MexAB-OprM specific efflux pump inhibitors in Pseudomonas aeruginosa. Part 5: Carbon-substituted analogues at the C-2 position.
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.
Yoshida
Ken-ichi
K
Medicinal Chemistry Research Laboratory, Daiichi Pharmaceutical Co., Ltd, 16-13, Kita-Kasai 1-Chome, Tokyo 134-8630, Japan. yoshil1v@daiichipharm.co.jp
Nakayama
Kiyoshi
K
Kuru
Noriko
N
Kobayashi
Shozo
S
Ohtsuka
Masami
M
Takemura
Makoto
M
Hoshino
Kazuki
K
Kanda
Hiroko
H
Zhang
Jason Z
JZ
Lee
Ving J
VJ
Watkins
William J
WJ
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*
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