Synthesis and antimalarial properties of 1-imino derivatives of 7-chloro-3-substituted-3,4-dihydro-1,9(2H,10H)-acridinediones and related structures.
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.
Kesten
S J
SJ
Warner-Lambert/Parke-Davis Pharmaceutical Research, Ann Arbor, Michigan 48105.
Degnan
M J
MJ
Hung
J
J
McNamara
D J
DJ
Ortwine
D F
DF
Uhlendorf
S E
SE
Werbel
L M
LM
D000166:Acridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D000882:Haplorhini; D008288:Malaria / Q000188:drug therapy; D051379:Mice; D010962:Plasmodium berghei / Q000187:drug effects; D013329:Structure-Activity Relationship
D000166:Acridines; D000962:Antimalarials; C073155:WR 243251; C022008:floxacrine