(1R,2R)-N1,N2-bis(7-chloroquinolin-4-yl)cyclohexane-1,2-diamine

• 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: (1R,2R)-N1,N2-bis(7-chloroquinolin-4-yl)cyclohexane-1,2-diamine
• 英文别名: Ro 47-4577；Ro 48-6910；(1R,2R)-1-N,2-N-bis(7-chloroquinolin-4-yl)cyclohexane-1,2-diamine
• 化学式: C₂₄H₂₂Cl₂N₄
• 分子量: 437.371
• InChiKey: LISWOCWHIAZFSB-FGZHOGPDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  49.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4,7-二氯喹啉 、 trans-1,2-Diaminocyclohexane 在 三乙胺 作用下， 以 various solvent(s) 为溶剂， 以71%的产率得到(1R,2R)-N1,N2-bis(7-chloroquinolin-4-yl)cyclohexane-1,2-diamine
  参考文献：
  名称：

  Bisquinolines. 1. N,N-bis(7-chloroquinolin-4-yl)alkanediamines with potential against chloroquine-resistant malaria

  摘要：

  On the basis of observations that several bisquinolines such as piperaquine possess notable activity against chloroquine-resistant malaria, 13 N,N-bis-(7-chloroquinolin-4-yl)alkanediamines were synthesized and screened against Plasmodium falciparum in vitro and Plasmodium berghei in vivo. Twelve of the thirteen bisquinolines had a significantly lower resistance index than did chloroquine; the resistance index was apparently unrelated to either in vitro or in vivo activity. Except for two compounds, there was a reasonable correlation between in vitro and in vivo activities. Seven of the thirteen bisquinolines had IC50's of less than 6 nM against both chloroquine-sensitive (D-6) and -resistant (W-2) clones of P. falciparum and were curative against P. berghei at doses of 640 mg/kg. In contrast to chloroquine, these bisquinolines did not show any toxic deaths at curative dose levels. Four bisquinolines, however, caused skin lesions at the site of injection. Maximum activity was seen in bisquinolines with a connecting bridge of two carbon atoms where decreased conformational mobility seemed to increase activity. Bisquinoline 3 ((+/-)-trans-N1,N2-bis(7-chloroquinolin-4-yl)cyclohexane-1,2-diamine was not only the most potent bisquinoline in vitro, but was clearly unique in its in vivo activity-80% and 100% cure rates were achieved at doses of 160 and 320 mg/kg, respectively. In summary, these preliminary results support the premise that bisquinolines may be useful agents against chloroquine-resistant malaria.

  DOI：

  10.1021/jm00089a025

文献信息

• An Exploration of the Structure-activity Relationships of 4−Aminoquinolines: Novel Antimalarials with Activity In-vivo
  作者：F M D Ismail、M J DAscombe、P CArr、S E NOrth

  DOI：10.1111/j.2042-7158.1996.tb03985.x

  日期：2011.4.12

  The structure-activity relationships of bisquinolines, a potentially important group of novel antimalarial drugs, were studied. The high-temperature (180-250 degrees C) synthesis of 4-aminoquinolines, including bisquinolines, by nucleophilic displacement was both fast and efficient Several bisquinolines including (+/-)-trans-N1,N2-bis(7-trifluoroquinolin-4-yl)cyclohexane-1, 2-diamine and 1R,2R-(-)-

  研究了潜在的重要的新型抗疟药组双喹啉的构效关系。通过亲核取代反应，高温（180-250摄氏度）合成4-氨基喹啉，包括双喹啉既快速又有效。几种双喹啉包括（+/-）-反-N1，N2-双（7-三氟喹啉-4） -基）环己烷-1，2-二胺和1R，2R-（-）-，1S，2S-（+）-，（+/-）-反式和顺式N1，N2-双（7-氯喹啉- 4-基）环己烷-1，2-二胺对小鼠的伯氏疟原虫表现出有效的活性。（+/-）-反式-N1，N2-双（7-氯喹啉-4-基）环己烷-1，2-二胺具有口服活性。我们的结果表明，这些化合物符合喹啉抗疟药的假定受体。此外，在4位上通过杂环桥连接的7-卤代喹啉，
• ASYMMETRIC BISAMINOQUINOLINES AND BISAMINOQUINOLINES WITH VARIED LINKERS AS AUTOPHAGY INHIBITORS FOR CANCER AND OTHER THERAPY
  申请人：The Trustees of The University of Pennsylvania

  公开号：EP3848355A1

  公开（公告）日：2021-07-14

  The invention provides novel asymmetric and symmetric bisaminoquinolines and related compounds, methods of treatment and syntheses. The novel compounds exhibit effective anticancer activity and are useful in the treatment of a variety of autophagy-related disorders.

  本发明提供了新型不对称和对称双氨基喹啉及相关化合物、治疗方法和合成方法。这些新型化合物具有有效的抗癌活性，可用于治疗多种自噬相关疾病。
• Bisquinolines. 1. N,N-bis(7-chloroquinolin-4-yl)alkanediamines with potential against chloroquine-resistant malaria
  作者：Jonathan L. Vennerstrom、William Y. Ellis、Arba L. Ager、Steven L. Andersen、Lucia Gerena、Wilbur K. Milhous

  DOI：10.1021/jm00089a025

  日期：1992.5

  On the basis of observations that several bisquinolines such as piperaquine possess notable activity against chloroquine-resistant malaria, 13 N,N-bis-(7-chloroquinolin-4-yl)alkanediamines were synthesized and screened against Plasmodium falciparum in vitro and Plasmodium berghei in vivo. Twelve of the thirteen bisquinolines had a significantly lower resistance index than did chloroquine; the resistance index was apparently unrelated to either in vitro or in vivo activity. Except for two compounds, there was a reasonable correlation between in vitro and in vivo activities. Seven of the thirteen bisquinolines had IC50's of less than 6 nM against both chloroquine-sensitive (D-6) and -resistant (W-2) clones of P. falciparum and were curative against P. berghei at doses of 640 mg/kg. In contrast to chloroquine, these bisquinolines did not show any toxic deaths at curative dose levels. Four bisquinolines, however, caused skin lesions at the site of injection. Maximum activity was seen in bisquinolines with a connecting bridge of two carbon atoms where decreased conformational mobility seemed to increase activity. Bisquinoline 3 ((+/-)-trans-N1,N2-bis(7-chloroquinolin-4-yl)cyclohexane-1,2-diamine was not only the most potent bisquinoline in vitro, but was clearly unique in its in vivo activity-80% and 100% cure rates were achieved at doses of 160 and 320 mg/kg, respectively. In summary, these preliminary results support the premise that bisquinolines may be useful agents against chloroquine-resistant malaria.
• [EN] ANTIMALARIAL BISQUINOLINES
  申请人：BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA

  公开号：WO1993007126A1

  公开（公告）日：1993-04-15

  (EN) The present invention relates to new bisquinolines useful in the treatment of malaria and to processes for the production thereof. The invention also relates to methods for the treatment of malaria and, in particular, to the treatment of chloroquine-resistant strains of malaria. The compounds of the invention have following formula (I).(FR) L'invention concerne de nouvelles bisquinoléines utiles dans le traitement du paludisme ainsi que des procédés permettant leur production. L'invention concerne également des procédés de traitement du paludisme et notamment de traitement de souches de paludisme résistant à la chloroquine. Les composés de l'invention ont la formule (I).