title: Conformationally-restricted analogues of efflux pump inhibitors that potentiate the activity of levofloxacin in Pseudomonas aeruginosa.
abstract: Conformational restriction of the ornithine residue of the efflux pump inhibitor D-ornithine-D-homophenylalanine-3-aminoquinoline (MC-02,595, 2) furnished bioisosteric proline derivatives that were less toxic in vivo and as active as the lead in potentiating the activity of the fluoroquinolone levofloxacin via the inhibition of efflux pumps in Pseudomonas aeruginosa.
authors.affiliation: Essential Therapeutics, Inc, 850Maude Avenue, Mountain View, CA 94043, USA. thomas.renau@roche.com
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Renau
authors.forename: Roger
authors.initials: R
authors.lastname: Léger
authors.forename: Lubov
authors.initials: L
authors.lastname: Filonova
authors.forename: Eric M
authors.initials: EM
authors.lastname: Flamme
authors.forename: Michael
authors.initials: M
authors.lastname: Wang
authors.forename: Rose
authors.initials: R
authors.lastname: Yen
authors.forename: Deidre
authors.initials: D
authors.lastname: Madsen
authors.forename: David
authors.initials: D
authors.lastname: Griffith
authors.forename: Suzanne
authors.initials: S
authors.lastname: Chamberland
authors.forename: Michael N
authors.initials: MN
authors.lastname: Dudley
authors.forename: Ving J
authors.initials: VJ
authors.lastname: Lee
authors.forename: Olga
authors.initials: O
authors.lastname: Lomovskaya
authors.forename: William J
authors.initials: WJ
authors.lastname: Watkins
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Ohta
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Nakayama
authors.forename: Yohei
authors.initials: Y
authors.lastname: Ishida
mesh_terms: D000613:Aminobutyrates / Q000737:chemistry; D000634:Aminoquinolines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D001425:Bacterial Outer Membrane Proteins / Q000037:antagonists & inhibitors*; D004357:Drug Synergism; D007928:Lethal Dose 50; D064704:Levofloxacin; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins / Q000037:antagonists & inhibitors*; D051379:Mice; D015242:Ofloxacin / Q000494:pharmacology*; D009952:Ornithine / Q000737:chemistry; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000613:Aminobutyrates; D000634:Aminoquinolines; D000890:Anti-Infective Agents; D001425:Bacterial Outer Membrane Proteins; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins; D064704:Levofloxacin; C014328:2-amino-4-phenylbutyric acid; D015242:Ofloxacin; D009952:Ornithine