title: MexAB-OprM specific efflux pump inhibitors in Pseudomonas aeruginosa. Part 4: Addressing the problem of poor stability due to photoisomerization of an acrylic acid moiety.
abstract: Exchange of the ethylene tether in a series of pyridopyrimidine-based MexAB-OprM specific efflux pump inhibitors to an amide bond stabilized the olefin of the acrylic acid moiety, preventing facile photoisomerization to the Z-isomer. Furthermore, the activity was drastically improved in the amide tether variants, providing extremely potent acrylic acid and vinyl tetrazole analogues.
authors.affiliation: Daiichi Pharmaceutical Co., Ltd, 1-16-13, Kitakasai, Edogawa, Tokyo 134-8630, Japan. nakaygoi@daiichipharm.co.jp
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Nakayama
authors.forename: Noriko
authors.initials: N
authors.lastname: Kuru
authors.forename: Masami
authors.initials: M
authors.lastname: Ohtsuka
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yokomizo
authors.forename: Atsunobu
authors.initials: A
authors.lastname: Sakamoto
authors.forename: Haruko
authors.initials: H
authors.lastname: Kawato
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Yoshida
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Ohta
authors.forename: Kazuki
authors.initials: K
authors.lastname: Hoshino
authors.forename: Katsuya
authors.initials: K
authors.lastname: Akimoto
authors.forename: Junko
authors.initials: J
authors.lastname: Itoh
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ishida
authors.forename: Aesop
authors.initials: A
authors.lastname: Cho
authors.forename: Monica H
authors.initials: MH
authors.lastname: Palme
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: D000179:Acrylates / Q000494:pharmacology; D001425:Bacterial Outer Membrane Proteins / Q000037:antagonists & inhibitors*; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D004355:Drug Stability; D007536:Isomerism; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins / Q000037:antagonists & inhibitors*; D008826:Microbial Sensitivity Tests; D010777:Photochemistry; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000179:Acrylates; D001425:Bacterial Outer Membrane Proteins; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins; C118598:MexA protein, Pseudomonas aeruginosa; C118597:MexB protein, Pseudomonas aeruginosa; D011743:Pyrimidines; C036658:acrylic acid