Synthesis and antibacterial activity of men 10700, a new penem antibiotic

Altamura, Maria Maddalena; Perrotta, Enzo; Sbraci, Piero; Pestellini, V.; Arcamone, Federico; Cascio, G; Satta, G.; Morandotti, Grazia Angela; Sperrung, Roberta

doi:10.1016/0960-894x(95)00072-2

Cited by 7 publications

(3 citation statements)

References 14 publications

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“…A trinem, sanfetrinem (GV 104326), has also been studied for its in vitro activity [7,8]. Men 10700 is a new alkylaminopenem with broad-spectrum antibacterial activity, encompassing most grampositive and gram-negative bacteria, with the exception of Pseudomonas aeruginosa [9][10][11][12]. It is more active than ritipenem against many species, especially Enterobacter spp.…”

Section: Introductionmentioning

confidence: 99%

In vitro Antibacterial Activity of Men 10700, a New Penem Antibiotic

et al. 1999

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We report here the antibacterial activity of the new penem antibiotic Men 10700 against a total of 740 gram-positive and gram-negative clinical isolates, in comparison to imipenem, meropenem, cefotaxime, ceftriaxone, ciprofloxacin and gentamicin. Men 10700 has shown a wide spectrum of antibacterial activity, with a potent activity both against gram-positive species (with the exception of methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis) as indicated by minimal inhibitory concentration (MIC₉₀) values ≤0.5 mg/l, and gram-negative species, with MIC₉₀ values generally ≤2 mg/l. Men 10700 was the most potent antibiotic against methicillin-susceptible S. aureus and S. epidermidis, while the overall spectrum of activity resembled that of imipenem; meropenem was more active against most gram-negative species. In comparison with third-generation cephalosporins, Men 10700 demonstrated superior activity against methicillin-susceptible S. aureus and S. epidermidis and some gram-negative species such as Morganella morganii, Serratia spp. and Enterobacter cloacae; moreover, in contrast to third-generation cephalosporins, Men 10700 showed moderate activity against Enterococcus spp. The activity of Men 10700 against penicillin-resistant Streptococcus pneumoniae (10 strains) and some gram-negative strains selected for their resistance to cefotaxime (20 strains) was particularly interesting.

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Section: Introductionmentioning

confidence: 99%

In vitro Antibacterial Activity of Men 10700, a New Penem Antibiotic

et al. 1999

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“…glycinamide), 5-methylthiazole 13 (R1 = R2 = R3 = R4 = H) was obtained20 (Scheme 3) as the sole product.22 Evidently, steric factors influence reaction outcome (Table 3); the use of a more hindered amide, such as leucinamide (entry 2) instead of glycinamide (entry 1), still allowed for recovery of some penem compound. However, nucleophilic substitution at C-2 became the prevalent reaction only with the use of iV-alkyl (entries [3][4][5][6][7][8][9][10][11][12] or cyclic (entries 13-21) amino acid derivatives, bearing in any case a secondary nucleophilic nitrogen. Different alkyl substitutions on the nitrogen atom or -substitutions on the amino acid slightly influenced the reaction outcome (compare entries 3 os 4, 1 vs 2, and 3 vs 9), as did insertion of a different moiety on the carboxy group (entries 3 vs 10 and 11 and 14 vs 17).…”

Section: Chemistrymentioning

confidence: 99%

2-Substituted Penems with Amino Acid-Related Side Chains: Synthesis and Antibacterial Activity of a New Series of .beta.-Lactam Antibiotics

Altamura

Perrotta²,

Sbraci³

et al. 1995

J. Med. Chem.

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A new series of 6-(hydroxyethyl)penems 2-substituted with amino acid-related side chains was synthesized. The nature of the amino acyl derivative proved to be crucial both from a synthetic point of view, as beta-lactam ring opening can compete with C-2 nucleophilic substitution, and for antibacterial activity. Primary amino acid amides emerged as the most suitable side chains for enhancing permeability through a Gram-negative outer membrane. In vitro activity of the new 2-[(aminoamido)methyl]penems 3a-u was influenced by the nature and position of the amide moiety, the ring size for cyclic amides, and the configuration of the amino acid. Compounds bearing amides derived from small N-methyl amino acids (such as 3a) or from cyclic amino acids (such as prolinamide 3p and 4-hydroxyprolinamide 3r) showed broad spectrum in vitro activity against both Gram-positive and Gram-negative microorganisms.

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“…1) [7,8] against clinical isolates. The compound is currently in preclinical development as a broad-spectrum antibacterial agent for parenteral administration and for oral administration as the prodrug form MEN 11505.…”

Section: Introductionmentioning

confidence: 99%

MEN 10700, a New Penem Antibiotic: In vitro Antibacterial Activity on Clinical Isolates

Ferrari

Altamura²,

Luca³

et al. 2002

Chemotherapy

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MEN 10700 is a new broad-spectrum penem, currently in preclinical development. In the present study, the activity of MEN 10700 was compared to that of imipenem, meropenem, cefotaxime, ampicillin/sulbactam, amikacin and ciprofloxacin against 619 gram-positive and gram-negative bacterial strains, and to that of imipenem, meropenem, cefotaxime, ceftriaxone, ceftazidime, cefepime and ampicillin/sulbactam against 38 strains of ciprofloxacin-resistant Escherichia coli, and against 19 extended-spectrum-β-lactamase (ESBL)-producing strains of the KES group. MEN 10700 was highly active against most gram-positive and gram-negative strains, and overall demonstrated comparable activity to imipenem and meropenem. Methicillin-susceptible Staphylococcus aureus and methicillin-susceptible Staphylococcus epidermidis were highly susceptible to MEN 10700, which was the most potent among the antibiotics tested. MEN 10700 was less potent than the carbapenem antibiotics on Morganella morganii, Serratia marcescens and Acinetobacter spp. Ciprofloxacin-resistant E. coli were uniformly susceptible to MEN 10700, imipenem and meropenem, with MIC₉₀ values in the range of ≤0.12–0.25 mg/l, while showing much lower susceptibility to the other antibiotics tested, including the fourth-generation cephalosporin cefepime. This feature was even more evident in ESBL-producing strains of the KES group, with an MIC₉₀ of 1– 2 mg/l for MEN 10700, imipenem and meropenem, and a MIC₉₀ of 16–64 mg/l for the other antibiotics tested, including cefepime.

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Synthesis and antibacterial activity of men 10700, a new penem antibiotic

Cited by 7 publications

References 14 publications

In vitro Antibacterial Activity of Men 10700, a New Penem Antibiotic

In vitro Antibacterial Activity of Men 10700, a New Penem Antibiotic

2-Substituted Penems with Amino Acid-Related Side Chains: Synthesis and Antibacterial Activity of a New Series of .beta.-Lactam Antibiotics

MEN 10700, a New Penem Antibiotic: In vitro Antibacterial Activity on Clinical Isolates

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