title: Design, synthesis, and structural analysis of inhibitors of influenza neuraminidase containing a 2,3-disubstituted tetrahydrofuran-5-carboxylic acid core.
abstract: (+/-)-(2R,3R,5R)-[2-(1'-S-acetamido-3'-methyl)butyl-3-methoxycarbonyl]tetrahydrofuran-5-carboxylic acid (9) and (+/-)-(2R,3R,5R)-[2-(1'-S-acetamido-3'-methyl)butyl-3-(4'-imidazolyl)]tetrahydrofuran 5-carboxylic acid (14) were synthesized as inhibitors of influenza neuraminidase (NA). Both compounds 9 and 14 inhibit influenza NA A with an IC(50) of about 0.5 microM and NA B with an IC(50) of 1.0 microM.
authors.affiliation: Global Pharmaceutical Research & Development, Abbott Laboratories, Abbott Park, IL 60064, USA. gary.t.wang@abbott.com
authors.forename: Gary T
authors.initials: GT
authors.lastname: Wang
authors.forename: Sheldon
authors.initials: S
authors.lastname: Wang
authors.forename: Robert
authors.initials: R
authors.lastname: Gentles
authors.forename: Thomas
authors.initials: T
authors.lastname: Sowin
authors.forename: Clarence J
authors.initials: CJ
authors.lastname: Maring
authors.forename: Dale J
authors.initials: DJ
authors.lastname: Kempf
authors.forename: Warren M
authors.initials: WM
authors.lastname: Kati
authors.forename: Vincent
authors.initials: V
authors.lastname: Stoll
authors.forename: Kent D
authors.initials: KD
authors.lastname: Stewart
authors.forename: Graeme
authors.initials: G
authors.lastname: Laver
mesh_terms: D002264:Carboxylic Acids / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D005663:Furans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular; D015394:Molecular Structure; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D009975:Orthomyxoviridae / Q000201:enzymology*
chemical_list: D002264:Carboxylic Acids; D004791:Enzyme Inhibitors; D005663:Furans; D009439:Neuraminidase