10378. Ceftaroline

Nomenclature

CAS number: 189345-04-8
4-[2-[[(6R,7R)-7-[[(2Z)-2-(5-Amino-1,2,4-thiadiazol-3-yl)-2-(ethoxyimino)acetyl]amino]-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]thio]-4-thiazolyl]-1-methylpyridinium inner salt; 7β-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2(Z)-ethoxyiminoacetamido]-3-[4-(1-methyl-4-pyridinio)-1,3-thiazol-2-yl]thio-3-cephem-4-carboxylate; T-91825.
C22H20N8O5S4; mol wt 604.70.
C 43.70%, H 3.33%, N 18.53%, O 13.23%, S 21.21%.

Description and references

Fourth generation cephalosporin; active form of the N-phosphono prodrug, ceftaroline fosamil. Prepn: H. Tawada, K. Okonogi, JP 9100283 (1997 to Takeda); of N-phosphono prodrug: T. Ishikawa et al., WO 9932497; eidem, US 6417175 (1999, 2002 both to Takeda). Synthesis and physiochemical properties: T. Ishikawa et al., Bioorg. Med. Chem. 11, 2427 (2003) DOI PubMed. Stability study: Y. Ikeda et al., Chem. Pharm. Bull. 56, 1406 (2008) DOI PubMed. Comparative antibacterial spectrum in vitro: Y. Iizawa et al., J. Infect. Chemother. 10, 146 (2004) DOI PubMed. Experimental pharmacokinetics and pharmacodynamics: D. Andes, W. A. Craig, Antimicrob. Agents Chemother. 50, 1376 (2006) DOI PubMed. Comparative in vivo activity in experimental methicillin resistant Staphylococcus aureus (MRSA) infection: C. Jacqueline et al., ibid. 51, 3397 (2007) DOI PubMed. Clinical comparison with standard therapy for complicated skin and skin structure infections: G. H. Talbot et al., ibid. 51, 3612 (2007) DOI PubMed. Comprehensive review: D. Parish, N. Scheinfeld, Curr. Opin. Investig. Drugs 9, 201-209 (2008) PubMed.

Chemical structure

Properties

Soly in water: 2.3 mg/ml.

Derivative

Ceftaroline fosamil.

Nomenclature

CAS number: 229016-73-3; 595568-96-0 (monoacetate)
4-[2-[[(6R,7R)-2-carboxy-7-[[(2Z)-2-(ethoxyimino)-2-[5-(phosphonoamino)-1,2,4-thiadiazol-3-yl]acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]thio]-4-thiazolyl]-1-methylpyridinium inner salt; PPI-0903; TAK-599.
C22H21N8O8PS4; mol wt 684.68.
C 38.59%, H 3.09%, N 16.37%, O 18.69%, P 4.52%, S 18.73%.

Properties

Amorphous solid. Cryst from aq acetic acid as the monoacetic acid solvate, mp 221-223° (dec). Soly in water at 25°: >100 mg/ml.

Therapeutic Category

Antibacterial.

Keywords

Antibacterial (Antibiotics); β-Lactams; Cephalosporins