title: Design, synthesis, inhibitory activity, and SAR studies of pyrrolidine derivatives as neuraminidase inhibitors.
abstract: A series of pyrrolidine derivatives were synthesized and evaluated for their ability to inhibit neuraminidase (NA) of influenza A virus (H3N2). All compounds were synthesized in good yields starting from commercially 4-hydroxy-L-proline using a suitable synthetic strategy. These compounds showed potent inhibitory activity against influenza A neuraminidase. Within this series, five compounds, 6e, 9c, 9e, 9f, and 10e, have good potency (IC(50)=1.56-2.71 microM) which are compared to that the NA inhibitor Oseltamivir (IC(50)=1.06 microM), and could be used as lead compoundS in the future.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Shandong University, 44, Wenhuaxi Road, Ji'nan, Shandong 250012, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Hao
authors.initials: H
authors.lastname: Fang
authors.forename: Wenfang
authors.initials: W
authors.lastname: Xu
authors.forename: Ailin
authors.initials: A
authors.lastname: Liu
authors.forename: Guanhua
authors.initials: G
authors.lastname: Du
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D004008:Diclofenac / Q000494:pharmacology; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006909:Hydroxyproline / Q000737:chemistry / Q000494:pharmacology; D007202:Indicators and Reagents; D053122:Influenza A Virus, H3N2 Subtype / Q000187:drug effects / Q000201:enzymology*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D011759:Pyrrolidines; D004008:Diclofenac; D009439:Neuraminidase; D006909:Hydroxyproline