MexAB-OprM specific efflux pump inhibitors in Pseudomonas aeruginosa. Part 4: Addressing the problem of poor stability due to photoisomerization of an acrylic acid …

…, Y Yokomizo, A Sakamoto, H Kawato, K Yoshida…

Index: Nakayama, Kiyoshi; Kuru, Noriko; Ohtsuka, Masami; Yokomizo, Yoshihiro; Sakamoto, Atsunobu; Kawato, Haruko; Yoshida, Ken-Ichi; Ohta, Toshiharu; Hoshino, Kazuki; Akimoto, Katsuya; Itoh, Junko; Ishida, Hiroko; Cho, Aesop; Palme, Monica H.; Zhang, Jason Z.; Lee, Ving J.; Watkins, William J. Bioorganic and Medicinal Chemistry Letters, 2004 , vol. 14, # 10 p. 2493 - 2497

Full Text: HTML

Citation Number: 37

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.