title: Spiro-naphthyridinone piperidines as inhibitors of S. aureus and E. coli enoyl-ACP reductase (FabI).
abstract: 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.
authors.affiliation: Affinium Pharmaceuticals Inc. 1243 Islington Ave., Suite 600, Toronto, Ontario, Canada M8X 1Y9. psampson@uhnresearch.ca
authors.forename: Peter B
authors.initials: PB
authors.lastname: Sampson
authors.forename: Christine
authors.initials: C
authors.lastname: Picard
authors.forename: Sean
authors.initials: S
authors.lastname: Handerson
authors.forename: Teresa E
authors.initials: TE
authors.lastname: McGrath
authors.forename: Megan
authors.initials: M
authors.lastname: Domagala
authors.forename: Andrew
authors.initials: A
authors.lastname: Leeson
authors.forename: Vladimir
authors.initials: V
authors.lastname: Romanov
authors.forename: Donald E
authors.initials: DE
authors.lastname: Awrey
authors.forename: Dhushy
authors.initials: D
authors.lastname: Thambipillai
authors.forename: Elias
authors.initials: E
authors.lastname: Bardouniotis
authors.forename: Nachum
authors.initials: N
authors.lastname: Kaplan
authors.forename: Judd M
authors.initials: JM
authors.lastname: Berman
authors.forename: Henry W
authors.initials: HW
authors.lastname: Pauls
mesh_terms: 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
chemical_list: D000900:Anti-Bacterial Agents; D009287:Naphthyridines; D010880:Piperidines; D013141:Spiro Compounds; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)