title: MexAB-OprM specific efflux pump inhibitors in Pseudomonas aeruginosa. Part 5: Carbon-substituted analogues at the C-2 position.
abstract: A series of 4-oxo-4H-pyrido[1,2-a]pyrimidine derivatives, derivatized at the 2-position with carbon-linked substituents, were synthesized and evaluated for their ability to potentiate the activity of the fluoroquinolone levofloxacin (LVFX) and the anti-pseudomonas beta-lactam aztreonam (AZT) in Pseudomonas aeruginosa. Palladium-catalyzed cross-coupling methods were applied for the incorporation of aliphatic and aromatic substituents.
authors.affiliation: Medicinal Chemistry Research Laboratory, Daiichi Pharmaceutical Co., Ltd, 16-13, Kita-Kasai 1-Chome, Tokyo 134-8630, Japan. yoshil1v@daiichipharm.co.jp
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Yoshida
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Nakayama
authors.forename: Noriko
authors.initials: N
authors.lastname: Kuru
authors.forename: Shozo
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Masami
authors.initials: M
authors.lastname: Ohtsuka
authors.forename: Makoto
authors.initials: M
authors.lastname: Takemura
authors.forename: Kazuki
authors.initials: K
authors.lastname: Hoshino
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kanda
authors.forename: Jason Z
authors.initials: JZ
authors.lastname: Zhang
authors.forename: Ving J
authors.initials: VJ
authors.lastname: Lee
authors.forename: William J
authors.initials: WJ
authors.lastname: Watkins
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001425:Bacterial Outer Membrane Proteins / Q000037:antagonists & inhibitors*; D002244:Carbon / Q000737:chemistry* / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D020128:Inhibitory Concentration 50; D026901:Membrane Transport Proteins; D008826:Microbial Sensitivity Tests; D008956:Models, Chemical; D011550:Pseudomonas aeruginosa / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D026901:Membrane Transport Proteins; C118598:MexA protein, Pseudomonas aeruginosa; C118597:MexB protein, Pseudomonas aeruginosa; D002244:Carbon