50-59-9 Usage
Description
This was derived by adding two side chains to the nucleus of
cephalothin, and has the formula 7-(2-thienyl acetamido)-3-(1-pyridylmethyl)-3-cephem-4-carboxylic acid betaine (Muggleton et al.,
1964). Cephaloridine was initially widely used, but it had two main
disadvantages. It was an unreliable antistaphylococcal drug, as it was
relatively easily hydrolyzed by Staphylococcus aureus beta-lactamase
(Laverdiere et al., 1978; Sabath, 1989). Second, cephaloridine was
nephrotoxic (Foord, 1975; Appel and Neu, 1977). Marketing of the
drug was discontinued in the USA in December 1980. Nowadays, this
drug is used very rarely, if at all.
Originator
Ceporin,Glaxo,UK,1964
Uses
Antibacterial agent.
Definition
ChEBI: A cephalosporin compound having pyridinium-1-ylmethyl and 2-thienylacetamido side-groups. A first-generation semisynthetic derivative of cephalosporin C.
Manufacturing Process
7-Aminocephalosporanic acid (5.00 g) which passed through a 100-mesh
sieve was suspended in boiling ethyl acetate (200 ml), and 2-thienylacetyl
chloride (Cagniant, Bull. Soc. Chim. France, 1949, 847) (4.42 g, 1.5 equiv.)
was added in ethyl acetate (20 ml). The mixture was boiled under reflux for
40 minutes, cooled, and filtered. Aniline (5.03 ml) was added, and after 1
hour the mixture was extracted with 3% sodium hydrogen carbonate solution
(1 x 150 ml, 2 x 100 ml, 1 x 50 ml) and the alkaline extracts washed with
ethyl acetate (3 x 100 ml). The aqueous solution was acidified to pH 1.2, and
extracted with ethyl acetate (2 x 150 ml). The ethyl acetate extract was
washed with water (4 x 40 ml), dried (MgSO4), and concentrated in vacuo to
low volume. The crude 7-2'-thienylacetamidocephalosporanic acid (2.5 g)
which separated was collected by filtration. Evaporation of the filtrate gave a
further 2.68 g (71%) of the product, which was purified by crystallization from
ethyl acetate, then aqueous acetone, MP 150°C to 157°C (decomp.).
7-2'-Thienylacetamidocephalosporanic acid (7.0 g) was suspended in water
(60 ml) and stirred with pyridine (7 ml) until the acid dissolved. The resulting
solution (pH 5.9) was kept at 35°C for 3 days, then filtered and extracted with
methylene chloride (4 x 60 ml). The methylene chloride extract was back-extracted with a little water and the total aqueous solutions were then
percolated through a column of Dowex 1 x 8 resin, (100 to 200 mesh, 150 g)
in the acetate form at pH 4.3. The column was washed with water until the
optical rotation of the eluate fell to zero and the eluate (500 ml) was freeze-dried. The residual white solid was dissolved in the minimum volume of
methanol and after a few minutes the pyridine derivative crystallized; this is
the cephaloridine product.
Brand name
Kefloridin (Lilly); Loridine
(Lilly);Cepalorin;Faredina;Latorex;Lauridin.
Therapeutic Function
Antibacterial
World Health Organization (WHO)
Cefaloridine, a semi-synthetic cephalosporin antibiotic, was
introduced into medicine in 1964 for the treatment of bacterial infections. It is
considered to be the most toxic of the cephalosporins, and for this reason is now
seldom used. Nevertheless, it still remains available in certain countries and the
World Health Organization is not aware of restrictive actions taken elsewhere.
Hazard
Moderately to very toxic.
Check Digit Verification of cas no
The CAS Registry Mumber 50-59-9 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 5 and 0 respectively; the second part has 2 digits, 5 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 50-59:
(4*5)+(3*0)+(2*5)+(1*9)=39
39 % 10 = 9
So 50-59-9 is a valid CAS Registry Number.
InChI:InChI=1/C19H17N3O4S2/c23-14(9-13-5-4-8-27-13)20-15-17(24)22-16(19(25)26)12(11-28-18(15)22)10-21-6-2-1-3-7-21/h1-8,15,18H,9-11H2,(H-,20,23,25,26)
50-59-9Relevant articles and documents
Alkaline hydrolysis of cephaloridine: an 1H - NMR study. Temperature dependence of the rate constants
Vilanova,Donoso,Munoz,Garcia Blanco
, p. 865 - 874 (2007/10/03)
A kinetic study on the basic hydrolysis of cephaloridine at pD = 10.5 was carried out by using the 1H - NMR technique. Epimerization at H7, a nucleophilic attack of hydroxyl ion on the β-lactam carbonyl group followed by the release of the pyridine molecule, and isomerization of the double bond at position 3 in the dihydrothiazine ring were the major reactions observed. Based on the results obtained, it should be emphasized that the presence of a pyridine group at 3′ results in a slightly increased formation constant for the exo methylene compound relative to other cephalosporins with different substituents at that position. The activation energy for the epimerization constant and the cleavage of the β-lactam ring at pD 10.5 was 21.2 kcal/mol
Synthesis of 3-functionalised cephalosporins by photoinitiated bromination. Transformations of 2,2,2-trichloroethyl 1S, 6R, 7R)-3-bromomethyl-7-formamidoceph-3-EM-4-carboxylate, 1-oxide
Cowley,Humber,Laundon,et al.
, p. 461 - 467 (2007/10/02)
The 3-bromomethyl derivative 2c, obtained by photoinitiated bromination of the corresponding 3-Me compound 1c, has been converted into the antibiotics cephalothin 18 and cephaloridine 20. Reaction of 2c with lithium dimethyl- and diphenyl-cuprate led to the intermediates 22 and 24 respectively. Further transformation of 24 provided the 3-benzyl derivative 27, an isostere of cephaloridine.
