TAK-599, a novel N-phosphono type prodrug of anti-MRSA cephalosporin T-91825: synthesis, physicochemical and pharmacological properties

T Ishikawa, N Matsunaga, H Tawada, N Kuroda…

Index: Ishikawa, Tomoyasu; Matsunaga, Nobuyuki; Tawada, Hiroyuki; Kuroda, Noritaka; Nakayama, Yutaka; Ishibashi, Yukio; Tomimoto, Mitsumi; Ikeda, Yukihiro; Tagawa, Yoshihiko; Iizawa, Yuji; Okonogi, Kenji; Hashiguchi, Shohei; Miyake, Akio Bioorganic and Medicinal Chemistry, 2003 , vol. 11, # 11 p. 2427 - 2437

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Citation Number: 108

Abstract

Crystalline 1 (TAK-599) is a novel N-phosphono prodrug of anti-methicillin-resistant Staphylococcus aureus (MRSA) cephalosporin 2a (T-91825) that has high affinity for penicillin-binding protein (PBP) 2′(IC50; 0.90 μg/mL) and shows potent in vitro anti-MRSA activity (MIC against MRSA N133; 1.56 μg/mL), comparable to that of vancomycin (1.56 μg/mL). Although 2a had insufficient water solubility (2.3 mg/mL) for parenteral ...