Design and synthesis of bicyclic pyrimidinone-based HCV NS3 protease inhibitors.
A series of bicyclic pyrimidinone-based HCV NS3 protease inhibitors was synthesized via selective C8 position functionalization. Substituted phenylamides and phenylureas were preferred in the S2 binding pocket.
Glunz
Peter W
PW
Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543-5400, USA. peter.glunz@bms.com
Douty
Brent D
BD
Decicco
Carl P
CP
D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology; D001549:Benzamides / Q000737:chemistry; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D010671:Phenylurea Compounds / Q000737:chemistry; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D000998:Antiviral Agents; D001549:Benzamides; D001643:Bridged Bicyclo Compounds; D010671:Phenylurea Compounds; D011744:Pyrimidinones; D012697:Serine Endopeptidases; D015842:Serine Proteinase Inhibitors; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases