N-[4-[(6-methoxyquinolin-8-yl)amino]pentyl]-4-[[(1R,4S,5R,8S,9R,10S,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-yl]oxymethyl]benzamide | 1519728-36-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: N-[4-[(6-methoxyquinolin-8-yl)amino]pentyl]-4-[[(1R,4S,5R,8S,9R,10S,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-yl]oxymethyl]benzamide
• CAS: 1519728-36-9
• 化学式: C₃₈H₄₉N₃O₇
• 分子量: 659.823
• InChiKey: CVHGDJACUJUWGU-AIJKMRHLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  48
• 可旋转键数：
  11
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  109
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  磷酸伯氨喹 、 蒿醚林酸 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以72%的产率得到N-[4-[(6-methoxyquinolin-8-yl)amino]pentyl]-4-[[(1R,4S,5R,8S,9R,10S,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-yl]oxymethyl]benzamide
  参考文献：
  名称：

  Novel Endoperoxide-Based Transmission-Blocking Antimalarials with Liver- and Blood-Schizontocidal Activities

  摘要：

  In a search for effective compounds against both the blood- and liver-stages of infection by malaria parasites with the ability to block the transmission of the disease to mosquito vectors, a series of hybrid compounds combining either a 1,2,4-trioxane or 1,2,4,5-tetraoxane and 8-aminoquinoline moieties were synthesized and screened for their antimalarial activity. These hybrid compounds showed high potency against both exoerythrocytic and erythrocytic forms of malaria parasites, comparable to representative trioxane-based counterparts. Furthermore, they efficiently blocked the development of the sporogonic cycle in the mosquito vector. The tetraoxane-based hybrid 5, containing an amide linker between the two moieties, effectively cleared a patent blood-stage P. berghei infection in mice after i.p. administration. Overall, these results indicate that peroxide-8-aminoquinoline hybrids are excellent starting points to develop an agent that conveys all the desired antimalarial multistage activities in a single chemical entity and, as such, with the potential to be used in malaria elimination campaigns.

  DOI：

  10.1021/ml4002985

文献信息

• Novel Endoperoxide-Based Transmission-Blocking Antimalarials with Liver- and Blood-Schizontocidal Activities
  作者：Daniela Miranda、Rita Capela、Inês S. Albuquerque、Patrícia Meireles、Isa Paiva、Fátima Nogueira、Richard Amewu、Jiri Gut、Philip J. Rosenthal、Rudi Oliveira、Maria M. Mota、Rui Moreira、Francesc Marti、Miguel Prudêncio、Paul M. O’Neill、Francisca Lopes

  DOI：10.1021/ml4002985

  日期：2014.2.13

  In a search for effective compounds against both the blood- and liver-stages of infection by malaria parasites with the ability to block the transmission of the disease to mosquito vectors, a series of hybrid compounds combining either a 1,2,4-trioxane or 1,2,4,5-tetraoxane and 8-aminoquinoline moieties were synthesized and screened for their antimalarial activity. These hybrid compounds showed high potency against both exoerythrocytic and erythrocytic forms of malaria parasites, comparable to representative trioxane-based counterparts. Furthermore, they efficiently blocked the development of the sporogonic cycle in the mosquito vector. The tetraoxane-based hybrid 5, containing an amide linker between the two moieties, effectively cleared a patent blood-stage P. berghei infection in mice after i.p. administration. Overall, these results indicate that peroxide-8-aminoquinoline hybrids are excellent starting points to develop an agent that conveys all the desired antimalarial multistage activities in a single chemical entity and, as such, with the potential to be used in malaria elimination campaigns.