Discovery of novel 1H-imidazol-2-yl-pyrimidine-4,6-diamines as potential antimalarials.
A novel family of 1H-imidazol-2-yl-pyrimidine-4,6-diamines has been identified with potent activity against the erythrocyte-stage of Plasmodium falciparum (Pf), the most common causative agent of malaria. A systematic SAR study resulted in the identification of compound 40 which exhibits good potency against both wild-type and drug resistant parasites and exhibits good in vivo pharmacokinetic properties.
Deng
Xianming
X
Department of Biological Chemistry & Molecular Pharmacology, Harvard Medical School, 250 Longwood Ave., SGM 628, Boston, MA 02115, USA.
Nagle
Advait
A
Wu
Tao
T
Sakata
Tomoyo
T
Henson
Kerstin
K
Chen
Zhong
Z
Kuhen
Kelli
K
Plouffe
David
D
Winzeler
Elizabeth
E
Adrian
Francisco
F
Tuntland
Tove
T
Chang
Jonathan
J
Simerson
Susan
S
Howard
Steven
S
Ek
Jared
J
Isbell
John
J
Tully
David C
DC
Chatterjee
Arnab K
AK
Gray
Nathanael S
NS
D000818:Animals; D000962:Antimalarials / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D055808:Drug Discovery; D010963:Plasmodium falciparum / Q000187:drug effects*; D011743:Pyrimidines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000962:Antimalarials; D011743:Pyrimidines