Tebipenem Chemical Properties

Boiling point:

624.5±65.0 °C(Predicted)

Density 

1.75

storage temp. 

Sealed in dry,Store in freezer, under -20°C

solubility 

insoluble in EtOH; ≥19.15 mg/mL in H2O with gentle warming; ≥24.9 mg/mL in DMSO

form 

solid

pka

4.29±0.60(Predicted)

color 

White to khaki

Tebipenem Usage And Synthesis

Uses

Tebipenem is an orally available carbapenem antibiotic, shows broad-spectrum activity against Gram-positive and -negative bacteria, except for Pseudomonas aeruginosa.

Biological Activity

tebipenem is an orally available carbapenem antibiotic. tebipenem is active against a panel of clinical isolates from a variety of bacterial species (mic50s ≤ 0.0039 ~ 8 μg/ml), including methicillin-resistant strains of staphylococcus aureus (s. aureus) and staphylococcus epidermidis (s. epidermidis), as well as penicillin-resistant streptococcus pneumoniae (s. pneumonia). tebipenem also inhibits β-lactamase in a time- and concentration-dependent manner. tebipenem pivoxil, a derivative of tebipenem, has been under development as the first orally available carbapenem antibiotic for the treatment of respiratory and otolaryngological infections caused by drug-resistant s. pneumonia in pediatric patients.1. hazra s, xu h, blanchard js. tebipenem, a new carbapenem antibiotic, is a slow substrate that inhibits the β-lactamase from mycobacterium tuberculosis. biochemistry, 2014, 53(22): 3671-3678.2. fujimoto k, takemoto k, hatano k, et al. novel carbapenem antibiotics for parenteral and oral applications: in vitro and in vivo activities of 2-aryl carbapenems and their pharmacokinetics in laboratory animals. antimicrobial agents and chemotherapy, 2013, 57(2): 697-707.

Synthesis

The general procedure for the synthesis of (4R,5S,6S)-3-((1-(4,5-dihydrothiazol-2-yl)azetidin-3-yl)thio)-6-((R)-1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid from tepipenem condensate is as follows: to compound (II) (R is p-nitrobenzyl ) (15.0 g, 29.0 mmol) was added 200 mL of n-butanol and 200 mL of water and stirred until completely dissolved. Subsequently 8.00 g of Raney Ni was added and the hydrogenation reaction was carried out at 60 °C. The reaction was carried out at 2.0 MPa hydrogen pressure and 20 °C for 4 hours. Upon completion of the reaction, the solid was collected by filtration and the filter cake was washed with 15 mL of water. The filtrate was adjusted to pH 6.5 with 4-dimethylaminopyridine and then washed with 150 mL of ethyl acetate. After the solution was cooled to 0 °C, 700 mL of acetone was added drop by drop and stirred for 10 minutes, 700 mL of acetone was again added drop by drop and stirring was continued for 1 hour. Finally, 12.5 g of white solid tebutamidine was obtained with a yield of 94.5% and a purity of 99.6%.

IC 50

β-lactam

References

[1] Hazra S, et al. Tebipenem, a new carbapenem antibiotic, is a slow substrate that inhibits the β-lactamase from Mycobacterium tuberculosis. Biochemistry. 2014 Jun 10;53(22):3671-8 DOI:10.1021/bi500339j
[2] Seenama C, et al. In vitro activity of tebipenem against Burkholderia pseudomallei. Int J Antimicrob Agents. 2013 Oct;42(4):375. DOI:10.1016/j.ijantimicag.2013.06.016
[3] Li H, et al. In vitro antibacterial activities of two novel oral antibiotics, tebipenem and cefditoren, and other comparators against community-acquired respiratory tract infection-associated bacterial pathogens: A multicentre study in China. Int J Antimicrob Agents. 2014 Jan;43(1):92-3. DOI:10.1016/j.ijantimicag.2013.09.009

Tebipenem(161715-21-5)Related Product Information

• IBUTILIDE
• Lambrolizumab
• Cefpirome sulfate
• 2,2'-[Dithiobis(3,1-azetidinediyl)]bis[4,5-dihydrothiazole]
• RCIMVZWCHLOZJH-RRCSTGOVSA-N
• TEBIPENEM PIVOXIL