(E)-4-(2-chlorophenyl)-N,N-dimethyl-4-(2-pyridyl)but-3-en-1-ammonium trifluoroacetate | 1585241-40-2

• 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: (E)-4-(2-chlorophenyl)-N,N-dimethyl-4-(2-pyridyl)but-3-en-1-ammonium trifluoroacetate
• CAS: 1585241-40-2
• 化学式: C₂HF₃O₂*C₁₇H₁₉ClN₂
• 分子量: 400.828
• InChiKey: QROMNQDKRBVEQI-NSPIFIKESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.75
• 重原子数：
  27.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  53.43
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (E)-4-(2-chlorophenyl)-N,N-dimethyl-4-(2-pyridyl)but-3-en-1-ammonium trifluoroacetate 、 三氟乙酸 在 5%-palladium/activated carbon 、 氢气 作用下， 以 乙醇 、 水 为溶剂， 反应 13.0h， 生成 dimethyl-(4-phenyl-4-[2]pyridyl-butyl)-amine 、 4-(2-chlorophenyl)-N,N-dimethyl-4-(2-pyridyl)but-3-en-1-ammonium trifluoroacetate
  参考文献：
  名称：

  Chlorpheniramine Analogues Reverse Chloroquine Resistance in Plasmodium falciparum by Inhibiting PfCRT

  摘要：

  The emergence and spread of malaria parasites that are resistant to chloroquine (CQ) has been a disaster for world health. The antihistamine chlorpheniramine (CP) partially resensitizes CQ-resistant (CQR) parasites to CQ but possesses little intrinsic antiplasmodial activity. Mutations in the parasite's CQ resistance transporter (PfCRT) confer resistance to CQ by enabling the protein to transport the drug away from its site of action, and it is thought that resistance-reversers such as CP exert their effect by blocking this CQ transport activity. Here, a series of new structural analogues and homologues of CP have been synthesized. We show that these compounds (along with other in vitro CQ resistance-reversers) inhibit the transport of CQ via a resistance-conferring form of PfCRT expressed in Xenopus laevis oocytes. Furthermore, the level of PfCRT-inhibition was found to correlate well with both the restoration of CQ accumulation and the level of CQ resensitization in CQR parasites.

  DOI：

  10.1021/ml5000228
• 作为产物：
  描述：

  2-氯苯甲酸甲酯 在 正丁基锂 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙醚 、 环己烷 为溶剂， 反应 48.5h， 生成 (E)-4-(2-chlorophenyl)-N,N-dimethyl-4-(2-pyridyl)but-3-en-1-ammonium trifluoroacetate
  参考文献：
  名称：

  Chlorpheniramine Analogues Reverse Chloroquine Resistance in Plasmodium falciparum by Inhibiting PfCRT

  摘要：

  The emergence and spread of malaria parasites that are resistant to chloroquine (CQ) has been a disaster for world health. The antihistamine chlorpheniramine (CP) partially resensitizes CQ-resistant (CQR) parasites to CQ but possesses little intrinsic antiplasmodial activity. Mutations in the parasite's CQ resistance transporter (PfCRT) confer resistance to CQ by enabling the protein to transport the drug away from its site of action, and it is thought that resistance-reversers such as CP exert their effect by blocking this CQ transport activity. Here, a series of new structural analogues and homologues of CP have been synthesized. We show that these compounds (along with other in vitro CQ resistance-reversers) inhibit the transport of CQ via a resistance-conferring form of PfCRT expressed in Xenopus laevis oocytes. Furthermore, the level of PfCRT-inhibition was found to correlate well with both the restoration of CQ accumulation and the level of CQ resensitization in CQR parasites.

  DOI：

  10.1021/ml5000228