A novel prodrug of an impermeant inhibitor of 3-deoxy-D-manno-2-octulosonate cytidylyltransferase has antibacterial activity

DW Norbeck, W Rosenbrook, JB Kramer…

文献索引：Norbeck, Daniel W.; Rosenbrook, William; Kramer, James B.; Grampovnik, David J.; Lartey, Paul A. Journal of Medicinal Chemistry, 1989 , vol. 32, # 3 p. 625 - 629

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被引用次数: 17

摘要

Although 8-amino-2, 6-anhydro-3, 8-dideoxy-~-glycero-~-talo-octonic acid (2) is a potent inhibitor of 3-deoxy-~-manno-octulosonate cytidylyltransferase (CMP-KDO synthetase), it is unable to reach its cytoplasmic target and is therefore inactive as an antibacterial agent. However, esterification of 2 with 8-(hydroxymethyl)-l-naphthyl methyl disulfide (8) generates a prodrug (12), which gains entry into bacterial cells. Intracellular reduction of the disulfide ...