N-hexyl-N-methyl-4-nitroaniline | 138200-74-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-hexyl-N-methyl-4-nitroaniline
• CAS: 138200-74-5
• 化学式: C₁₃H₂₀N₂O₂
• 分子量: 236.314
• InChiKey: SGTAGQDNMIIMLJ-UHFFFAOYSA-N

物化性质

• 沸点：
  359.3±25.0 °C(Predicted)
• 密度：
  1.065±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  49.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-hexyl-N-methyl-4-nitroaniline 在 platinum on activated charcoal 盐酸 、 氢气 作用下， 以 甲醇 为溶剂， 反应 0.5h， 生成 9-{[4-(N-hexyl-N-methylamino)phenyl]amino}-6-chloro-2-methoxyacridine
  参考文献：
  名称：

  Structure−Activity Relationships for the Antileishmanial and Antitrypanosomal Activities of 1‘-Substituted 9-Anilinoacridines

  摘要：

  Members of the class of 9-anilinoacridine topoisomerase II inhibitors bearing lipophilic electron-donating 1'-anilino substituents are active against both the promastigote and amastigote forms of the parasite Leishmania major. A series of analogues of the known 1'-NHhexyl lead compound were prepared and evaluated against L. major in macrophage culture to further develop structure-activity relationships (SAR). Toxicity toward mammalian cells was measured in a human leukemia cell line, and the ratio of the two IC50 values (IC50(J)/IC50(L)) was used as a measure of the in vitro therapeutic index (IVTI). A 3,6-diNMe(2) substitution pattern on the acridine greatly increased toxicity to L. major without altering mammalian toxicity, increasing IVTIs over that of the lead compound. The 2-OMe, 6-Cl acridine substitution pattern used in the antimalarial drug mepacrine also resulted in potent antileishmanial activity and high IVTIs. Earlier suggestions of the utility of 2'-OR groups in lowering mammalian cytotoxicity were not borne out in this wider study. A series of very lipophilic 1'-NRR (symmetric dialkylamino)-substituted analogues showed relatively high antileishmanial potency, but no clear trend was apparent across the series, and none were superior to the 1'-NH(CH2)(5)Me subclass. Subsets of the most active 1'-N(R)(CH2)(5)Me- and 1'-N(alkyl)(2)-substituted compounds against L. major were also evaluated against Leishmania donovani, Trypanosoma cruzi, and Trypanosoma brucei, but no consistent SAR could be discerned in these physiologically diverse test systems. The present study has confirmed earlier conclusions that lipophilic electron-donating groups at the 1'-position of 9-anilinoacridines provide high activity against L. major, but the SAR patterns observed do not carry over to the other parasites studied.

  DOI：

  10.1021/jm970232h
• 作为产物：
  描述：

  N-methyl-4-N-(4-nitrophenyl)hexanamide 在 dimethyl sulfide borane 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以85%的产率得到N-hexyl-N-methyl-4-nitroaniline
  参考文献：
  名称：

  Structure−Activity Relationships for the Antileishmanial and Antitrypanosomal Activities of 1‘-Substituted 9-Anilinoacridines

  摘要：

  Members of the class of 9-anilinoacridine topoisomerase II inhibitors bearing lipophilic electron-donating 1'-anilino substituents are active against both the promastigote and amastigote forms of the parasite Leishmania major. A series of analogues of the known 1'-NHhexyl lead compound were prepared and evaluated against L. major in macrophage culture to further develop structure-activity relationships (SAR). Toxicity toward mammalian cells was measured in a human leukemia cell line, and the ratio of the two IC50 values (IC50(J)/IC50(L)) was used as a measure of the in vitro therapeutic index (IVTI). A 3,6-diNMe(2) substitution pattern on the acridine greatly increased toxicity to L. major without altering mammalian toxicity, increasing IVTIs over that of the lead compound. The 2-OMe, 6-Cl acridine substitution pattern used in the antimalarial drug mepacrine also resulted in potent antileishmanial activity and high IVTIs. Earlier suggestions of the utility of 2'-OR groups in lowering mammalian cytotoxicity were not borne out in this wider study. A series of very lipophilic 1'-NRR (symmetric dialkylamino)-substituted analogues showed relatively high antileishmanial potency, but no clear trend was apparent across the series, and none were superior to the 1'-NH(CH2)(5)Me subclass. Subsets of the most active 1'-N(R)(CH2)(5)Me- and 1'-N(alkyl)(2)-substituted compounds against L. major were also evaluated against Leishmania donovani, Trypanosoma cruzi, and Trypanosoma brucei, but no consistent SAR could be discerned in these physiologically diverse test systems. The present study has confirmed earlier conclusions that lipophilic electron-donating groups at the 1'-position of 9-anilinoacridines provide high activity against L. major, but the SAR patterns observed do not carry over to the other parasites studied.

  DOI：

  10.1021/jm970232h

文献信息

• N-Dealkylation-N-nitrosation of tertiary aromatic amines by N-butyl nitrite
  作者：Giancarlo Verardo、Angelo G. Giumanini、Paolo Strazzolini

  DOI：10.1016/s0040-4020(01)81940-2

  日期：1991.9

  nitrosation was never observed, but minor amounts of m- and p-nitro amines and/or nitrosamines were formed in some cases. Ring nitration is rather a reaction of the initial substrate than a process occurring on formed nitrosamines. The leaving propensities of the initial N-substituents to yield nitrosamines were in the order benzyl methyl alkyl.

  在回流温度下，通过亚硝酸正丁酯/氯化铵/水将具有各种环取代基的N，N-二烷基芳族胺有效地进行N-脱烷基化和N-亚硝化。从未观察到环亚硝化，但是在某些情况下会形成少量的间硝基和对硝基胺和/或亚硝胺。环硝化反应是初始底物的反应，而不是在形成的亚硝胺上发生的过程。起始N-取代基产生亚硝胺的离开倾向按苄基甲基烷基顺序排列。
• Reductive amination of ketones/aldehydes with amines using BH₃N(C₂H₅)₃ as a reductant
  作者：Qizhuang Zou、Fei Liu、Tianxiang Zhao、Xingbang Hu

  DOI：10.1039/d1cc02618f

  日期：——

  first example of efficient reductive amination of ketones/aldehydes with amines using BH3N(C2H5)3 as a catalyst and a reductant under mild conditions, affording various tertiary and secondary amines in excellent yields. A mechanistic study indicates that BH3N(C2H5)3 plays a dual function role of promoting imine and iminium formation and serving as a reductant in reductive amination.

  在此，我们报告了使用 BH 3 N(C 2 H 5 ) 3作为催化剂和还原剂在温和条件下用胺有效还原胺化酮/醛的第一个例子，以优异的产率提供各种叔胺和仲胺。机理研究表明，BH 3 N(C 2 H 5 ) 3具有促进亚胺和亚胺形成以及在还原胺化中作为还原剂的双重作用。
• Structure−Activity Relationships for the Antileishmanial and Antitrypanosomal Activities of 1‘-Substituted 9-Anilinoacridines
  作者：Swarna A. Gamage、David P. Figgitt、Stanley J. Wojcik、Raymond K. Ralph、Adriana Ransijn、Jacques Mauel、Vanessa Yardley、Diane Snowdon、Simon L. Croft、William A. Denny

  DOI：10.1021/jm970232h

  日期：1997.8.1

  Members of the class of 9-anilinoacridine topoisomerase II inhibitors bearing lipophilic electron-donating 1'-anilino substituents are active against both the promastigote and amastigote forms of the parasite Leishmania major. A series of analogues of the known 1'-NHhexyl lead compound were prepared and evaluated against L. major in macrophage culture to further develop structure-activity relationships (SAR). Toxicity toward mammalian cells was measured in a human leukemia cell line, and the ratio of the two IC50 values (IC50(J)/IC50(L)) was used as a measure of the in vitro therapeutic index (IVTI). A 3,6-diNMe(2) substitution pattern on the acridine greatly increased toxicity to L. major without altering mammalian toxicity, increasing IVTIs over that of the lead compound. The 2-OMe, 6-Cl acridine substitution pattern used in the antimalarial drug mepacrine also resulted in potent antileishmanial activity and high IVTIs. Earlier suggestions of the utility of 2'-OR groups in lowering mammalian cytotoxicity were not borne out in this wider study. A series of very lipophilic 1'-NRR (symmetric dialkylamino)-substituted analogues showed relatively high antileishmanial potency, but no clear trend was apparent across the series, and none were superior to the 1'-NH(CH2)(5)Me subclass. Subsets of the most active 1'-N(R)(CH2)(5)Me- and 1'-N(alkyl)(2)-substituted compounds against L. major were also evaluated against Leishmania donovani, Trypanosoma cruzi, and Trypanosoma brucei, but no consistent SAR could be discerned in these physiologically diverse test systems. The present study has confirmed earlier conclusions that lipophilic electron-donating groups at the 1'-position of 9-anilinoacridines provide high activity against L. major, but the SAR patterns observed do not carry over to the other parasites studied.