N¹-((1-tert-butyl-1H-tetrazol-5-yl)(4-chlorophenyl)methyl)-N²-(7-chloroquinolin-4-yl)ethane-1,2-diamine | 1449333-81-6

• 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: N¹-((1-tert-butyl-1H-tetrazol-5-yl)(4-chlorophenyl)methyl)-N²-(7-chloroquinolin-4-yl)ethane-1,2-diamine
• 英文别名: N-{2-[(1-tert-butyl-1H-tetrazol-5-yl)(4-chlorophenyl)methylamino]ethyl}-7-chloroquinolin-4-amine；N'-[(1-tert-butyltetrazol-5-yl)-(4-chlorophenyl)methyl]-N-(7-chloro-4-quinolyl)ethane-1,2-diamine；N'-[(1-tert-butyltetrazol-5-yl)-(4-chlorophenyl)methyl]-N-(7-chloroquinolin-4-yl)ethane-1,2-diamine
• CAS: 1449333-81-6
• 化学式: C₂₃H₂₅Cl₂N₇
• 分子量: 470.404
• InChiKey: IHDMNALHWVSDJE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  80.6
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N¹-((1-tert-butyl-1H-tetrazol-5-yl)(4-chlorophenyl)methyl)-N²-(7-chloroquinolin-4-yl)ethane-1,2-diamine 在 盐酸 、 水 作用下， 以27%的产率得到N-{2-[(4-chlorophenyl)(1H-tetrazol-5-yl)methylamino]ethyl}-7-chloroquinolin-4-amine
  参考文献：
  名称：

  Synthesis and in Vitro and in Vivo Pharmacological Evaluation of New 4-Aminoquinoline-Based Compounds

  摘要：

  A new class of 4-aminoquinolines was synthesized and evaluated in vitro for antiplasmodial activity against both, the chloroquine-sensitive (3D7) and -resistant (K1 and W2) strains. The most active compounds 3c-3e had acceptable cytotoxicity but showed strong inhibition toward a panel of cytochrome P450 enzymes in vitro. Pharmacokinetic studies on 3d and 3e in mice showed that they had moderate half-life (4-6 h) and low oral bioavailability. The front runner compound 3d exhibited moderate inhibition of the malaria parasite on P. berghei infected mice following oral administration (5 mg/kg), achieving reduction of parasitemia population by 47% on day 7.

  DOI：

  10.1021/ml400311r
• 作为产物：
  描述：

  4-(2-氨基乙基)氨基-7-氯喹啉 在 叠氮基三甲基硅烷 作用下， 以 甲醇 为溶剂， 反应 24.08h， 生成 N¹-((1-tert-butyl-1H-tetrazol-5-yl)(4-chlorophenyl)methyl)-N²-(7-chloroquinolin-4-yl)ethane-1,2-diamine
  参考文献：
  名称：

  Synthesis and in Vitro and in Vivo Pharmacological Evaluation of New 4-Aminoquinoline-Based Compounds

  摘要：

  A new class of 4-aminoquinolines was synthesized and evaluated in vitro for antiplasmodial activity against both, the chloroquine-sensitive (3D7) and -resistant (K1 and W2) strains. The most active compounds 3c-3e had acceptable cytotoxicity but showed strong inhibition toward a panel of cytochrome P450 enzymes in vitro. Pharmacokinetic studies on 3d and 3e in mice showed that they had moderate half-life (4-6 h) and low oral bioavailability. The front runner compound 3d exhibited moderate inhibition of the malaria parasite on P. berghei infected mice following oral administration (5 mg/kg), achieving reduction of parasitemia population by 47% on day 7.

  DOI：

  10.1021/ml400311r

文献信息

• Synthesis and bioevaluation of novel 4-aminoquinoline-tetrazole derivatives as potent antimalarial agents
  作者：Shashi Pandey、Pooja Agarwal、Kumkum Srivastava、S. RajaKumar、Sunil K. Puri、Pravesh Verma、J.K. Saxena、Abhisheak Sharma、Jawahar Lal、Prem M.S. Chauhan

  DOI：10.1016/j.ejmech.2013.05.023

  日期：2013.8

  A series of novel tetrazole derivatives of 4-aminoquinoline were synthesized and screened for their antimalarial activities against both chloroquine-senstive (3D7) and chloroquine-resistant (K1) strains of Plasmodium falciparum as well as for cytotoxicity against VERO cell lines. Most of the synthesized compounds exhibited potent antimalarial activity as compared to chloroquine against K1-strain. Compounds with significant in vitro antimalarial activity were then evaluated for their in vivo efficacy in Swiss mice against Plasmodium yoelii following both intraperitoneal (ip) and oral administration, wherein compounds 20 and 23 each showed in vivo suppression of 99.99% parasitaemia on day 4. (C) 2013 Elsevier Masson SAS. All rights reserved.
• Synthesis and in Vitro and in Vivo Pharmacological Evaluation of New 4-Aminoquinoline-Based Compounds
  作者：Matshawandile Tukulula、Mathew Njoroge、Efrem T. Abay、Grace C. Mugumbate、Lubbe Wiesner、Dale Taylor、Liezl Gibhard、Jennifer Norman、Kenneth J. Swart、Jiri Gut、Philip J. Rosenthal、Samuel Barteau、Judith Streckfuss、Jacques Kameni-Tcheudji、Kelly Chibale

  DOI：10.1021/ml400311r

  日期：2013.12.12

  A new class of 4-aminoquinolines was synthesized and evaluated in vitro for antiplasmodial activity against both, the chloroquine-sensitive (3D7) and -resistant (K1 and W2) strains. The most active compounds 3c-3e had acceptable cytotoxicity but showed strong inhibition toward a panel of cytochrome P450 enzymes in vitro. Pharmacokinetic studies on 3d and 3e in mice showed that they had moderate half-life (4-6 h) and low oral bioavailability. The front runner compound 3d exhibited moderate inhibition of the malaria parasite on P. berghei infected mice following oral administration (5 mg/kg), achieving reduction of parasitemia population by 47% on day 7.