Katsuyoshi Iwamatsu

CP6679, a new injectable cephalosporin. Part1: Synthesis and structure–activity relationships

A series of cephalosporins bearing a 5,5-fused ring system, an (imidazo[5,1-b]thiazolium-6-yl)methyl group, at the C-3 position were synthesized and evaluated for in vitro antibacterial activities. CP6679 (1s) and its analogues showed potent antibacterial activities against gram-positive and gram-negative bacteria, including Pseudomonas aeruginosa. They were also highly active against methicillin-resistant Staphylococcus aureus (MRSA). CP6679 (1s) showed more potent antibacterial activity than ceftazidime (CAZ) or cefpirome (CPR) against Pseudomonas aeruginosa and MRSA.

Novel cephalosporin derivatives possessing a bicyclic heterocycle at the 3-Position. Part II: Synthesis and antibacterial activity of 3-(5-Methylthiazolo[4,5-c]pyridinium-2-yl)thiomethylcephalosporin derivatives and related compounds

A series of cephalosporin derivatives with a thiazolopyridinium group at the 3-position was synthesized and evaluated for antibacterial activity. Some of these cephalosporin derivatives having a (5-alkylthiazolo[4,5-c]pyridinium-2-yl)thiomethyl group at the 3-position showed strong activity against Gram-positive and Gram-negative bacteria, including Pseudomonas aeruginosa. Among them, 5a showed a good antibacterial spectrum in vitro, and also showed a similar or slightly superior activity to that of ceftazidime in vivo against P. aeruginosa.

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).

Synthesis of novel di- and tricationic carbapenems with potent anti-MRSA activity.

A new series of 1beta-methyl carbapenems possessing a 6,7-disubstituted imidazo[5,1-b]thiazol-2-yl group directly attached to the C-2 position of the carbapenem nucleus was prepared, and their activities against methicillin-resistant Staphylococcus aureus (MRSA) were evaluated. First, a benzyl moiety was introduced at the C-6 position of imidazo[5,1-b]thiazole attached to the carbapenem. These benzylated molecules showed potent anti-MRSA activity, but poor water solubility. In order to overcome this drawback, we designed and synthesized di- and tricationic carbapenems and finally discovered a novel carbapenem (15i), which exhibited excellent anti-MRSA activity and good water solubility.