Structure and absolute configuration of thienamycin

Albers‐Schoenberg, G.; Arison, Byron H.; Hensens, Otto D.; Hirshfield, J.; Hoogsteen, Karst; Kaczka, Edward A.; Rhodes, Ryan E.; Kahan, J. S.; Kahan, Frederick M.

doi:10.1021/ja00488a038

Cited by 290 publications

(71 citation statements)

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“…no. 231) showed it to have at least equal and often superior in vitro and in vivo activity relative to thienamycin (1,4,5). The present study was undertaken to investigate the activity ofthis new compound against a variety of bacterial strains and to compare it with cefoxitin, cefazolin, carbenicillin, and axnikacin, all of which are in current clinical use.…”

mentioning

confidence: 98%

Antibacterial activities of a new stabilized thienamycin, N-formimidoyl thienamycin, in comparison with other antibiotics

Kesado¹,

Hashizume²,

Asahi³

1980

Antimicrob Agents Chemother

102

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The in vitro activity of a new crystalline derivative of thienamycin, N-formimidoyl thienamycin (MK0787), was tested against 46 laboratory reference strains and 2,158 clinical isolates of gram-positive and -negative bacteria, including anaerobes, and compared with cefoxitin, cefazolin, carbenicillin, and amikacin. MK0787 was significantly more active than the reference antibiotics against most bacteria tested. MK0787 was 16-to 500-fold more active than the other antibiotics against Staphylococcus aureus, Streptococcus pneumoniae, and group A and group B streptococci, inhibiting most isolates at concentrations less than 0.031 ,ug/ml. The inhibition concentration against over 90% of 156 strains of Streptococcus faecalis was 1 yg/ml. MK0787 had slightly less activity than carbenicillin against Haemophilus influenzae. The minimal inhibitory concentrations of MK0787 against strains of Enterobacter spp., Citrobacter spp., Serratia marcescens, Pseudomonas aeruginosa, and Clostridium difficile that are resistant to currently available antibiotics were less than or equal to 4 ,ug/ml. The only species found resistant to MK0787 was Pseudomonas maltophilia, which was equally nonsusceptible to the other reference antibiotics.N-Formimidoyl thienamycin (MK0787) The strains of Neisseria gonorrhoeae were grown on chocolate agar plates, and colonies were suspended in Trypto-soy broth just before dilution.Mueller-Hinton agar (BBL Microbiology Systems) was used for susceptibility determinations unless otherwise specified. This medium supplemented with 5% sheep blood and Brucella agar (BBL Microbiology Systems) supplemented with 5% sheep blood and 10 ug of hemin per ml were used for determining the susceptibilities of streptococci and anaerobes, respectively. Chocolate Mueller-Hinton agar was used for H. influenzae and N. gonorrhoeae. An inoculum prepared by dilution of a fresh overnight broth culture was placed on susceptibility testing plates with a 27-prong metal replicater (Microplanter, Sakuma Seisakusho, Ltd.) of which each inoculation prong was 912 on May 11, 2018 by guest http://aac.asm.org/ Downloaded from

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mentioning

confidence: 98%

Antibacterial activities of a new stabilized thienamycin, N-formimidoyl thienamycin, in comparison with other antibiotics

Kesado¹,

Hashizume²,

Asahi³

1980

Antimicrob Agents Chemother

102

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“…(This report was presented at the 19th Interscience Conference on Antimicrobial Agents and Chemotherapy, Boston, Mass., [1][2][3][4][5] October,…”

mentioning

confidence: 99%

MK0787 (N-formimidoyl thienamycin): evaluation of in vitro and in vivo activities

Kropp¹,

Sundelof²,

Kahan³

et al. 1980

Antimicrob Agents Chemother

196

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The practical application of thienamycin, a novel ,8-lactam antibiotic with a broad activity spectrum, was compromised by problems of instability. MK0787, N-formimidoyl thienamycin, does not have this liability. As reported, bacterial species resistant to most ,8-lactam antibiotics, such as Pseudomonas aeurginosa, Serratia, Enterobacter, Enterococcus, and Bacteroides spp., are uniformly susceptible to MK0787, usually at one-half the inhibitory level of thienamycin. Bactericidal ativityusuallv occurs at the minimal inhibitory concentration endpornt. Activity was reduced ony at the highest mocuum densities tested and by a lessor factor than was observed with reference 8l-lactam antibiotics active against P. aeruginosa and ,f-lactamase-bearing strains. MK0787 exhibits a broad spectrum of in vivo actvity when evaluated parenterally for efficacy against systemic infections in mice. The order of potency in vivo, 0.03 to 0.06 mg/kg for gram-positive species and 0.65 to 3.8 mg/kg for gram-negative infections including Pseudomonas, exceeded that of thienamycin and was at least 10-fold superior to reference ,B-lactam antibiotics including two recently developed agents with antipseudomonal activity, cefotaxime and LY127935.Thienamycin, a novel ,B-lactam antibiotic (1) (Fig. 1A)

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“…348 (5) A is substantially shorter than the value expected for a single bond. In contrast to these results, the fused-ring fl-lactam systems found in the penicillins and cephalosporins usually, but not always, exhibit substantial deviations of the ring N atom from its coordination plane and a concomitant nonplanarity of the four-membered ring (Sweet, 1972, and references therein; Applegate, Dolfini, Puar, Slusarchyk, Toeplitz & Gougoutas, 1974;Albers-Sch6nberg et al, 1978).…”

Section: Distances and Angles Within The Four-membered Ring Of Five Smentioning

confidence: 97%

3-Chloro-3-cyano-1-cyclohexyl-4-(phenylthio)-2-azetidinone. A substituted monocyclic β-lactam

Chambers¹,

Doedens²

1980

Acta Crystallogr Sect B

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Structure and absolute configuration of thienamycin

Cited by 290 publications

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Antibacterial activities of a new stabilized thienamycin, N-formimidoyl thienamycin, in comparison with other antibiotics

Antibacterial activities of a new stabilized thienamycin, N-formimidoyl thienamycin, in comparison with other antibiotics

MK0787 (N-formimidoyl thienamycin): evaluation of in vitro and in vivo activities

3-Chloro-3-cyano-1-cyclohexyl-4-(phenylthio)-2-azetidinone. A substituted monocyclic β-lactam

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