Chemical modification of sulfazecin. Synthesis of 4-(substituted methyl)-2-azetidinone-1-sulfonic acid derivatives

• Published in: Journal of antibiotics Vol. 38; no. 3; p. 346
• Main Authors: Sendai, M, Hashiguchi, S, Tomimoto, M, Kishimoto, S, Matsuo, T, Kondo, M, Ochiai, M
• Format: Journal Article
• Language: English
• Published: Japan 01-01-1985
• Subjects: Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - pharmacology; Bacteria - drug effects; Lactams; Monobactams; Structure-Activity Relationship
• ISSN: 0021-8820
• DOI: 10.7164/antibiotics.38.346

In expectation of improving the antibacterial activity of sulfazecin by chemical modification at the 3- and 4-positions, a number of 3-[2-(2-aminothiazol-4-yl)-(Z)-2-(substituted oxyimino)-acetamido]-4-(substituted methyl)-2-azetidinone-1-sulfonic acids were synthesized. Among various 4-substituents explored, the carbamoyloxymethyl group was found to provide a good effect to the antibacterial activity of these 2-azetidinone derivatives. An extensive study of structure-activity relationships led to selecting (3S,4S)-3-[2-(2-aminothiazol-4-yl)-(Z)-2-carboxymethoxyiminoace tamido]-4- carbamoyloxymethyl-2-azetidinone-1-sulfonic acid, AMA-1080 (Ro 17-2301), which has highly potent antibacterial activity against Gram-negative bacteria including Pseudomonas aeruginosa, for further biological and subsequent clinical evaluation.