Cell-based medicinal chemistry optimization of high throughput screening hits for orally active antimalarials. Part 2: hits from SoftFocus kinase and other libraries.
In the second part of this Miniperspectives series, we highlight our medicinal chemistry efforts involving progression of hits from whole cell high-throughput screening (HTS) of a SoftFocus kinase library against the malaria parasite Plasmodium falciparum . Successful SAR exploration in Hit-to-Lead and Lead Optimization efforts leading to the selection of a preclinical development candidate are demonstrated. Related efforts by researchers from Broad/Genzyme, Anacor, and GSK are briefly covered.
Department of Chemistry, University of Cape Town , Rondebosch 7701, South Africa.
Yassir
Y
Younis
Leslie J
LJ
Street
David
D
Waterson
Michael J
MJ
Witty
Kelly
K
Chibale
D000284:Administration, Oral; D000962:Antimalarials / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D055808:Drug Discovery / Q000379:methods*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology / Q000517:prevention & control; D015394:Molecular Structure; D010963:Plasmodium falciparum / Q000187:drug effects; D013329:Structure-Activity Relationship
D000962:Antimalarials