29126-13-4Relevant academic research and scientific papers
FLUOROGENIC BETA-LACTAMASE SUBSTRATE AND ASSOCIATED DETECTION METHOD
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Page/Page column 40; 42-44, (2021/06/04)
This invention relates to probes for the detection of β-lactamase-type enzymatic activity. In particular, the invention relates to novel fluorogenic substrates for detecting the presence of a catalytically active β-lactamase and a detection method using such substrates.
Progress towards a stable cephalosporin-halogenated phenazine conjugate for antibacterial prodrug applications
Xiao, Tao,Liu, Ke,Huigens, Robert W.
supporting information, (2020/10/27)
Resistant bacteria successfully evade the action of conventional antibiotic therapies during infection, often leading to significant illness and death. Our lab has discovered halogenated phenazine (HP) analogues which demonstrate potent antibacterial activities through a unique iron-starving mechanism. Herein, we describe synthetic efforts towards a stable cephalosporin-HP conjugate prodrug with the aim of translating HPs into useful clinical agents. Cephalosporin-antibiotic conjugates offer multiple advantages for antibacterial design, including the release of active agents through the targeting of intracellular cephalosporinase following selective ring-opening of the beta-lactam warhead. During these studies, carbonate-linked cephalosporin-HP conjugate 16 was synthesized; however, we were unable to successfully remove the ester group required for cephalosporinase processing. Cephalosporin-HP 16 was then utilized as a probe to investigate the stability of the carbonate linker in antibacterial assays and, as predicted, this compound proved to be inactive against Staphylococcus aureus (MIC > 100 μM). The lack of 16’s antibacterial activity can be attributed to the carbonate linker remaining intact throughout the MIC assay, thus not liberating the active HP moiety. These efforts have led to a more stable cephalosporin-HP conjugate joined through a carbonate linker compared to a highly unstable ether linked analogue we previously reported.
Nitrocefin synthesis method
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, (2017/04/08)
The invention relates to a nitrocefin synthesis method and belongs to the field of drug synthesis. The invention provides a novel process for preparing nitrocefin from a compound I as a raw material. The compound I is prepared from 7-ACA. The nitrocefin synthesis method can realize synthesis of nitrocefin from 7-ACA as an initial raw material through seven processes. The 7-ACA as an initial raw material is a key intermediate of a cephalosporin, has already been industrialized and has a low market price. The nitrocefin synthesis method has the advantages of simple processes, easy reaction treatment, easy product purification, high yield, easy industrialization and low production cost.
Synthesis and total 1H- and 13C-NMR assignment of cephem derivatives for use in ADEPT approaches
Blau, Lorena,Menegon, Renato Farina,Ferreira, Elizabeth Igne,Ferreira, Antonio Gilberto,Boffo, Elisangela Fabiana,Tavares, Leila Aley,Heleno, Vladimir Constantino Gomes,Chung, Man-Chin
, p. 841 - 854 (2008/09/18)
We report the synthesis and total NMR characterization of 5-thia-1-azabicyclo-[4.2.0]oct-2-ene-2-carboxylic acid-3-[[[(4″- nitrophenoxy)carbonyl]oxy]-methyl]-8-oxo-7-[(2-thienyloxoacetyl)amino] -diphenylmethyl ester-5-dioxide (5), a new cephalosporin derivative. This compound can be used as the carrier of a wide range of drugs containing an amino group. The preparation of the intermediate product, 5-thia-1-azabicyclo[4.2.0] oct-2-ene-2-carboxylic acid-3-[methyl 4-(6-methoxyquinolin-8-ylamino) pentylcarbamate]-8-oxo-7-[(2-thienyloxoacetyl)amino]-diphenylmethyl ester-5-dioxide (6), as well as the synthesis of the antimalarial primaquine prodrug 5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid-3-[methyl 4-(6-methoxyquinolin-8-ylamino)pentylcarbamate]-8-oxo-7-[(2-thienyloxoacetyl) amino]- 5-dioxide (7) are also described, together with their total 1H- and 13C-NMR assignments.
Synthesis of beta-lactamase activated nitric oxide donors
Tang, Xiaoping,Cai, Tingwei,Wang, Peng George
, p. 1687 - 1690 (2007/10/03)
In order to achieve site specific delivery of NO, we designed conjugates of cephalosporin with NO donors. NO donors such as cupferron and SIN-1 were evaluated as potential choices for conjugates. Cephalosporin conjugated with SIN-1 demonstrated promising beta-lactamase dependent NO releasing ability.
Conjoint molecules of cephalosporins and aminoglycosides
Grapsas, Ioannis,Lerner, Stephen A.,Mobashery, Shahriar
, p. 295 - 301 (2007/10/03)
A general synthetic route to conjoint molecules of cephalosporins and aminoglycosides is described. These molecules were designed as potential substrates for bacterial β-lactamases, enzymes that hydrolyze the β-lactam bond of cephalosporins. Hydrolysis of the β-lactam bond was expected to release the C10-appended aminoglycoside. Since β-lactamases are sequestered in the periplasmic space of gram-negative bacteria, this sequence of events would liberate aminoglycoside inside such bacteria. It is expected that such local delivery of aminoglycosides would circumvent the inherent toxicity of aminoglycosides that occurs during systemic exposure within the mammalian host.
Extraction of N-blocked amino acids from aqueous media
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, (2008/06/13)
N-blocked amino acids, particularly derived from natural sources such as fermentation liquors, are extractively esterified from aqueous media by treatment of the aqueous solution with a diazoalkane, e.g. diphenyldiazomethane, in the presence of a water-im
