N-[(4-chloropyridin-3-yl)methyl]-N'-(7-chloroquinolin-4-yl)-ethane-1,2-diamine | 1447024-47-6

• 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: N-[(4-chloropyridin-3-yl)methyl]-N'-(7-chloroquinolin-4-yl)-ethane-1,2-diamine
• 英文别名: N-[(4-chloropyridin-3-yl)methyl]-N'-(7-chloroquinolin-4-yl)ethane-1,2-diamine
• CAS: 1447024-47-6
• 化学式: C₁₇H₁₆Cl₂N₄
• 分子量: 347.247
• InChiKey: VBNLJNPWSKEYCA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  49.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-[(4-chloropyridin-3-yl)methyl]-N'-(7-chloroquinolin-4-yl)-ethane-1,2-diamine 、 sodium methylate 在 溶剂黄146 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以85%的产率得到N-(7-chloroquinolin-4-yl)-N'-[(4-methoxypyridin-3-yl)-methyl]ethane-1,2-diamine
  参考文献：
  名称：

  4-Amino-7-chloroquinolines: Probing Ligand Efficiency Provides Botulinum Neurotoxin Serotype A Light Chain Inhibitors with Significant Antiprotozoal Activity

  摘要：

  Structurally simplified analogues of dual antimalarial and botulinum neurotoxin serotype A light chain (BoNT/A LC) inhibitor bis-aminoquinoline (1) were prepared. New compounds were designed to improve ligand efficiency while maintaining or exceeding the inhibitory potency of 1. Three of the new compounds are more active than 1 against both indications. Metabolically, the new inhibitors are relatively stable and nontoxic. 12, 14, and 15 are more potent BoNT/A LC inhibitors than 1. Additionally, 15 has excellent in vitro antimalarial efficacy, with IC90 values ranging from 4.45 to 12.11 nM against five Plasmodium falciparum (Pf) strains: W2, D6, C235, C2A, and C2B. The results indicate that the same level of inhibitory efficacy provided by 1 can be retained/exceeded with less structural complexity. 12, 14, and 15 provide new platforms for the development of more potent dual BoNT/A LC and P.f. inhibitors adhering to generally accepted chemical properties associated with the druggability of synthetic molecules.

  DOI：

  10.1021/jm4006077
• 作为产物：
  描述：

  4-(2-氨基乙基)氨基-7-氯喹啉 、 4-氯吡啶-3-甲醛 在 溶剂黄146 、 sodium tetrahydroborate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 20.5h， 以41%的产率得到N-[(4-chloropyridin-3-yl)methyl]-N'-(7-chloroquinolin-4-yl)-ethane-1,2-diamine
  参考文献：
  名称：

  4-Amino-7-chloroquinolines: Probing Ligand Efficiency Provides Botulinum Neurotoxin Serotype A Light Chain Inhibitors with Significant Antiprotozoal Activity

  摘要：

  Structurally simplified analogues of dual antimalarial and botulinum neurotoxin serotype A light chain (BoNT/A LC) inhibitor bis-aminoquinoline (1) were prepared. New compounds were designed to improve ligand efficiency while maintaining or exceeding the inhibitory potency of 1. Three of the new compounds are more active than 1 against both indications. Metabolically, the new inhibitors are relatively stable and nontoxic. 12, 14, and 15 are more potent BoNT/A LC inhibitors than 1. Additionally, 15 has excellent in vitro antimalarial efficacy, with IC90 values ranging from 4.45 to 12.11 nM against five Plasmodium falciparum (Pf) strains: W2, D6, C235, C2A, and C2B. The results indicate that the same level of inhibitory efficacy provided by 1 can be retained/exceeded with less structural complexity. 12, 14, and 15 provide new platforms for the development of more potent dual BoNT/A LC and P.f. inhibitors adhering to generally accepted chemical properties associated with the druggability of synthetic molecules.

  DOI：

  10.1021/jm4006077

文献信息

• 4-Amino-7-chloroquinolines: Probing Ligand Efficiency Provides Botulinum Neurotoxin Serotype A Light Chain Inhibitors with Significant Antiprotozoal Activity
  作者：Igor M. Opsenica、Mikloš Tot、Laura Gomba、Jonathan E. Nuss、Richard J. Sciotti、Sina Bavari、James C. Burnett、Bogdan A. Šolaja

  DOI：10.1021/jm4006077

  日期：2013.7.25

  Structurally simplified analogues of dual antimalarial and botulinum neurotoxin serotype A light chain (BoNT/A LC) inhibitor bis-aminoquinoline (1) were prepared. New compounds were designed to improve ligand efficiency while maintaining or exceeding the inhibitory potency of 1. Three of the new compounds are more active than 1 against both indications. Metabolically, the new inhibitors are relatively stable and nontoxic. 12, 14, and 15 are more potent BoNT/A LC inhibitors than 1. Additionally, 15 has excellent in vitro antimalarial efficacy, with IC90 values ranging from 4.45 to 12.11 nM against five Plasmodium falciparum (Pf) strains: W2, D6, C235, C2A, and C2B. The results indicate that the same level of inhibitory efficacy provided by 1 can be retained/exceeded with less structural complexity. 12, 14, and 15 provide new platforms for the development of more potent dual BoNT/A LC and P.f. inhibitors adhering to generally accepted chemical properties associated with the druggability of synthetic molecules.