3,5-二硝基-N4,N4-二正丙基磺酰氯 | 37851-36-8

• 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: 3,5-二硝基-N4,N4-二正丙基磺酰氯
• 英文名称: 3,5-dinitro-N⁴,N⁴-di-n-propylsulfonyl chloride
• 英文别名: 4-(dipropylamino)-3,5-dinitrobenzenesulfonyl chloride；Szy9J5KL4V
• CAS: 37851-36-8
• 化学式: C₁₂H₁₆ClN₃O₆S
• 分子量: 365.795
• InChiKey: FUTUZDJZCFHSKB-UHFFFAOYSA-N

物化性质

• 沸点：
  474.1±45.0 °C(Predicted)
• 密度：
  1.441±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  137
• 氢给体数：
  0
• 氢受体数：
  7

安全信息

• 海关编码：
  2921499090

反应信息

• 作为反应物：
  描述：

  3,5-二硝基-N4,N4-二正丙基磺酰氯 在 氨 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以286 mg的产率得到氨磺乐灵
  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
• 作为产物：
  描述：

  potassium 4-chloro-3,5-dinitrobenzenesulfonate 在 五氯化磷 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 生成 3,5-二硝基-N4,N4-二正丙基磺酰氯
  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

• Selective Late‐Stage Sulfonyl Chloride Formation from Sulfonamides Enabled by Pyry‐BF ₄
  作者：Alejandro Gómez‐Palomino、Josep Cornella

  DOI：10.1002/anie.201910895

  日期：2019.12.9

  Reported here is a simple and practical functionalization of primary sulfonamides, by means of a pyrylium salt (Pyry-BF4 ), with nucleophiles. This simple reagent activates the poorly nucleophilic NH2 group in a sulfonamide, enabling the formation of one of the best electrophiles in organic synthesis: a sulfonyl chloride. Because of the variety of primary sulfonamides in pharmaceutical contexts, special

  此处报道的是通过吡喃鎓盐（Pyry-BF4）与亲核试剂一起对伯磺酰胺进行简单实用的官能化。这种简单的试剂可以活化磺酰胺中不良的亲核NH 2基团，从而可以形成有机合成中最好的亲电试剂之一：磺酰氯。由于在药物环境中伯磺酰胺的多样性，因此特别注意集中在通过后期形成相应的磺酰氯而直接转化为稠密官能化的伯磺酰胺。多种亲核试剂可参与该转化，因此允许合成复杂的磺酰胺，磺酸盐，硫化物，磺酰氟和磺酸。
• Antileishmanial dinitroaniline sulfonamides with activity against parasite tubulin
  作者：Gautam Bhattacharya、Manar M Salem、Karl A Werbovetz

  DOI：10.1016/s0960-894x(02)00465-1

  日期：2002.9

  Novel dinitroaniline sulfonamides based on the herbicide oryzalin 3 were synthesized and evaluated for activity against the parasitic protozoan Leishmania donovani and against leishmanial tubulin, the putative antiparasitic target of oryzalin. A subset of these compounds possess more activity against both Leishmania and the target protein in vitro. Compound 20 displays improved potency against leishmanial tubulin and is 13.4-fold more active against L. donovani axenic amastigotes than oryzalin. (C) 2002 Elsevier Science Ltd. All rights reserved.
• 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.
• Antikinetoplastid antimitotic activity and metabolic stability of dinitroaniline sulfonamides and benzamides
  作者：Tesmol G. George、Jayaseharan Johnsamuel、Dawn A. Delfín、Adam Yakovich、Mitali Mukherjee、Mitch A. Phelps、James T. Dalton、Dan L. Sackett、Marcel Kaiser、Reto Brun、Karl A. Werbovetz

  DOI：10.1016/j.bmc.2006.04.017

  日期：2006.8

  N-1-Phenyl-3,5-dinitro-N-4,N-4-di-n-propylsulfanilamide (1) and N-1-phenyl-3,5-dinitro-N-4,N-4-di-n-butylsulfanilamide (2) show potent in vitro antimitotic activity against kinetoplastid parasites but display poor in vivo activity. Seventeen new dinitroaniline sulfonamide and eleven new benzamide analogs of these leads are reported here. Nine of the sulfonamides display in vitro IC50 values under 500 nM against African trypanosomes, and the most active antikinetoplastid compounds also inhibit the in vitro assembly of purified leishmanial tubulin with potencies similar to that of 2. While several of the potent compounds are rapidly degraded by rat liver S9 fractions in vitro, N-1-(3-hydroxy)phenyl-3,5-dinitro-N-4,N-4-di-n-butylsulfanilamide (21) displays an IC50 value of 260 nM against African trypanosomes in vitro and is more stable than 2 in the in vitro metabolism assay. (c) 2006 Elsevier Ltd. All rights reserved.
• Synthesis and evaluation of oryzalin analogs against Toxoplasma gondii
  作者：Molla M. Endeshaw、Catherine Li、Jessica de Leon、Ni Yao、Kirk Latibeaudiere、Kokku Premalatha、Naomi Morrissette、Karl A. Werbovetz

  DOI：10.1016/j.bmcl.2010.07.003

  日期：2010.9

  The synthesis and evaluation of 20 dinitroanilines and related compounds against the obligate intracellular parasite Toxoplasma gondii is reported. Using in vitro cultures of parasites in human fibroblasts, we determined that most of these compounds selectively disrupted Toxoplasma microtubules, and several displayed sub-micromolar potency against the parasite. The most potent compound was N(1),N(1)-dipropyl-2,6-dinitro-4-(trifluoromethyl)-1,3-benzenediamine (18b), which displayed an IC(50) value of 36 nM against intracellular T. gondii. Based on these data and another recent report [Ma, C.; Tran, J.; Gu, F.; Ochoa, R.; Li, C.; Sept, D.; Werbovetz, K.; Morrissette, N. Antimicrob. Agents Chemother. 2010, 54, 1453], an antimitotic structure-activity relationship for dinitroanilines versus Toxoplasma is presented. (C) 2010 Elsevier Ltd. All rights reserved.