New 4-aminoquinoline Mannich base antimalarials. 1. Effect of an alkyl substituent in the 5'-position of the 4'-hydroxyanilino side chain.
A new series of 4-aminoquinoline Mannich base derivatives have been synthesized, in which the 3'-diethylamino function of amodiaquine (AQ) is replaced by a 3'-tert-butylamino group and an aliphatic hydrocarbon entity is incorporated into the 5'-position of the 4'-hydroxyanilino side chain. Seven alkyl Mannich base derivatives were screened and found to be active against both chloroquine-sensitive and -resistant strains of Plasmodium falciparum in vitro. The propyl and isopropyl alkyl derivatives were found to be the most active; consequently these derivatives were tested against a nonsensitive strain of Plasmodium berghi in vivo and found to be 3-fold more active than AQ, irrespective of the route of administration (oral or intraperitoneal).
Raynes
K J
KJ
Departments of Pharmacology and Therapeutics and of Chemistry, The University of Liverpool, P.O. Box 147, Liverpool L69 3GE, U.K.
Stocks
P A
PA
O'Neill
P M
PM
Park
B K
BK
Ward
S A
SA
D000814:Aniline Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008288:Malaria / Q000188:drug therapy; D008297:Male; D008352:Mannich Bases / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D010962:Plasmodium berghei; D010963:Plasmodium falciparum / Q000187:drug effects; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000814:Aniline Compounds; D000962:Antimalarials; D008352:Mannich Bases; D011804:Quinolines