title: Synthesis and in-vitro antibacterial activity of 7-(3-aminopyrrolo[3,4-c]pyrazol-5(2H,4H,6H)-yl)-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid derivatives.
abstract: A series of novel 7-(3-aminopyrrolo[3,4-c]pyrazol-5(2H,4H,6H)-yl)-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid derivatives was designed, synthesized and characterized by (1)H-NMR, MS and HRMS. These fluoroquinolones were evaluated for their in-vitro antibacterial activity against representative Gram-positive and Gram-negative strains. Generally, all of the target compounds display rather weak potency against the tested Gram-negative strains, but most of them exhibit good potency in inhibiting the growth of S. aureus including methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis including methicillin-resistant S. epidermidis (MRSE) (MIC: 0.125-8 µg/mL). In particular, the compound 9g is 2 to 32 fold more potent than gemifloxacin (GM), moxifloxacin (MX), gatifloxacin (GT), and levofloxacin (LV) against S. pneumoniae 08-3, K. pneumoniae 09-23, and P. aeruginosa ATCC27853, 4 to 32 fold more potent than MX, GM, and LV against K. pneumoniae 09-21, and more active than or comparable to the four reference drugs against P. aeruginosa 09-32.
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Guo
authors.forename: Xiao-Guang
authors.initials: XG
authors.lastname: Bai
authors.forename: Yi-Liang
authors.initials: YL
authors.lastname: Li
authors.forename: Zhi-Jiao
authors.initials: ZJ
authors.lastname: An
authors.forename: Le-Xing
authors.initials: LX
authors.lastname: Xu
authors.forename: Li-you
authors.initials: LY
authors.lastname: Han
authors.forename: Ming-Liang
authors.initials: ML
authors.lastname: Liu
authors.forename: Hui-Yuan
authors.initials: HY
authors.lastname: Guo
authors.forename: Yu-Cheng
authors.initials: YC
authors.lastname: Wang
mesh_terms: D000900:Anti-Bacterial Agents / Q000032:analysis / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D024841:Fluoroquinolones / Q000032:analysis / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D013212:Staphylococcus epidermidis / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: C568422:7-(3-aminopyrrolo(3,4-c)pyrazol-5(2H,4H,6H)-yl)-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones