title: Design, synthesis, and neuraminidase inhibitory activity of GS-4071 analogues that utilize a novel hydrophobic paradigm.
abstract: Structure-based design has led to the synthesis of a novel analogue of GS-4071, an influenza neuraminidase inhibitor, in which the basic amino group has been replaced by a hydrophobic vinyl group. An X-ray co-crystal structure of the new inhibitor (K(i)=45 nM) bound to the active site shows that the vinyl group occupies the same subsite as the amino group in GS-4071.
authors.affiliation: Department of Chemistry, Université de Montréal, QC, Canada. stephen.hanessian@umontreal.ca
authors.forename: Stephen
authors.initials: S
authors.lastname: Hanessian
authors.forename: Jianchio
authors.initials: J
authors.lastname: Wang
authors.forename: Debra
authors.initials: D
authors.lastname: Montgomery
authors.forename: Vincent
authors.initials: V
authors.lastname: Stoll
authors.forename: Kent D
authors.initials: KD
authors.lastname: Stewart
authors.forename: Warren
authors.initials: W
authors.lastname: Kati
authors.forename: Clarence
authors.initials: C
authors.lastname: Maring
authors.forename: Dale
authors.initials: D
authors.lastname: Kempf
authors.forename: Charles
authors.initials: C
authors.lastname: Hutchins
authors.forename: W Graeme
authors.initials: WG
authors.lastname: Laver
mesh_terms: D000081:Acetamides / Q000737:chemistry* / Q000494:pharmacology*; D000588:Amines / Q000737:chemistry; D015195:Drug Design; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D053139:Oseltamivir; D013329:Structure-Activity Relationship; D014753:Vinyl Compounds / Q000737:chemistry
chemical_list: D000081:Acetamides; D000588:Amines; D014753:Vinyl Compounds; D053139:Oseltamivir; D009439:Neuraminidase