- ARYLAMIDINE DERIVATIVE, SALT THEREOF AND ANTIFUNGAL CONTAINING THESE
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An arylamidine derivative represented by the general formula (wherein R 1 represents optionally protected or substituted amidino; and R 2 and R 3 are the same or different and each represents hydrogen or halogeno) or a salt of the derivative. The derivati
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Page/Page column 26
(2008/06/13)
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- Studies on anti-MRSA parenteral cephalosporins II. Synthesis and antibacterial activity of 7 β-[2-(5-Amino-1,2,4-thiadiazol-3-yl)- 2(Z)-alkoxyiminoacetamido]-3(substituted imidazo[1,2-b] pyridazinium-1-yl)methyl-3-cephem-4-carboxylates and related compounds
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In an effort to discover a novel cefozopran (CZOP) derivative having excellent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), we performed chemical modification of the alkoxyimino moiety and imidazo[1,2-b]pyridazinium group of CZOP. Among the prepared compounds, the cyclopentyloxyimino derivative 7β-[2-(5- amino-1,2, 4-thiadiazol-3-yl)-2(Z) -cyclopentyloxyiminoacetamido] -3-(3,6-diaminoimidazo[1,2- b]pyridazinium-1-yl)methyl-3-cephem-4-carboxylate (20g) showed the most potent anti-MRSA activity, reflecting its high affinity (IC50=1.6μg/ml) for penicillin binding protein 2' (PBP2'), although its anti-MRSA activity was slightly inferior to that of vancomycin (VCM). In experimental systemic infection in mice, however, 20g showed activity comparable to that of VCM against MRSA. In addition, 20g showed activity similar or slightly inferior to that of CZOP against Pseudomonas aeruginosa both in vitro and in vivo. Considering its favorable antibacterial activity profile, 20g was considered to be the most promising CZOP derivative for further studies.
- Ishikawa,Kamiyama,Matsunaga,Tawada,Iizawa,Okonogi,Miyake
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p. 1071 - 1085
(2007/10/03)
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