CP0569, a new broad-spectrum injectable carbapenem. Part 1: synthesis and structure-activity relationships.
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).
Aihara
Kazuhiro
K
Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., 760Morooka-cho, Kohoku-ku, 222-8567, Yokohama, Japan. kazuhiro_aihara@meiji.co.jp
Kano
Yuko
Y
Shiokawa
Sohjiro
S
Sasaki
Toshiro
T
Setsu
Fumihito
F
Sambongi
Yumiko
Y
Ishii
Miyuki
M
Tohyama
Kazuyo
K
Ida
Takashi
T
Tamura
Atsushi
A
Atsumi
Kunio
K
Iwamatsu
Katsuyoshi
K
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
C483140:CP0569; D015780:Carbapenems; D007769:Lactams; D004150:Dipeptidases; C038937:dipeptidase