期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 54, 期 11, 页码 3704-3731出版社
AMER CHEMICAL SOC
DOI: 10.1021/jm1015395
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Employing a highly efficient total synthesis approach, we synthesized and evaluated for antibacterial activity diverse and novel pentacycline analogs with systematic variations at C7, C8, C9, and C10. Certain substitution groups, as well as substitution patterns at various positions, were found to be preferred for increased antibacterial activity. A number of pentacycline analogs displayed potent activity in vitro and in vivo, especially against Gram-positive organisms. Several analogs have also shown promising oral bioavailability in rats and cynomolgus monkey.
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