ANTIMALARIAL-DRUGS .64. SYNTHESIS AND ANTIMALARIAL PROPERTIES OF 1-IMINO DERIVATIVES OF 7-CHLORO-3-SUBSTITUTED-3,4-DIHYDRO-1,9(2H,10H)-ACRIDINEDIONES AND RELATED STRUCTURES
ANTIMALARIAL-DRUGS .64. SYNTHESIS AND ANTIMALARIAL PROPERTIES OF 1-IMINO DERIVATIVES OF 7-CHLORO-3-SUBSTITUTED-3,4-DIHYDRO-1,9(2H,10H)-ACRIDINEDIONES AND RELATED STRUCTURES
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DOI：
10.1021/jm00097a001
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发表时间：
1992-09-18
影响因子：
7.3
通讯作者：
WERBEL, LM
中科院分区：
文献类型：
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作者：
KESTEN, SJ;DEGNAN, MJ;WERBEL, LM
为了提高3-芳基-7-氯-3，4-二氢-1，9（2 H，10 H）-吖啶二酮的活性和性质，制备了多种1-[（烷氨基）亚烷基]亚氨基衍生物（3），并在啮齿类和灵长类动物中显示出高活性的抗疟剂。在所制备的结构修饰中，包括N-10-烷基和C2-取代的类似物，除去C-9氧，以及在C-9引入亚氨基侧链，N-10-H吖啶二酮的亚胺是所获得的最具活性的化合物。7-氯-3-（2，4-二氯苯基）-3，4-二氢-1，9（2 H，10 H）-吖啶二酮（9aa）的[3-（N，N-二甲基氨基）丙基]亚氨基衍生物在灵长类动物的高级研究中被证明具有高度活性。
To improve upon the activity and properties of the 3-aryl-7-chloro-3,4-dihydro-1,9(2H,10H)-acridinediones, a variety of 1-[(alkylamino)alkylene]imino derivatives (3) were prepared and shown to be highly active antimalarial agents in both rodents and primates. Among structural modifications prepared, including N-10-alkyl and C2-substituted analogs, removal of the C-9 oxygen, and introduction of an imino side chain at C-9, the imines of the N-10-H acridinediones were the most active compounds obtained. The [3-(NN-dimethylamino)propyl]imino derivative of 7-chloro-3-(2,4-dichlorophenyl)-3,4-dihydro-1,9(2H,10H)-acridinedione (9aa) proved to be highly active in advanced studies in primates.