Novel antibacterial agents needed constantly to counter the ever emergent resistance development to commercially available drugs; one of the effective synthetic antibacterial classes is fluoroquinolone (FQ). This study includes structure activity relationship based design and synthesis of novel fluoroquinolone molecules active against resistant pathogens bearing mutations of DNA gyrase and/or topoisomerase IV which also express efflux pumps. Here, series of compounds were prepared by treating 1-cyclopropyl-6,7-difluoro-8-methoxy-1,4-dihydro-4-oxo-quinoline-3-carboxylic acid as a core with various 4-substituted-3,3-dialkyl piperidines as side chains, through conventional synthetic approaches. Subsequently, antibacterial activities of these fluoroquinolones were examined against Streptococcus pneumoniae, SPN 5844 (Moxi resistant DNA gyrase and topo IV mutant) and SPN 706 (FQ efflux positive). The current manuscript covers >50 examples of fluoroquinolone NCEs, amongst 20 NCEs have shown MIC in the range of (0.4 to >6.25 μg/ml) for SPN 5844 and (0.1–12.5 μg/ml) for SPN 706 strains. During the course of this study; WCK 919, comprising two chiral isomers; WCK 1152 and WCK 1153 were emerged as lead among the different series synthesized. Advance studies suggested either WCK 1152 or WCK 1153 are the worthy candidates for further clinical developments for respiratory infections caused by resistant pneumococci and staphylococci. However, on the basis of in house preclinical work, WCK 1152 had been selected for phase-1 domestic clinical trials.

不断需要新型抗菌剂来应对对市售药物不断出现的耐药性发展；一种有效的合成抗菌剂是氟喹诺酮（FQ）。该研究包括基于结构活性关系的新型氟喹诺酮分子的设计和合成，该分子对具有 DNA 旋转酶和/或拓扑异构酶 IV 突变的耐药病原体具有活性，这些病原体也表达外排泵。在这里，通过以1-环丙基-6,7-二氟-8-甲氧基-1,4-二氢-4-氧代-喹啉-3-羧酸为核心，以各种4-取代-3为核心，制备了一系列化合物， 3-二烷基哌啶作为侧链，通过常规合成方法。随后，检查了这些氟喹诺酮类药物对肺炎链球菌的抗菌活性，SPN 5844（莫西抗性 DNA 促旋酶和 topo IV 突变体）和SPN 706（FQ 流出阳性）。目前的手稿涵盖了超过 50 个氟喹诺酮 NCE 的例子，其中 20 个 NCE 显示SPN 5844的 MIC 范围为（0.4 至 >6.25 μg/ml ）， SPN 706菌株的 MIC 范围为（0.1-12.5 μg/ml） 。在本研究过程中；WCK 919，包含两种手性异构体；WCK 1152 和 WCK 1153 在合成的不同系列中作为先导出现。高级研究表明 WCK 1152 或 WCK 1153 是进一步临床开发由耐药性肺炎球菌和葡萄球菌引起的呼吸道感染的有价值的候选药物. 然而，在内部临床前工作的基础上，WCK 1152已入选国内1期临床试验。