title: Synthesis and biological activity of macrocyclic inhibitors of hepatitis C virus (HCV) NS3 protease.
abstract: The 17-membered phenylalanine-based macrocycle 6 was prepared starting from 3-iodo-phenylalanine. Macrocyclization of alkene phenyl iodide 5 was effected through a palladium-catalyzed Heck reaction. The macrocyclic alpha-ketoamides were active inhibitors of the HCV NS3 protease, with the C-terminal acids and amides being more potent than tert-butyl esters.
authors.affiliation: Schering-Plough Research Institute, 2015 Galloping Hill Road, K-15-3-3545, Kenilworth, NJ 07033, USA. kevin.chen@spcorp.com
authors.forename: Kevin X
authors.initials: KX
authors.lastname: Chen
authors.forename: F George
authors.initials: FG
authors.lastname: Njoroge
authors.forename: Andrew
authors.initials: A
authors.lastname: Prongay
authors.forename: John
authors.initials: J
authors.lastname: Pichardo
authors.forename: Vincent
authors.initials: V
authors.lastname: Madison
authors.forename: Viyyoor
authors.initials: V
authors.lastname: Girijavallabhan
mesh_terms: D018360:Crystallography, X-Ray; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D011480:Protease Inhibitors; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases