title: Oseltamivir analogues bearing N-substituted guanidines as potent neuraminidase inhibitors.
abstract: A series of oseltamivir analogues bearing an N-substituted guanidine unit were prepared and evaluated as inhibitors of neuraminidases from four strains of influenza. The two most potent analogues identified contain relatively small N-guanidine substituents (N-methyl and N-hydroxyl) and display enhanced inhibition with IC50 values in the low nanomolar range against neuraminidases from wild-type and oseltamivir-resistant strains. Potential advantages of including the N-hydroxyguanidine moiety in neuraminidase inhibitors are also discussed.
authors.affiliation: Department of Medicinal Chemistry and Chemical Biology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University , Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.
authors.forename: Caitlin A
authors.initials: CA
authors.lastname: Mooney
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Johnson
authors.forename: Peter
authors.initials: P
authors.lastname: 't Hart
authors.forename: Linda
authors.initials: L
authors.lastname: Quarles van Ufford
authors.forename: Cornelis A M
authors.initials: CA
authors.lastname: de Haan
authors.forename: Ed E
authors.initials: EE
authors.lastname: Moret
authors.forename: Nathaniel I
authors.initials: NI
authors.lastname: Martin
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics; D006146:Guanidines / Q000737:chemistry*; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects*; D007251:Influenza, Human / Q000188:drug therapy / Q000821:virology; D008958:Models, Molecular; D015394:Molecular Structure; D009154:Mutation / Q000235:genetics; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D053139:Oseltamivir / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D006146:Guanidines; D053139:Oseltamivir; D009439:Neuraminidase