Experimental evaluation of HR 756, a new cephalosporin derivative: Pre-clinical study

Heymes, R.; Lutz, A; Schrinner, E

doi:10.1007/bf01640793

Cited by 75 publications

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“…These latter organisms often have been resistant both to older cephalosporins and even to the new ones. Recently a cephalosporin, HR 756, 7-[2-(2-amino-4-thiazolyl)-2-(Z)-(methoximino)acetamido] cephalosporanic acid, has been reported to be active against Pseudomonas (5,6). We have shown that this agent is resistant to ,8-lactamases (5) and so have undertaken an extensive evaluation of this agent to compare its activity to other fi-lactam compounds, both penicillins and cephalosporins.…”

mentioning

confidence: 99%

HR 756, a New Cephalosporin Active Against Gram-Positive and Gram-Negative Aerobic and Anaerobic Bacteria

Neu

Aswapokee

et al. 1979

Antimicrob Agents Chemother

152

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The in vitro activity of HR 756, 7-[2-(2-amino-4-thiazolyl)-2-(Z)-(methoximino)acetamido] cephalosporanic acid, was investigated against 659 isolates. HR 756 inhibited Neisseria and Haemophilus species at concentrations similar to those needed with ampicillin. It inhibited β-lactamase-producing N. gonorrhoeae and H. influenzae . HR 756 was the most active compound tested against members of the Enterobacteriaceae , inhibiting most isolates of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Salmonella, Enterobacter , and Shigella at concentrations of less than 0.1 μg/ml. It was twice as active as carbenicillin against Pseudomonas aeruginosa and inhibited Bacteroides fragilis as well as cefoxitin. HR 756 killed E. coli, Staphylococcus aureus , and P. aeruginosa at rates similar to other β-lactam antibiotics.

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mentioning

confidence: 99%

HR 756, a New Cephalosporin Active Against Gram-Positive and Gram-Negative Aerobic and Anaerobic Bacteria

Neu

Aswapokee

et al. 1979

Antimicrob Agents Chemother

152

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“…Thus, S-alkylation of the previously reported 4-thiopyridones (4a~4c)8) ( Fig. 1) with the 3-chloromethyl cephalosporin (1) in the presence of sodium iodide proceeded in high yield to the corresponding ester (2), as a mixture of chloride and iodide salts. Subsequent TFA deprotection concomitantly removed all the protecting groups from (2), including any ter^-butoxycarbonyl groups on the 7V-aminopyridinium thiomethyl moiety, to provide the initial target derivatives (3a -3c).…”

Section: Chemistrymentioning

confidence: 63%

“…1,H 6.7,N 13.3. Found: C 57.4,H 6.9,N 13.4. l -[A^-(^rr-Butyloxycarbonyl)-Ar-(rerr-butyloxycarbonylmethyl)amino] -4-pyridone (7g) To compound (6) (0.2g, 0.95mmol) in DMF(10ml) was added successively potassium carbonate (0.143 g, 1.04mmol) and tert-buty\ bromoacetate (0.17ml, 1.04mmol).…”

Section: Methodsmentioning

confidence: 99%

Synthesis and biological properties of some 3-((N-subtstituted-amino)pyridinium-4-thiomethyl)-7-((2-amino-thiazol-4-yl)-2-(Z)-(methoxyimino)acetamido)ceph-3-em-4-carboxylates.

et al. 1993

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The synthesis and antibacterial activity of a series of /Mactamase stable, broad spectrum 7-[2-(2-amino-thiazol-4-yl)-2-(Z)-(methoxyimino)acetamido] -cephalosporins, characterised by a C-3-[Af-(substituted-amino)pyridinium-4-thiomethyl] group, is described.Gram-positive and Gramnegative bacteria including extended spectrum /?-lactamase-producing strains were most susceptible to the A^-amino-and iV-methylamino derivatives (3a) and (3b); with the exception of Pseudomonas aeruginosa, (3b) was more active in vitro and in vivo than cefpirome or ceftazidime.The development of the C-7 (2-aminothiazolyloxyimino)cephalosporins with their inherent good stability to /Mactamases has led to established antibacterial agents such as cefotaxime,1* ceftazidime2) and ceftriaxone3) and the newly marketed cefpirome.4) A primary concern in the search for new /Mactam antibiotics remains their stability to /Mactamases since these enzymes are still a major cause of treatment failure. The recent emergence of extended spectrum /Mactamase-producing bacteria has further highlighted the need for new potent broad spectrum agents with enhanced /Mactamasestability. Good activity against Gram-positive and Gram-negative bacteria including /Mactamase producing strains has been reported for 2-aminothiazolyloxyimino cephalosporins with a C-3[N-alkylpyridinium-4-thiomethyl]-or [J/V-alkylcyclopenteno[Z7]pyridinium-4-thiomethyl] group.5~7) Within these series, poor aqueous solubility and relatively high acute toxicity has been found for some derivatives lacking an additional carboxy group. Introduction of such an acidic moiety often improved solubility and toxicity but at the expense of someGram-positive potency. A recent report from these laboratories describes a series of 7a-formamido cephalosporins, characterised by a novel C-3 [A^-(substituted-amino)pyridinium-4-thiomethyl] group. 8) Although these compounds were highly /Mactamase stable agents with potent Gram-negative activity, including Pseudomonas aeruginosa, the Gram-positive activity was of borderline clinical utility. It was of interest therefore to investigate the effect of this particular C-3 substitution on the biological properties of conventional cephalosporins, where improved anti-staphylococcal potency might be anticipated. Our initial studies focused on 3-[(iV-substituted-amino)pyridinium-4-thiomethyl] -7-[2-(2-amino-thiazol-4-yl)-2-(Z)-(methoxyimino)acetamido] -ceph-3-em-4-carboxylates (3) which form the subject of this paper.Chemistry

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“…Ceftriaxone (Ro 13-9904), a 2-aminothiazolyl methoxyimino cephalosporin derivative, is one of several "thirdgeneration" cephalosporins developed in recent years. Included in this group are the currently marketed drugs cefotaxime (10) and moxalactam (13), as well as the investigational agents cefoperazone (16), ceftazidime (20), cefmenoxime *(28), and ceftizoxime (12). All possess excellent activity against many gram-positive and gramnegative bacteria, including a number of species not susceptible to earlier cephalosporins.…”

mentioning

confidence: 99%

Ceftriaxone: in vitro studies and clinical evaluation

Gnann¹,

Goetter²,

Elliott³

et al. 1982

Antimicrob Agents Chemother

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The in vitro activity of ceftriaxone against 437 clinical isolates of gram-negative bacilli was determined. Ceftriaxone was found to have high in vitro activity against Enterobacteriaceae, with the exception of Enterobacter cloacae. Ceftriaxone was only minimally active against Pseudomonas aeruginosa and Acinetobacter calcoaceticus. We evaluated the clinical efficacy and toxicity of ceftriaxone in 55 adult patients. Bacterial infection was confirmed by the isolation of etiological bacteria in 30 patients. Infectious disorders treated included 10 pneumonias, 13 urinary tract infections, and 7 soft tissue or bone infections. Pathogens identified were 25 isolates of gram-negative bacilli, 5 isolates of Staphylococcus aureus, 5 isolates of pneumococci, and 4 isolates of other streptococci. The overall efficacy of ceftriaxone was excellent. The clinical cure rate was 93%, and the bacteriological cure rate was 93%. A total of 30 adverse reactions were noted in 22 of 55 patients receiving ceftriaxone, but only one necessitated discontinuation of treatment. Adverse effects frequently noted were elevated hepatic enzymes (16%), thrombocytosis (16%), and eosinophilia (8%). Ceftriaxone is an effective and well-tolerated antimicrobial agent that appears promising for the treatment of serious gram-negative bacillary infections.

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Experimental evaluation of HR 756, a new cephalosporin derivative: Pre-clinical study

Cited by 75 publications

References 0 publications

HR 756, a New Cephalosporin Active Against Gram-Positive and Gram-Negative Aerobic and Anaerobic Bacteria

HR 756, a New Cephalosporin Active Against Gram-Positive and Gram-Negative Aerobic and Anaerobic Bacteria

Synthesis and biological properties of some 3-((N-subtstituted-amino)pyridinium-4-thiomethyl)-7-((2-amino-thiazol-4-yl)-2-(Z)-(methoxyimino)acetamido)ceph-3-em-4-carboxylates.

Ceftriaxone: in vitro studies and clinical evaluation

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