title: Potent oxazolidinone antibacterials with heteroaromatic C-ring substructure.
abstract: Novel oxazolidinone analogues bearing a condensed heteroaromatic ring as the C-ring substructure were synthesized as candidate antibacterial agents. Analogues 16 and 21 bearing imidazo[1,2-a]pyridine and 18 and 23 bearing [1,2,4]triazolo[1,5-a]pyridine as the C-ring had excellent in vitro antibacterial activities against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecalis (VRE), and penicillin-resistant Streptococcus pneumoniae (PRSP). They also showed promising therapeutic effects in a mouse model of lethal infection. Preliminary safety data (inhibitory effects on cytochrome P450 isoforms and monoamine oxidases) were satisfactory. Further evaluation of 18 and 23 is ongoing.
authors.affiliation: Research Foundation Itsuu Laboratory, 2-28-10 Tamagawa, Setagaya-ku, Tokyo 158-0094, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Research Foundation Itsuu Laboratory, 2-28-10 Tamagawa, Setagaya-ku, Tokyo 158-0094, Japan.
authors.forename: Iwao
authors.initials: I
authors.lastname: Utsunomiya
authors.affiliation: Research Foundation Itsuu Laboratory, 2-28-10 Tamagawa, Setagaya-ku, Tokyo 158-0094, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Shudo
authors.affiliation: Medicinal Research Laboratories, Shionogi & Co., Ltd , 1-1 Futaba-cho 3-chome, Toyonaka, Osaka 561-0825, Japan.
authors.forename: Takaji
authors.initials: T
authors.lastname: Fujimura
authors.affiliation: Medicinal Research Laboratories, Shionogi & Co., Ltd , 1-1 Futaba-cho 3-chome, Toyonaka, Osaka 561-0825, Japan.
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Tsuji
authors.affiliation: Medicinal Research Laboratories, Shionogi & Co., Ltd , 1-1 Futaba-cho 3-chome, Toyonaka, Osaka 561-0825, Japan.
authors.forename: Issei
authors.initials: I
authors.lastname: Kato
authors.affiliation: Medicinal Research Laboratories, Shionogi & Co., Ltd , 1-1 Futaba-cho 3-chome, Toyonaka, Osaka 561-0825, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Aoki
authors.affiliation: Medicinal Research Laboratories, Shionogi & Co., Ltd , 1-1 Futaba-cho 3-chome, Toyonaka, Osaka 561-0825, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Ino
authors.affiliation: Medicinal Research Laboratories, Shionogi & Co., Ltd , 1-1 Futaba-cho 3-chome, Toyonaka, Osaka 561-0825, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Iwaki
keywords: Antibacterial; condensed heteroaromatic ring; methicillin-resistant Staphylococcus aureus; oxazolidinone