Search for new pharmacophores for antimalarial activity. Part II: synthesis and antimalarial activity of new 6-ureido-4-anilinoquinazolines.
Synthesis of new 6-ureido-4-anilinoquinazolines have been accomplished and their in vitro antimalarial activity against chloroquine-sensitive P. falciparum have been examined. Out of 64 compounds evaluated, the IC(50) of 16 compounds which have displayed MIC of 0.25 microg/mL were also recorded. One of the compounds (24 g) had IC(50) value of 2.27 ng/mL which was equipotent to the standard drug chloroquine used in the bioassay. The in vivo evaluation of a few compounds among the series led to discovery of one analog (30 g) displaying 40% curative activity (28 days) against mdr P. yoeillinigeriensis at an oral dose of 100 mg/kg x 4 days.
Madapa
S
S
Medicinal and Process Chemistry Division, Central Drug Research Institute, PO Box 173, Lucknow 226001, India.
Tusi
Z
Z
Mishra
A
A
Srivastava
K
K
Pandey
S K
SK
Tripathi
R
R
Puri
S K
SK
Batra
S
S
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis*; D020128:Inhibitory Concentration 50; D008288:Malaria / Q000188:drug therapy; D010963:Plasmodium falciparum / Q000187:drug effects*; D010967:Plasmodium yoelii / Q000187:drug effects; D011799:Quinazolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
D000962:Antimalarials; D011799:Quinazolines