Spiro-naphthyridinone piperidines as inhibitors of S. aureus and E. coli enoyl-ACP reductase (FabI).
Spiropiperidine naphthyridinone inhibitors of Staphylococcus aureus and Escherichia coli FabI have been prepared. Compounds 14a and 14c were identified as having sub-nanomolar E. coli FabI activity and are among the most potent FabI inhibitors yet described. The structural model of 14a bound to E. coli FabI is shown.
Sampson
Peter B
PB
Affinium Pharmaceuticals Inc. 1243 Islington Ave., Suite 600, Toronto, Ontario, Canada M8X 1Y9. psampson@uhnresearch.ca
Picard
Christine
C
Handerson
Sean
S
McGrath
Teresa E
TE
Domagala
Megan
M
Leeson
Andrew
A
Romanov
Vladimir
V
Awrey
Donald E
DE
Thambipillai
Dhushy
D
Bardouniotis
Elias
E
Kaplan
Nachum
N
Berman
Judd M
JM
Pauls
Henry W
HW
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D020134:Catalytic Domain; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology*; D008958:Models, Molecular; D009287:Naphthyridines / Q000737:chemistry / Q000494:pharmacology*; D010880:Piperidines / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D013141:Spiro Compounds / Q000737:chemistry / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000201:enzymology*; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D009287:Naphthyridines; D010880:Piperidines; D013141:Spiro Compounds; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)