title: Hexahydro-pyrrolo- and hexahydro-1H-pyrido[1,2-b]pyridazin-2-ones as potent inhibitors of HCV NS5B polymerase.
abstract: Hexahydro-pyrrolo- and hexahydro-1H-pyrido[1,2-b]pyridazin-2-one analogs were discovered as a novel class of inhibitors of genotype 1 HCV NS5B polymerase. Among these, compound 4c displayed potent inhibitory activities in biochemical and replicon assays (IC(50) (1b) <10 nM; EC(50) (1b)=34 nM) as well as good stability towards human liver microsomes (HLM t(1/2) =59 min).
authors: Anadys Pharmaceuticals, Inc., 3115 Merryfield Row, San Diego, CA 92121, USA. fruebsam@anadyspharma.com
authors: Frank
authors: F
authors: Ruebsam
authors: Zhongxiang
authors: Z
authors: Sun
authors: Benjamin K
authors: BK
authors: Ayida
authors: Stephen E
authors: SE
authors: Webber
authors: Yuefen
authors: Y
authors: Zhou
authors: Qiang
authors: Q
authors: Zhao
authors: Charles R
authors: CR
authors: Kissinger
authors: Richard E
authors: RE
authors: Showalter
authors: Amit M
authors: AM
authors: Shah
authors: Mei
authors: M
authors: Tsan
authors: Rupal
authors: R
authors: Patel
authors: Laurie A
authors: LA
authors: Lebrun
authors: Ruhi
authors: R
authors: Kamran
authors: Maria V
authors: MV
authors: Sergeeva
authors: Darian M
authors: DM
authors: Bartkowski
authors: Thomas G
authors: TG
authors: Nolan
authors: Daniel A
authors: DA
authors: Norris
authors: Leo
authors: L
authors: Kirkovsky
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D018360:Crystallography, X-Ray; D015195:Drug Design; D016174:Hepacivirus / Q000187:drug effects*; D006801:Humans; D008862:Microsomes, Liver / Q000187:drug effects*; D015394:Molecular Structure; D011724:Pyridazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D011724:Pyridazines; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase