Identification of small molecule inhibitors of the hepatitis C virus RNA-dependent RNA polymerase from a pyrrolidine combinatorial mixture.
HTS of the compound collection for inhibition of the HCV RNA dependent RNA polymerase identified two 168 member N-acyl pyrrolidine combinatorial mixture hits. Deconvolution and expansion of these mixtures by solid phase synthesis to establish initial SAR and identify a potent inhibitor is reported.
Burton
George
G
GlaxoSmithKline Pharmaceuticals, 1250 South Collegeville Road, PO Box 5089, Collegeville, PA 19426-0989, USA. george.burton@gsk.com
Ku
Thomas W
TW
Carr
Thomas J
TJ
Kiesow
Terry
T
Sarisky
Robert T
RT
Lin-Goerke
Juili
J
Baker
Audrey
A
Earnshaw
David L
DL
Hofmann
Glenn A
GA
Keenan
Richard M
RM
Dhanak
Dashyant
D
D020650:Combinatorial Chemistry Techniques; D016174:Hepacivirus / Q000201:enzymology*; D015394:Molecular Structure; D011759:Pyrrolidines / Q000737:chemistry* / Q000494:pharmacology*; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors*
D011759:Pyrrolidines; D012324:RNA-Dependent RNA Polymerase