79660-46-1Relevant academic research and scientific papers
Fluorine walk: The impact of fluorine in quinolone amides on their activity against African sleeping sickness
Berninger, Michael,Erk, Christine,Fu?, Antje,Skaf, Joseph,Al-Momani, Ehab,Israel, Ina,Raschig, Martina,Güntzel, Paul,Samnick, Samuel,Holzgrabe, Ulrike
supporting information, p. 377 - 391 (2018/05/22)
Human African Trypanosomiasis, also known as African sleeping sickness, is caused by the parasitic protozoa of the genus Trypanosoma. If there is no pharmacological intervention, the parasites can cross the blood-brain barrier (BBB), inevitably leading to death of the patients. Previous investigation identified the quinolone amide GHQ168 as a promising lead compound having a nanomolar activity against T. b. brucei. Here, the role of a fluorine substitution at different positions was investigated in regard to toxicity, pharmacokinetics, and antitrypanosomal activity. This ‘fluorine walk’ led to new compounds with improved metabolic stability and consistent activity against T. b. brucei. The ability of the new quinolone amides to cross the BBB was confirmed using an 18F-labelled quinolone amide derivative by means of ex vivo autoradiography of a murine brain.
An efficient reduction of azide to amine: A new methodology to synthesize ethyl 7-amino-1-ethyl-6,8-difluoroquinolone-3-carboxylate and its spectroscopic characterization
Leyva-Ramos, Socorro,Hernández-López, Hiram,Jiménez-Cata?o, Rogelio,Chacón-García, Luis,Vega-Rodríguez, Sarai
, p. 939 - 947 (2017/05/01)
Most of the quinolone antibacterial research has been focused on the functionality at C-7 position where the nature of substituents is responsible for antibacterial spectrum, potency, bioavailability, and side effects of the quinolones. Then, a 7-amino-fluoroquinolone could be the starting point of a wide variety of potentially useful compounds like tetracyclic and tricyclic quinolones or secondary amines with side chain derivatives. This attracted our attention to synthesize a 7-azide-fluoroquinolone, which could be converted to amine performing a photochemical reaction using CuI as catalyst. FT-IR and H1 NMR spectra of the final product, ethyl 7-amino-1-ethyl-6,8-difluoroquinolone-3-carboxylate, suggests the formation of dimers, a feature already observed in norfloxacin.
Novel Glycoconjugate of 8-Fluoro Norfloxacin Derivatives as Gentamicin-resistant Staphylococcus aureus Inhibitors: Synthesis and Molecular Modelling Studies
Azad, Chandra S.,Bhunia, Shome S.,Krishna, Atul,Shukla, Praveen K.,Saxena, Anil K.
, p. 440 - 446 (2015/02/19)
Antibiotic resistance has been the subject of interest in clinical practice due to high prevalence of antibiotic-resistant pathogenic organisms. In view of the prevalence of lesser resistance in antibiotics belonging to aminoglycoside class of compounds viz. Food and Drug Administration-approved gentamicin for the treatment of Staphylococcus infections, which also has instances of resistance in the clinical isolates of Staphylococcus aureus, a series of novel glycoconjugates of 8-fluoro norfloxacin analogues with high regio-selectivity by employing copper (I)-catalyzed 1, 3-dipolar cycloaddition of 1-O-propargyl monosaccharides has been synthesized and evaluated for the antibacterial activity against gentamicin resistance Staphylococcus aureus. Among these compounds, the compound 10g showed better antibacterial activity (MIC = 3.12 μg/ml) than gentamicin (Escherichia coli (12.5 μg/ml), Staphylococcus aureus (6.25 μg/ml) and Klebsiella pneumonia (6.25 μg/ml), including gentamicin resistant (>50 μg/ml) strain in vitro). The docking studies suggest DNA gyrase of Staphylococcus aureus as a probable target for the antibacterial action of compound 10g.
Photochemistry of some non zwitterionic fluoroquinolones
Dichiarante, Valentina,Pretali, Luca,Fasani, Elisa,Albini, Angelo
, p. 41 - 48 (2013/10/22)
Two non zwitterionic analogues of fluoroquinolone drugs, viz. 1-ethyl-7-piperidino-8-fluoroquinol-4- one-3-carboxylic acid and 1-ethyl-7-piperidino-6,8-difluoroquinol-4-one-3-carboxylic acids have been synthesized and their photochemistry has been investigated. Both compound undergo photoheterolysis of the C8 F bond generating a triplet cation that either inserts into the 1-alkyl chain or is trapped or reduced by external nucleophiles. The reaction is analogous to that observed with the corresponding (zwitterionic) 7-piperazino derivatives, but the quantum yield is ca five times lower. This supports the rationalization that in the latter case assistance to defluorination by the N+ H bond has a determining role.
Quinolone derivatives containing strained spirocycle as orally active glycogen synthase kinase 3β (GSK-3β) inhibitors for type 2 diabetics
Seto, Shigeki,Yumoto, Kazuhiko,Okada, Kyoko,Asahina, Yoshikazu,Iwane, Aya,Iwago, Maki,Terasawa, Reiko,Shreder, Kevin R.,Murakami, Koji,Kohno, Yasushi
, p. 1188 - 1200 (2012/03/26)
The design, synthesis, and evaluation of 6-6-7 tricyclic quinolones containing the strained spirocycle moiety aiming at the GSK-3β inhibitor were described. Among the synthesized compounds, 44, having a cyclobutane ring on a spirocycle, showed excellent GSK-3β inhibitory activity in both cell-free and cell-based assays (IC50 = 36 nM, EC50 = 3.2 μM, respectively). Additionally, 44 decreased the plasma glucose concentration dose-dependently after an oral glucose tolerance test in mice.
Synthesis and antibacterial evaluation of novel 8-fluoro Norfloxacin derivatives as potential probes for methicillin and vancomycin-resistant Staphylococcus aureus
Sunduru, Naresh,Gupta, Leena,Chauhan, Kuldeep,Mishra, Nripendra N.,Shukla, Praveen K.,Chauhan, Prem M.S.
experimental part, p. 1232 - 1244 (2011/04/22)
A series of novel 8-fluoro Norfloxacin derivatives and the hybrids of its piperazinyl derivatives incorporated with 1,3,5-triazine and pyrimidine were synthesized. All the above compounds were evaluated for their antibacterial activity against Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus and methicillin & vancomycin-resistant S. aureus. Among all, compounds having Morpholine, N-methyl/phenyl/benzyl/pyrimidinyl piperazines and n-butylamine substitution at C-7 position, have shown increased potency in comparison to norfloxacin and ciprofloxacin.
Synthesis and in vitro antimicrobial evaluation of novel fluoroquinolone derivatives
Srinivasan, Shanmugam,Beema Shafreen, Raja Mohmed,Nithyanand, Paramasivam,Manisankar, Paramasivam,Pandian, Shunmugiah Karutha
experimental part, p. 6101 - 6105 (2011/01/13)
A series of 1-ethyl-6,8-difluoro-4-oxo-7(4-aryl piperazin-1-yl) 1,4-dihydro-quinoline-3-carboxylic acid derivatives (6a-f) and 1-ethyl-6,8-difluoro-4-oxo-7(4-piperidin-1-yl) 1,4-dihydro-quinoline-3- carboxylic acid derivatives (7a-e) were synthesized and evaluated for antibacterial and antifungal activities. The antimicrobial activities of the compounds were assessed by the microbroth dilution technique. The compounds were also evaluated for antifungal activity against Candida albicans (ATCC 90028) and Cryptococcous neoformans (ATCC 14116) pathogens. The preliminary in vitro evaluation studies revealed that some of the compounds have promising antimicrobial activities.
Microwave-assisted simple synthesis of substituted 4-quinolone derivatives
Cao, Xin,You, Qi-Dong,Li, Zhi-Yu,Yang, Yan,Wang, Xiao-Jian
experimental part, p. 4375 - 4383 (2010/05/01)
A simple and efficient method was developed for the synthesis of 4-quinolone-3-carboxylic esters and 4-quinolone-3-carbonitriles under microwave (MW) activation using anilines and acrylates as materials. All reactions demonstrated the benefits of microwave reactions: convenient operation, short reaction time, and good yields.
Synthesis of new quinolone antibiotics utilizing azetidine derivatives obtained from 1-azabicyclo[1.1.0]butane
Ikee, Yoshifumi,Hashimoto, Kana,Kamino, Mai,Nakashima, Masaaki,Hayashi, Kazuhiko,Sano, Shigeki,Shiro, Motoo,Nagao, Yoshimitsu
, p. 346 - 356 (2008/12/22)
A series of 3-sulfenylazetidine derivatives 5a-f were synthesized via the ring-opening reactions of 1-azabicyclo[ 1.1.0]butane (ABB, 3) with thiols 4a-f in 50-92% yields. Treatment of ABB (3) with aromatic amines 9a-e and dibenzylamine (9f) in the presence of Mg(ClO4)2 afforded the corresponding 3-aminoazetidine derivatives 10a-f in 24-65% yields. N-Benzyl-3-bromoazetidine (13), which was obtained by the reaction of ABB (3) with benzyl bromide, gave 3-aliphatic amino-substituted azetidine derivatives 15a, b. Novel fluoroquinolones 7a-f, 11a-f, 16a, b and 25a-c were obtained by the introduction of these azetidine derivatives into the C7 position of a quinolone nucleus 6 and N1-heterocyclic quinolones 21a-c in 21-83% yields. Some of them exhibited a greater antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) in comparison with that of clinically used fluoroquinolone, levofloxacin (LVFX).
Thermochemical reaction of 7-azido-1-ethyl-6,8-difluoroquinolone-3-carboxylate with heterocyclic amines. An?expeditious synthesis of novel fluoroquinolone derivatives
Leyva, Socorro,Leyva, Elisa
, p. 2093 - 2097 (2007/10/03)
Novel 7-hydrazino-1-ethyl-6,8-difluoroquinolone-3-carboxylate derivatives are obtained by thermochemical reaction of 7-azido-1-ethyl-6,8-difluoroquinolone-3-carboxylate with heterocyclic amines. These new fluoroquinolone carboxylates could be used as precursors in the preparation of novel fluoroquinolone carboxylic acids. These latter compounds are known to have biological activity.
