Cephalothin

Antibiotics. Cephaloridine and Cephalothin (Glaxo) were early thiophene-containing, cephalosporin antibiotics. They have largely been replaced by later products, of which Cefoxitin [35607-66-0] (Merck) (51) is the principal thiophene-containing example (see Antibiotics). 

Oxadethiacephalosporins. The first compound in which the sulfur of a cephalosporin was replaced by oxygen was 1-oxa-dethiacephalothin [54214-83-4] (64), C gH N20yS, (199) which is approximately twice as active as cephalothin (27) taking into account that the synthetic material was... 

Cephalosporins first entered the marketplace in 1964, when cephalothin (27) and cephaloridine (51), which are both injectable, were launched. By the late 1970s, the injectable cephalosporins had become important therapeutic agents in the hospitals. Also in 1964 the first oral cephalosporin, cephaloglycin [3577-01 -3] C gH N OgS, was launched only to be displaced by the end of the year by cephalexin (12). For years cephalexin was the leading oral cephalosporin on the market. It has since been displaced by cefaclor (13). With the advent of the more -lactamase stable cephalosporins such as cefoxitin (23) and cefuroxime (35), and the more potent agents such as cefotaxime (36) and other third-generation compounds, cephalosporins now dominate the antibiotic market worldwide. 

The substrate is amici11in for penicillinases and cephalothin for Cephases unless otherwise iadicated. The substrate is nitrocefin. 

Compared to penicillins, cephalosporins are generally effective against a broader range of organisms and are more resistant to /3-lactamases. /3-Lactamases are bacterial enzymes that efficiently hydrolyze /3-lactam antibiotics to inactive species in which the /3-lactam bond has been cleaved. Cephalothin was the first cephalosporin to be marketed and continues... 

Acylation of 7-ACA with 2-thienylacetylchloride gives the amide cephalothin (43). Displacement of the allylic acetyl group by pyridine affords the corresponding pyridinium salt cephalori-dine (44). Both these compounds constitute useful injectable antibiotics with some activity against bacteria resistant to penicillin by reason of penicillinase production. 

Aminocephalosporanic acid Cefazolin sodium Ceftizoxime Cephacetriie sodium Cephalogiycin Cephaloridine Cephalothin sodium Cephapirin sodium 2-Amino-5-chlorobenzonitrile Ciorazepate dipotassium 2-Amino-5-chlorobenzophenone Chlordiazepoxide HCi Pinazepam Prazepam... 

Benzyl- and Phenoxymethylpenicillins, Ampidllin, Carbenicillin Cephalosporin C Cephaloglycine, Cephaloridine, Cephalothin Hydrolysis Corresponding p-lactam ring cleavage products Escherichia coli Streptomyces aibus Pseudomonas aeruginosa Enterobacter cloacae Streptomyces sp. 

The class C enzymes have Mr values of 39,000 and exhibit more uniform properties. They hydrolyse benzyl- and phenoxymethyl penicillin relatively well (turn-over numbers of 20-70 s-1), ampicillin and amoxicillin 10- to 20-fold less rapidly and extremely poorly the other penicillins (generally due to low k3 values). The early cephalosporins (cephalothin,... 

Pharmaeokinetie properties of the cephalosporins depend to a considerable extent on their ehemieal nature, e.g. the substituent R. The 3-acetoxymethyl compounds such as cephalothin, cephapirin and cephacetrile are converted in vivo by esterases to the antibaeterially less aetive 3-hydroxymethyl derivatives and are excreted partly as such. The rapid exeretion means that such cephalosporins have a short half-life in the body. Replaeement of the 3-acetoxymethyl group by a variety of groups has rendered other eephalosporins mueh less prone to esterase attack. For example, cephaloridine has an internally eompensated betaine group at position 3 (R ) and is metabolically stable. 

Cephalosporins (e.g., cefazolin, cefoxitin, cefaclor, cephalexin, and cephalothin)... 

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