In the present study, to synthesize quinolone-piperazine alkylated analogues, initially 3,4-difluoro nitro benzene is reduced to yield 3,4-difluorobenzenamine which is treated with diethyl ethoxymethyl enemalonate to yield diethyl 2-((3,4-difluorophenylamino) methylene) malonate. This has been further cyclized to produce ethyl 6,7-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate which is treated with iodoethane to produce ethyl 1-ethyl-6,7-diifluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate. This is hydrolyzed and subsequent nucleophilic substitution with piperazine at 7th position gives quinolone-piperazine derivative. This is alkylated to yield 1-ethyl-6-fluoro-7-(4-alkylpiperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid which is treated with ethanol to afford the desired ethyl 1-ethyl-6-fluoro-7-(4-hexylpiperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylate derivatives. Based on the antimicrobial activity studies, hexyl analog 8a exhibits potent antimicrobial activity against Staphylococcus aureus MTCC 96, Bacillus subtilis MTCC 121, Micrococcus luteus MTCC 2470 (MIC value 1.9µg/mL), with respect to other synthesized compounds and reference drug ciprofloxacin. 8b (heptyl analogue) and 8c (nonyl analogue) show significant activity with MIC value 3.9µg/mL. In the case of antifungal screening, 8a, 8b and 8c show significant antifungal activity against Candida albicans MTCC 3017with MIC value ranged from 3.9 to 7.8µg/mL. Compounds 8a (butyl) shows potent minimum bactericidal concentration activity with MIC value 3.9µg/mL against the tested strains.

中文翻译：

---

新型烷基化哌嗪基氟喹诺酮羧酸酯衍生物的合成及抗菌性能评价

在本研究中，要合成喹诺酮-哌嗪烷基化的类似物，首先将3,4-二氟硝基苯还原生成3,4-二氟苯胺，然后将其用乙氧基甲基烯丙二酸二乙酯处理以生成2-乙基（（3,4-二氟苯基氨基）二乙基亚甲基）丙二酸酯。将其进一步环化以产生6,7-二氟-4-氧代-1,4-二氢喹啉-3-羧酸乙酯，将其用碘乙烷处理以产生1-乙基-6,7-二氟-4-氧代乙基-1。 ，4-二氢喹啉-3-羧酸酯。将其水解，随后在第七位用哌嗪进行亲核取代，得到喹诺酮-哌嗪衍生物。将其烷基化，得到1-乙基-6-氟-7-（4-烷基哌嗪-1-基）-4-氧代-1,4-二氢喹啉-3-羧酸，将其用乙醇处理，得到所需的乙基1。 -乙基-6-氟-7-（4-己基哌嗪-1-基）-4-氧代-1，4-二氢喹啉-3-羧酸酯衍生物。根据抗菌活性研究，己基类似物相对于其他合成化合物和参考药物环丙沙星，图8a展示了对金黄色葡萄球菌MTCC 96，枯草芽孢杆菌MTCC 121，黄褐微球菌MTCC 2470（MIC值为1.9µg / mL）的有效抗菌活性。8b（庚基类似物）和8c（壬基类似物）显示出显着的活性，MIC值为3.9µg / mL。在抗真菌筛选的情况下，8a，8b和8c对白色念珠菌MTCC 3017表现出显着的抗真菌活性，MIC值为3.9至7.8µg / mL。化合物8a （丁基）显示出对测试菌株有效的最小杀菌浓度，MIC值为3.9µg / mL。