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本文在比较详细地介绍了6-位非氟喹诺酮(NFQs)的发现、发展及其代表物T-3811出现全过程的基础上,阐述了NFQs的结构优化策略,7-和8-位取代基对抗菌活性的影响等。构-效关系研究表明,6-氟代对抗菌活性的贡献大小主要取决于7-位取代基的性质,活性越强的NFQs6-位引入氟原子对其活性的贡献越小,从而为NFQs的进一步发展奠定了理论基础。本文还简要介绍了NFQs具有比氟喹诺酮(FQs)更小的基因毒性、更优良的体内活性、与靶酶相互作用以及更不易产生耐药性等特点。总之,具有优良抗菌活性的NFQs的出现,是对“6-氟代是使喹诺酮具有优良抗菌活性所必需”这一传统认识的重大突破,而目前已接近完成Ⅲ期临床研究的T-3811(garenoxacin)无疑更坚定了人们对NFQs进一步研究的信心。同时,随着对NFQs构-效关系认识的不断深入,今后必将会筛选出更具特点的NFQs类药物造福人类。
In this paper, we introduced the discovery, development of 6-position non-fluoroquinolones (NFQs) and the whole process of its representative T-3811 in detail. The structural optimization strategies of NFQs, 7- and 8- The impact of antibacterial activity and so on. The study of the structure-activity relationship shows that the contribution of the 6-fluoro to the antibacterial activity mainly depends on the nature of the substituent at the 7-position. The stronger the activity of the NFQs, the smaller the contribution of the introduced fluorine atom to its activity is, Further development has laid a theoretical foundation. This article also briefly describes the NFQs have less genotoxicity than FQs, better in vivo activity, interaction with the target enzyme and less susceptibility to drug resistance. In summary, the appearance of NFQs with excellent antibacterial activity is a major breakthrough in the traditional recognition that “6-fluoro is essential for the excellent antibacterial activity of quinolones”, and is currently nearing completion of phase III clinical studies of T-3811 ( garenoxacin) will undoubtedly strengthen people’s confidence in the further study of NFQs. At the same time, with the continuous understanding of the structure-activity relationship of NFQs, NFQs will be screened out more for the benefit of human beings in the future.