2,8-二(三氟甲基)-4-(哌嗪-1-基)喹啉 | 401567-76-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 2,8-二(三氟甲基)-4-(哌嗪-1-基)喹啉
• 英文名称: 4-(piperazin-1-yl)-2,8-bis(trifluoromethyl)quinoline
• 英文别名: 2,8-Bis(trifluoromethyl)-4-(piperazin-1-yl)quinoline；4-piperazin-1-yl-2,8-bis(trifluoromethyl)quinoline
• CAS: 401567-76-8
• 化学式: C₁₅H₁₃F₆N₃
• 分子量: 349.279
• InChiKey: MIGQWBMOCOHDID-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  24
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  28.2
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2,8-二(三氟甲基)-4-(哌嗪-1-基)喹啉 、 邻溴苯甲醛 在 sodium cyanoborohydride 作用下， 以 甲醇 为溶剂， 反应 6.0h， 以59%的产率得到
  参考文献：
  名称：

  Arylpiperazines displaying preferential potency against chloroquine-resistant strains of the malaria parasite Plasmodium falciparum

  摘要：

  Arylpiperazines in which the terminal secondary amino group is unsubstituted were found to display a mefloquine-type antimalarial behavior in being significantly more potent against the chloroquine-resistant (W2 and FCR3) strains of Plasmodium falciparum than against the chloroquine-sensitive (D10 and NF54) strains. Substitution of the aforementioned amino group led to a dramatic drop in activity across all strains as well as abolition of the preferential potency against resistant strains that was observed for the unsubstituted counterparts. The data suggest that unsubstituted arylpiperazines are not well-recognized by the chloroquine resistance mechanism and may imply that they act mechanistically differently from chloroquine. On the other hand, 4-aminoquinoline-based heteroarylpiperazines in which the terminal secondary amino group is also unsubstituted, were found to be equally active against the chloroquine -resistant and chloroquine-sensitive strains, suggesting that chloroquine cross-resistance is not observed with these two 4-aminoquinolines. In contrast, two 4-aminoquinoline-based heteroarylpiperazines are positively recognized by the chloroquine resistance mechanism. These studies provide structural features that determine the antimalarial activity of arylpiperazines for further development, particularly against chloroquine-resistant strains. (c) 2005 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bcp.2005.10.023
• 作为产物：
  描述：

  2,8-双(三氟甲基)-4-羟基喹啉 在 sodium hydride 、 三氯氧磷 作用下， 以 二甲基亚砜 、 mineral oil 为溶剂， 反应 29.25h， 生成 2,8-二(三氟甲基)-4-(哌嗪-1-基)喹啉
  参考文献：
  名称：

  新的杂合三氟甲基喹啉类作为抗疟原虫剂。

  摘要：

  疟疾仍然是全球范围内的主要公共卫生问题，是造成高发病率和高死亡率的原因。已经确定了对当前抗疟药的耐药性，并且迫切需要新药。在这项研究中，我们基于甲氟喹（（2,8-双（三氟甲基）喹啉-4-基）（哌啶-2-基）甲醇）和氨二喹（4-（（7 -氯喹啉-4-基）氨基）-2-（（二乙基氨基）甲基）苯酚）使用环生物等位取代和官能团的分子杂交。在体外针对恶性疟原虫和在感染伯氏疟原虫的小鼠体内评估了该化合物。所有衍生物均呈现抗-P。恶性疟原虫活性，IC50值为0.083至33.0 µM。具有最佳抗P的化合物。恶性疟原虫活性为N-（5-甲基-4H-1,2，4-三唑-3-基）-2,8-双（三氟甲基）喹啉-4-胺（12）的IC50为0.083 µM。选择三种活性最高的化合物用于针对伯氏疟原虫感染的小鼠的抗疟活性测试。化合物12在感染后第5天最活跃，可将寄生虫病降低66％，这与其体外活性是一致的。这是一个重要的结果

  DOI：

  10.1016/j.bmc.2019.01.044

文献信息

• Proline derivatives and use thereof as drugs
  申请人：Kitajima Hiroshi

  公开号：US20050245538A1

  公开（公告）日：2005-11-03

  The present invention aims at providing compounds having therapeutic effects due to a DPP-IV inhibitory action, and satisfactory as pharmaceutical products. The present inventors have found that derivatives having a substituent introduced into the γ-position of proline represented by the formula (I) wherein each symbol is as defined in the specification, have a potent DPP-IV inhibitory activity, and completed the present invention by increasing the stability.

  本发明旨在提供具有治疗效果的化合物，其作用是通过DPP-IV的抑制作用，并且作为药物产品具有令人满意的效果。本发明人发现，在丙氨酸的γ位上引入取代基的衍生物具有强效的DPP-IV抑制活性，并通过增加稳定性完成了本发明。
• Proline derivatives and the use thereof as drugs
  申请人：——

  公开号：US20040106655A1

  公开（公告）日：2004-06-03

  The present invention aims at providing compounds having therapeutic effects due to a DPP-IV inhibitory action, and satisfactory as pharmaceutical products. The present inventors have found that derivatives having a substituent introduced into the &ggr;-position of proline represented by the formula (I) 1 wherein each symbol is as defined in the specification, have a potent DPP-IV inhibitory activity, and completed the present invention by increasing the stability.

  本发明旨在提供具有治疗作用的化合物，由于DPP-IV抑制作用而具有满意的药物产品。本发明人发现，具有引入取代基的脯氨酸γ-位置的衍生物，其化学式为(I)1，其中每个符号如规范中所定义，具有强效的DPP-IV抑制活性，并通过增加稳定性完成了本发明。
• PROLINE DERIVATIVES AND USE THEREOF AS DRUGS
  申请人：Mitsubishi Tanabe Pharma Corporation

  公开号：EP1308439B1

  公开（公告）日：2008-10-15
• US7060722B2
  申请人：——

  公开号：US7060722B2

  公开（公告）日：2006-06-13
• US7074794B2
  申请人：——

  公开号：US7074794B2

  公开（公告）日：2006-07-11