Combrink Keith D, Denton Daniel A, Harran Susan, Ma Zhenkun, Chapo Katrina, Yan Dalai, Bonventre Eric, Roche Eric D, Doyle Timothy B, Robertson Gregory T, Lynch Anthony S
Department of Chemistry, Cumbre Pharmaceuticals Inc., 1502 Viceroy Drive, Dallas, TX 75235, USA.
Bioorg Med Chem Lett. 2007 Jan 15;17(2):522-6. doi: 10.1016/j.bmcl.2006.10.016. Epub 2006 Oct 12.
A novel series of 3-morpholino rifamycins in which the C25 acetate group was replaced by a carbamate group were prepared and found to exhibit significantly improved antimicrobial activity than rifampin against Mycobacterium smegmatis. Further characterization of such compounds suggests that relatively large groups attached to the rifamycin core via a C25 carbamate linkage prevent inactivation via ribosylation of the C23 alcohol as catalyzed by the endogenous rifampin ADP-ribosyl transferase of M. smegmatis. SAR studies of the C25 carbamate rifamycin series against M. smegmatis and other bacteria are reported.
制备了一系列新型的3-吗啉基利福霉素，其中C25位的乙酸酯基团被氨基甲酸酯基团取代，发现其对耻垢分枝杆菌的抗菌活性比利福平有显著提高。对这类化合物的进一步表征表明，通过C25氨基甲酸酯键连接到利福霉素核心的相对较大的基团可防止耻垢分枝杆菌内源性利福平ADP-核糖基转移酶催化的C23醇核糖基化而导致的失活。报道了C25氨基甲酸酯利福霉素系列对耻垢分枝杆菌和其他细菌的构效关系研究。
