses IC50 values of 0.12 and 2.6 muM against cultured T. brucei and L. donovani amastigote-like forms, surpassing the activity of compound 3 against these parasites by 3.4- and 1.9-fold, respectively. Compound 35 inhibits the assembly of leishmanial tubulin with an IC50 of 6.9 muM and displays antimitotic effects in cultured T brucei as assessed by flow cytometry, but shows little effect on purified mammalian tubulin, and displays 100-fold selectivity for trypanosomes over two mammalian cell lines. Although 3 and 35 were not effective in initial in vivo antitrypanosomal assays, the in vitro potency and ;selectivity of these compounds make N-1-aryl-3,5-dinitro-N-4,N-4-dialkylsulfanilamides a promising new class of antikinetoplastid agents that act on parasite tubulin.
• Synthesis, biological evaluation, and molecular modeling of 3,5-substituted-N1-phenyl-N4,N4-di-n-butylsulfanilamides as antikinetoplastid antimicrotubule agents
  作者：Tesmol G. George、Molla M. Endeshaw、Rachel E. Morgan、Kiran V. Mahasenan、Dawn A. Delfín、Mitali S. Mukherjee、Adam J. Yakovich、Jean Fotie、Chenglong Li、Karl A. Werbovetz

  DOI：10.1016/j.bmc.2007.06.042

  日期：2007.9

  Dinitroanilines are of interest as antiprotozoal lead compounds because of their selective activity against the tubulin of these organisms, but concern has been raised due to the potentially mutagenic nitro groups. Analogues of N-1 -phenyl-3,5-dinitro-N-4,N-4-di-n-butylsulfanilamide (GB-II-150, compound 2b), a selective antimitotic agent against African trypanosomes and Leishmania. have been prepared where the nitro groups are replaced with amino, chloro, cyano, carboxylate, methyl ester, amide, and methyl ketone moieties. Dicyano compound 5 displays IC50 values that are comparable to 2b against purified leishmanial tubulin assembly (6.6 vs 7.4 mu M) Trvpanosoma brucei brucei growth in vitro (0.26 vs 0.18 mu M), Leishmania donovani axenic amastigote growth in vitro (4.4 vs 2.3 mu M), and in vitro toxicity against Vero cells (16 vs 9.7 mu M). Computational studies provide a rationale or the antiparasitic order of activity of these analogues and further insight into the role of the substituents at the 3 and 5 positions of the sulfanilamide ring. (c) 2007 Elsevier Ltd. All rights reserved.