Cephalosporins

Abstract

CEPHALOSPORINSThe cephalosporins, a subgroup of β-lactam antibiotics, consist of a 4-membered lactam ring fused through the nitrogen and the adjacent tetrahedral carbon atom to a second heterocycle forming a 6-membered dihydrothiazine ring. Other structural features common to all the cephalosporins are a carboxyl group on the dihydrothiazine ring on the carbon next to the ring nitrogen and a functionalized amino group on C-7, the carbon of the β-lactam ring opposite the nitrogen. These features are evidenced in 7-aminocephalosporanic acid [957-68-6] (7-ACA), C 10 H 12 N 2 O 5 S 1. Cephalosporins, like all β-lactam antibiotics, exert their antibacterial effect by interfering with the synthesis of the bacterial cell wall. These antibiotics tend to be "irreversible" inhibitors of cell wall biosynthesis and they are usually bactericidal at concentrations close to their bacteriostatic levels. Cephalosporins are widely used for treating bacterial infections. They are highly effective antibiotics and have low toxicity.

Synthesis and Antimicrobial Evaluation of New Cephalosporin Derivatives Containing Cyclic Disulfide Moieties

“…On the other hand, the presence of amino-thiadiazol side chains represents a key structural unit for the 4th and 5th generation derivatives, which demonstrated an increased activity against Gram-negative strains . To introduce the zwitterionic properties in cephalosporin, the modification at the C3′-position of the cepham ring was done with the incorporation of the quaternary ammonium moiety . Pyridinium substitution, found in several clinically used antibiotics of 1st and 3rd generations, was chosen using 4-(aminomethyl)­pyridine, which is suitable for introducing the desired linkers via amide-bond formation.…”

Synthesis and antimicrobial evaluation of new cephalosporin derivatives containing cyclic disulfide moieties

“…29 To introduce the zwitterionic properties in cephalosporin the modification at the C3’-position of the cepham ring was done with the incorporation of the quaternary ammonium moiety. 30 Pyridinium substitution, found in several clinically used antibiotics of 1 st and 3 rd generation, was chosen using 4-(aminomethyl)pyridine, which is suitable for introducing the desired linkers via amide bond formation.…”

Patent Review of Manufacturing Routes to Fifth-Generation Cephalosporin Drugs. Part 1, Ceftolozane

“…The first-generation cephalosporin drugs were primarily active against Gram-positive bacteria such as Staphylococci . By the 1970s resistance to the first-generation cephalosporin drugs had become widespread due to evolution of bacterial β-lactamase enzymes, which hydrolyze the β-lactam ring to render the drugs ineffective.…”

“…The zwitterionic motif is more common in the fourth- and fifth-generation cephalosporins (cefpirome and ceftolozane), which have improved efficacy against resistant organisms. The fifth-generation cephalosporins are broad spectrum drugs that are also active against methicillin-resistant Staphylococcus aureus (MRSA) infections …”