Tucker J A, Allwine D A, Grega K C, Barbachyn M R, Klock J L, Adamski J L, Brickner S J, Hutchinson D K, Ford C W, Zurenko G E, Conradi R A, Burton P S, Jensen R M
Discovery Research, Pharmacia & Upjohn, 7000 Portage Road, Kalamazoo, Michigan 49001, USA.
J Med Chem. 1998 Sep 10;41(19):3727-35. doi: 10.1021/jm980274l.
Oxazolidinones are a novel class of synthetic antibacterial agents active against gram-positive organisms including methicillin-resistant Staphylococcus aureus as well as selected anaerobic organisms. Important representatives of this class include the morpholine derivative linezolid 2, which is currently in phase III clinical trials, and the piperazine derivative eperezolid 3. As part of an investigation of the structure-activity relationships of structurally related oxazolidinones, we have prepared and evaluated the antibacterial properties of a series of piperazinyl oxazolidinones in which the distal nitrogen of the piperazinyl ring is substituted with a six-membered heteroaromatic ring. Compounds having MIC values </= 2 microg/mL vs selected gram-positive pathogens were discovered among each of the pyridine, pyridazine, and pyrimidine structural classes. Among these the cyanopyridine 17, the pyridazines 25 and 26, and the pyrimidine 31 exhibited in vivo potency vs S. aureus comparable to that of linezolid.
恶唑烷酮类是一类新型合成抗菌剂，对包括耐甲氧西林金黄色葡萄球菌在内的革兰氏阳性菌以及某些厌氧菌具有活性。该类的重要代表包括目前正处于III期临床试验的吗啉衍生物利奈唑胺2以及哌嗪衍生物依哌唑胺3。作为对结构相关恶唑烷酮类构效关系研究的一部分，我们制备并评估了一系列哌嗪基恶唑烷酮的抗菌性能，其中哌嗪环的远端氮原子被一个六元杂芳环取代。在吡啶、哒嗪和嘧啶结构类别中均发现了对选定革兰氏阳性病原体的最低抑菌浓度（MIC）值≤2μg/mL的化合物。其中，氰基吡啶17、哒嗪25和26以及嘧啶31对金黄色葡萄球菌的体内效价与利奈唑胺相当。
