title: Design, synthesis, inhibitory activity, and SAR studies of hydrophobic p-aminosalicylic acid derivatives as neuraminidase inhibitors.
abstract: A series of hydrophobic p-aminosalicylic acid derivatives containing a lipophilic side chain at C-2 and an amino or guanidine at C-5 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 available p-aminosalicylic acid (PAS) using a suitable synthetic strategy. These compounds showed potent inhibitory activity against influenza A NA. Within this series, six compounds, 11, 12, 13e, 16e, 17c, and 18e, have the good potency (IC(50)=0.032-0.049 microM), which are compared to Oseltamivir (IC(50)=0.021 microM) and could be used as lead compounds in the future.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Shandong University, 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: D010131:Aminosalicylic Acid / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000636:Aminosalicylic Acids; D001665:Binding Sites; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D057927:Hydrophobic and Hydrophilic Interactions; D053122:Influenza A Virus, H3N2 Subtype / Q000201:enzymology*; D008958:Models, Molecular; D015394:Molecular Structure; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000636:Aminosalicylic Acids; D004791:Enzyme Inhibitors; D010131:Aminosalicylic Acid; D009439:Neuraminidase