400827-46-5

Usage

Uses

Used in Pharmaceutical Industry:
Ceftaroline fosamil anhydrous base is used as an active pharmaceutical ingredient for the development of antibiotics targeting a wide range of bacterial infections. Its application is primarily for the treatment of adults with acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP).
Used in Hospital Settings:
Ceftaroline fosamil anhydrous base is used as an intravenous antibacterial agent for the treatment of patients with severe bacterial infections, particularly those caused by MRSA strains, multidrug-resistant S. pneumonia, and common gram-negative organisms. Its use in hospitals helps in managing and controlling the spread of antibiotic-resistant bacteria.
Used in Research and Development:
Ceftaroline fosamil anhydrous base serves as a subject of interest for researchers and scientists working on new antibacterial agents and understanding the mechanisms of action against various bacterial pathogens. This research can lead to the development of more effective treatments and strategies against drug-resistant infections.
Brand Name:
Teflaro is the brand name under which ceftaroline fosamil anhydrous base is marketed and distributed for medical use.

Originator

Takeda (Japan)

Clinical Use

#N/A

Synthesis

Reports from Takeda describe a process preparation of ceftaroline fosamil in 100 g scale which relies upon the assembly and union of fragments 112 and 114. The synthesis of fragment 112 began from commercially available benzhydryl 7b-[(phenylacetyl)amino]-3-hydroxy-3-cephem-4- carboxylate (106). The hydroxyl group within cephem 106 was reacted with methanesulfonyl chloride to produce mesylate 107 in 94% yield. The condensation of mesylate 107 with 4-(pyridin- 4-yl)thiazole-2-thiol 108 under the base condition of sodium methoxide gave compound 109 in 78% yield. Pyridinium salt 110 arose in quantitative yield upon subjection of 109 to iodomethane. Sequential deprotections of the amino group with phosphorous pentachloride and ester group with concentrated HCl afforded the dihydrochloride salt 112 in good yield. Acyl halide fragment 114 was prepared from commercially available (Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-ethoxyiminoacetic acid (113) in 60% yield by dichlorophosphorylation of the amino group and concomitant acid chloride formation. Acid chloride 114 was then reacted with dihydrochloride salt 112 in the presence of sodium acetate to give N-phosphono cephem 115 in 77% yield. The crystallization of 115 in an aqueous acetic acid solution gave rise to the stable acetic acid solvate ceftaroline fosamil acetate (IX).

Metabolism

Ceftaroline fosamil (prodrug) is converted into the active ceftaroline in plasma by phosphatase enzymes. Hydrolysis of the beta-lactam ring of ceftaroline occurs to form the microbiologically inactive, open-ring metabolite, ceftaroline M-1.Ceftaroline is mainly eliminated by the kidneys. Renal clearance is approximately equal, or slightly lower than the glomerular filtration rate in the kidney, and in vitro transporter studies indicate that active secretion does not contribute to the renal elimination of ceftaroline.