Synthesis and Antimalarial Properties of 1-Imino
Derivatives of
7-Chloro-3-substituted-3,4-dihydro-1,9(2H,10H)-acridin
ediones and Related Structures.
王惠珀
Kesten SJ;Degnan MJ;Hung Wang JHP;McNamara DJ;Ortwine
DF;Uhlendorf SE;Werbel LM
Abstract
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 N10-alkyl and C2-substituted analogs, removal of the C9 oxygen, and introduction of an imino side chain at C9, the imines of the N10-H acridinediones were the most active compounds obtained. The [3-(N,N- 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.