Antimalarial cyclic peroxy ketals.
Over 20 new, cyclic, peroxy ketals have been prepared via a two-step protocol starting with readily available aryl methyl ketones. Structure-activity correlations using in vitro antimalarial data as a guide for optimization of potency have led to the design and synthesis of seven new peroxides that have IC50 values of 31-85 nM (artemisinin IC50 = 8.4 nM). Some SAR generalizations are discussed.
Posner
G H
GH
Department of Chemistry, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
O'Dowd
H
H
Ploypradith
P
P
Cumming
J N
JN
Xie
S
S
Shapiro
T A
TA
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D037621:Artemisinins; D015195:Drug Design; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects; D012717:Sesquiterpenes / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000962:Antimalarials; D037621:Artemisinins; D006571:Heterocyclic Compounds; D012717:Sesquiterpenes; C031327:artemisinin