New Potent Antibacterial Oxazolidinone (MRX-I) with an Improved Class Safety Profile
New Potent Antibacterial Oxazolidinone (MRX-I) with an Improved Class Safety Profile
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DOI：
10.1021/jm401931e
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发表时间：
2014-06-12
影响因子：
7.3
通讯作者：
Yuan, Zhengyu Y.
中科院分区：
文献类型：
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作者：
Gordeev, Mikhail F.;Yuan, Zhengyu Y.
恶唑烷酮类化合物是一类重要的抗菌蛋白质合成抑制剂。骨髓抑制和单胺氧化酶抑制(MAOI)是限制此类唯一批准药物利奈唑胺治疗不良反应的关键独立原因。本注释描述了一种新的恶唑烷酮类药物(S)-5-((isoxazol-3-ylamino)methyl)-3-(2，3，5-trifluoro-4-(4-oxo-3，4-dihydropyridin-1(2H)-yl)phenyl)oxazolidin-2-one(MRX-I)，其特点是对革兰氏阳性病原体具有高活性，并显著降低了骨髓抑制和MAOI的可能性。本文综述了该新药的医学需求、药物化学原理、临床前数据和I期临床试验总结。
Oxazolidinones comprise an important class of antibacterial protein synthesis inhibitors. Myelosuppression and monoamine oxidase inhibition (MAOI) are key independent causes for limiting adverse effects in therapy with the sole approved drug of this class, linezolid. This annotation describes a novel oxazolidinone agent, (S)-5-((isoxazol-3-ylamino)methyl)-3-(2,3,5-trifluoro-4-(4-oxo-3,4-dihydropyridin-1(2H)-yl)phenyl)oxazolidin-2-one (MRX-I), distinguished by its high activity against Gram-positive pathogens coupled with markedly reduced potential for myelosuppression and MAOI. The medical need, medicinal chemistry rationale, preclinical data, and phase I clinical trial summary for this new agent are reviewed herein.