Design, synthesis, and structural analysis of inhibitors of influenza neuraminidase containing a 2,3-disubstituted tetrahydrofuran-5-carboxylic acid core.
(+/-)-(2R,3R,5R)-[2-(1'-S-acetamido-3'-methyl)butyl-3-methoxycarbonyl]tetrahydrofuran-5-carboxylic acid (9) and (+/-)-(2R,3R,5R)-[2-(1'-S-acetamido-3'-methyl)butyl-3-(4'-imidazolyl)]tetrahydrofuran 5-carboxylic acid (14) were synthesized as inhibitors of influenza neuraminidase (NA). Both compounds 9 and 14 inhibit influenza NA A with an IC(50) of about 0.5 microM and NA B with an IC(50) of 1.0 microM.
Wang
Gary T
GT
Global Pharmaceutical Research & Development, Abbott Laboratories, Abbott Park, IL 60064, USA. gary.t.wang@abbott.com
Wang
Sheldon
S
Gentles
Robert
R
Sowin
Thomas
T
Maring
Clarence J
CJ
Kempf
Dale J
DJ
Kati
Warren M
WM
Stoll
Vincent
V
Stewart
Kent D
KD
Laver
Graeme
G
D002264:Carboxylic Acids / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D005663:Furans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular; D015394:Molecular Structure; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D009975:Orthomyxoviridae / Q000201:enzymology*
D002264:Carboxylic Acids; D004791:Enzyme Inhibitors; D005663:Furans; D009439:Neuraminidase