Studies on acyl pyrrolidine inhibitors of HCV RNA-dependent RNA polymerase to identify a molecule with replicon antiviral activity.
The SAR development is described for a series of N-acyl pyrrolidine inhibitors of the Hepatitis C virus RNA-dependent RNA polymerase, NS5B, from tractable Delta21 enzyme inhibitors to an example with antiviral activity in a cellular assay (HCV replicon).
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
Hofmann
Glenn A
GA
Slater
Martin J
MJ
Haigh
David
D
Dhanak
Dashyant
D
Johnson
Victor K
VK
Parry
Nigel R
NR
Thommes
Pia
P
D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016174:Hepacivirus / Q000737:chemistry* / Q000235:genetics*; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D008968:Molecular Conformation; D011759:Pyrrolidines / Q000037:antagonists & inhibitors*; D012367:RNA, Viral / Q000737:chemistry; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors*; D012093:Replicon / Q000235:genetics*; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D011759:Pyrrolidines; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; C032519:pyrrolidine