Pyrrolidinobenzoic acid inhibitors of influenza virus neuraminidase: the hydrophobic side chain influences type A subtype selectivity.
Neuraminidase (NA) plays a critical role in the life cycle of influenza virus and is a target for new therapeutic agents. A series of influenza neuraminidase inhibitors with the pyrrolidinobenzoic acid scaffold containing lipophilic side chains at the C3 position have been synthesized and evaluated for influenza neuraminidase inhibitory activity. The size and geometry of the C3 side chains have been modified in order to investigate structure-activity relationships. The results indicated that size and geometry of the C3-side chain are important for selectivity of inhibition against N1 versus N2 NA, important type A influenza variants that infect man, including the highly lethal avian influenza.
Department of Chemistry, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Yanwu
Y
Li
Arundutt
A
Silamkoti
Gundurao
G
Kolavi
Liyuan
L
Mou
Shelly
S
Gulati
Gillian M
GM
Air
Wayne J
WJ
Brouillette
D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D019817:Benzoic Acid / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D057927:Hydrophobic and Hydrophilic Interactions; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects; D053122:Influenza A Virus, H3N2 Subtype / Q000187:drug effects; D009980:Influenza A virus / Q000187:drug effects / Q000201:enzymology*; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011760:Pyrrolidinones / Q000737:chemistry*; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D011760:Pyrrolidinones; D019817:Benzoic Acid; D009439:Neuraminidase