Phillips Oludotun A, Sharaf Leyla H
a Department of Pharmaceutical Chemistry, Faculty of Pharmacy , Kuwait University , Safat , Kuwait.
Expert Opin Ther Pat. 2016 May;26(5):591-605. doi: 10.1517/13543776.2016.1168807. Epub 2016 Apr 4.
Antimicrobial resistance in Gram-positive bacteria is a major health care issue. This review summarizes patent publications from 2012 to 2015 that divulged novel oxazolidinones as antibacterial agents.
A total of 25 patents obtained from Espacenet, WIPO Patentscope and FreePatentsOnline, and AcclaimIP search engines were reviewed. The patents were scrutinized based on the novelty of the compounds, their antibacterial activity (MIC, µg/mL), and the process of preparation. The oxazolidinones with promising antibacterial activity were classified according to the following structural diversities, as biaryl heterocyclic, fused heteroaryl rings containing oxazolidinones, and others. The biaryl heterocyclic, fused heteroaryl, benzoxazine, and the 1H-pyrazol-1-yl containing oxazolidinone derivatives demonstrated potent antibacterial activities superior to linezolid against Gram-positive bacteria. Some derivatives were effective against standard strains of Gram-negative bacteria, namely Moraxella catarrhalis ATCC A894, and Escherichia coli ATCC 25922. In addition, a patent disclosed a structural isomer of linezolid with marginal activity against the aerobic Gram-negative bacteria MDR Stenotrophomonas (Xanthomonas) maltophilia, while linezolid and vancomycin did not inhibit growth. Finally, some derivatives showed activity against respiratory infectious diseases' causative agents, such as B. anthracis, B. mallei, Y. pestis, and M. pneumoniae.
Overall, there is limited in vivo data to support the potential clinical advancement of the currently reported novel derivatives.
革兰氏阳性菌中的抗菌药物耐药性是一个重大的医疗保健问题。本综述总结了2012年至2015年公布新型恶唑烷酮类抗菌剂的专利出版物。
共审查了从欧洲专利局专利数据库、世界知识产权组织专利数据库、免费专利在线数据库以及AcclaimIP搜索引擎获得的25项专利。根据化合物的新颖性、抗菌活性（最低抑菌浓度，μg/mL）和制备工艺对这些专利进行了审查。具有良好抗菌活性的恶唑烷酮类化合物根据以下结构多样性进行分类，即联芳基杂环、含恶唑烷酮的稠合杂芳环以及其他类型。联芳基杂环、稠合杂芳基、苯并恶嗪以及含1H-吡唑-1-基的恶唑烷酮衍生物对革兰氏阳性菌显示出优于利奈唑胺的强效抗菌活性。一些衍生物对革兰氏阴性菌的标准菌株，即卡他莫拉菌ATCC A894和大肠杆菌ATCC 25922有效。此外，一项专利公开了一种利奈唑胺的结构异构体，其对需氧革兰氏阴性菌多重耐药嗜麦芽窄食单胞菌（嗜麦芽寡养单胞菌）具有微弱活性，而利奈唑胺和万古霉素则无抑菌作用。最后，一些衍生物对呼吸道传染病的病原体，如炭疽芽孢杆菌、鼻疽芽孢杆菌、鼠疫耶尔森菌和肺炎支原体具有活性。
总体而言，支持目前报道的新型衍生物潜在临床进展的体内数据有限。
