title: CP0569, a new broad-spectrum injectable carbapenem. Part 1: synthesis and structure-activity relationships.
abstract: A series of 1beta-methylcarbapenems bearing an (imidazo[5,1-b]thiazolium-6-yl)methyl moiety, a 5,5-fused heterobicycle, at the C-2 position was synthesized and evaluated for in vitro antibacterial activities. CP0569 (1r) and its analogues showed potent antibacterial activities against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), and Gram-negative bacteria, including Pseudomonas aeruginosa. Moreover, CP0569 (1r) exhibited stronger antibacterial activity against MRSA and higher resistance to renal dehydropeptidase-1 (DHP-1) than any currently marketed carbapenems, that is, imipenem (IPM), panipenem (PAPM), and meropenem (MEPM).
authors.affiliation: Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., 760Morooka-cho, Kohoku-ku, 222-8567, Yokohama, Japan. kazuhiro_aihara@meiji.co.jp
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Aihara
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kano
authors.forename: Sohjiro
authors.initials: S
authors.lastname: Shiokawa
authors.forename: Toshiro
authors.initials: T
authors.lastname: Sasaki
authors.forename: Fumihito
authors.initials: F
authors.lastname: Setsu
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Sambongi
authors.forename: Miyuki
authors.initials: M
authors.lastname: Ishii
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Tohyama
authors.forename: Takashi
authors.initials: T
authors.lastname: Ida
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tamura
authors.forename: Kunio
authors.initials: K
authors.lastname: Atsumi
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Iwamatsu
mesh_terms: D000818:Animals; D015780:Carbapenems / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004150:Dipeptidases / Q000378:metabolism; D024881:Drug Resistance, Bacterial; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D007769:Lactams / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016106:Methicillin Resistance; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013552:Swine
chemical_list: C483140:CP0569; D015780:Carbapenems; D007769:Lactams; D004150:Dipeptidases; C038937:dipeptidase