9-({4-[(N-pentylamino)methyl]phenyl}amino)acridine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 9-({4-[(N-pentylamino)methyl]phenyl}amino)acridine
• 英文别名: N-[4-[(pentylamino)methyl]phenyl]acridin-9-amine
• 化学式: C₂₅H₂₇N₃
• 分子量: 369.509
• InChiKey: DKIYQVPLLLIBAW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  37
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1-氨基戊烷 在 platinum on activated charcoal 盐酸 、 氢气 作用下， 以 甲醇 、 乙醇 、 水 为溶剂， 反应 1.5h， 生成 9-({4-[(N-pentylamino)methyl]phenyl}amino)acridine
  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

• 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.