57-68-1 Usage
Uses
Used in Veterinary Medicine:
Sulfamethazine is used as an antibacterial agent for the treatment and prevention of bacterial infections in animals. It is particularly useful in combination sulfa therapy and is available under various brand names such as Calfspan Tablets, Sulka S Boluses, and SulfaSURE SR Bolus.
Used in Human Medicine (limited):
Although its use in human medicine is limited due to unpredictable handling by the human body, sulfamethazine is still utilized in combination sulfa therapy (in trisulfapyrimidines, USP) for the treatment of certain bacterial infections.
Used as a Contaminant of Emerging Concern (CECs):
Sulfamethazine is also recognized as a contaminant of emerging concern, highlighting the need for monitoring and managing its environmental impact.
Originator
Cremomethazine,MSD,US,1947
Manufacturing Process
A flask heated in an oil bath is filled with 600 ml water and 60 g (1 mol)
glacial acetic acid (or an equivalent quantity of diluted acetic acid). While
stirring 235 g (1.1 mols) anhydrous p-aminobenzenesulfonamidoguanidine (or
an equivalent quantity of a nonanhydrous product) and 122 g (1 mol) sodium
acetylacetonate 100% purity (or an equivalent quantity of product of a lower
purity) are introduced into the flask while stirring.The temperature of the reaction mixture is brought to 102°C to 103°C, the
mixture is further stirred at this temperature during 24 hours. The pH value of
the mixture, which should range between 5 and 6 is checked during the
reaction.On expiry of the reaction period heating is cut off, the mass being cooled or
allowed to cool down to 60°C.Filtering under suction is effected, the solids on the filter being washed with
100 ml water at 80°C.After drying of the product on the filter 256 g of 2-paminobenzenesulfonamido-
4,6-dimethylpyrimidine, melting point 196°C to
197°C, purity 99.5% are obtained. The output is 92% of the theory calculated
with respect to the sodium acetylacetonate employed.
Therapeutic Function
Antimicrobial
World Health Organization (WHO)
Sulfadimidine, a sulfonamide anti-infective agent, was introduced
in 1942 for the treatment of bacterial infections. The importance of sulfonamides
has subsequently decreased as a result of increasing resistance and their
replacement by antibiotics which are generally more active and less toxic. The
sulfonamides are known to cause serious adverse effects such as renal toxicity,
sometimes fatal exfoliative dermatitis and erythema multiforma and dangerous
adverse reactions affecting blood formation such as agranulocytosis and
haemolytic or aplastic anaemia. Sulfadimidine is still used in some countries as a
injectable or oral antimicrobial for susceptible infections.
Antimicrobial activity
This drug is used for pneumococcal, staphylococcal, and streptococcal infections as well
as for sepsis, gonorrhea, and other infectious diseases. Synonyms of this drug are sulfadiamezin and sulfadimidin.
Air & Water Reactions
Water solubility increases rapidly with increasing pH [Merck]. Insoluble in water.
Reactivity Profile
Sulfamethazine is sensitive to light and may also be sensitive to heat. The presence of oxygen and moisture may accelerate the effects of heat and light .
Fire Hazard
Flash point data for Sulfamethazine are not available; however, Sulfamethazine is probably combustible.
Pharmaceutical Applications
2-Sulfanilamido-4,6-methylpyrimidine (syn: sulphamethazine,
sulfamezathine). A water-soluble compound, unstable
on exposure to light. It is usually administered by
mouth and is a component of some triple sulfonamide
combinations.
The spectrum is typical of the group, but sulfadimidine
exhibits relatively low potency. It is well absorbed
after oral administration. It is extensively metabolized,
predominantly
by acetylation. The mean plasma half-life
(1.5–5 h) varies with acetylator status.
In addition to side effects common to the group, a serious
interaction between ciclosporin (cyclosporin A) and sulfadimidine,
leading to reduced ciclosporin levels, has been
reported.
Biochem/physiol Actions
Sulfamethazine is an antimicrobial sulfur drug that blocks the synthesis of dihydrofolic acid by inhibiting the enzyme dihydropteroate synthase. Sulfamethazine is a competitive inhibitor of bacterial para-aminobenzoic acid (PABA), which is required for bacterial synthesis of folic acid. It induces CYP3A4 expression and is acetylated by N-acetyltransferase. It exhibits sex dependent pharmacokinetics, metabolized by the male specific isoform CYP2C11. Sulfamethazine is bacteriostatic.
Safety Profile
Moderately toxic by intravenous and intraperitoneal routes. Experimental teratogenic and reproductive effects. Questionable carcinogen with experimental tumorigenic data. When heated to decomposition it emits very toxic fumes of SOx and NOx.
Synthesis
Sulfamethazine, N1
-(4,6-dimethyl-2-pyrimidinyl)sulfanilamide (33.1.13),
is also synthesized in the aforementioned manner by reacting 4-acetylaminobenzenesulfonyl
chloride with 2-amino-4,6-dimethylpyrimidine, which is in turn synthesized by condensing
acetylacetone with guanidine followed by hydrolysis of the acetylamino group using a base.
Purification Methods
Crystallise it from dioxane or aqueous dioxane. [Caldwell et al. J Am Chem Soc 63 2188 1941, Roblin et al. J Am Chem Soc 64 567 1942, Beilstein 25 III/IV 2215.]
Check Digit Verification of cas no
The CAS Registry Mumber 57-68-1 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 5 and 7 respectively; the second part has 2 digits, 6 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 57-68:
(4*5)+(3*7)+(2*6)+(1*8)=61
61 % 10 = 1
So 57-68-1 is a valid CAS Registry Number.
InChI:InChI=1/C12H14N4O2S/c1-8-7-9(2)15-12(14-8)16-19(17,18)11-5-3-10(13)4-6-11/h3-7H,13H2,1-2H3,(H,14,15,16)
57-68-1Relevant articles and documents
Synthesis, antimicrobial, anti-cancer and in silico studies of new urea derivatives
Sroor, Farid M.,Othman, Abdelmageed M.,Tantawy, Mohamed A.,Mahrous, Karima F.,El-Naggar, Mostafa E.
, (2021/05/10)
The reaction of an alkyl or aryl isocyanates with some primary amines in acetonitrile at room temperature afforded the corresponding alkyl- and aryl-urea derivatives. All the prepared urea compounds have been elucidated by FTIR, NMR, and elemental analysis. The compounds 1 and 3 were confirmed by single-crystal X-ray diffraction. The 4-tolylsulfonyl isocyanate reacted with the aryl amines 1, 2, 3, and 2,4-dichloroaniline to afford the corresponding sulfonylurea derivatives 5–8. Likewise, the reaction of the isocyanates with 2,4-dichloroaniline, 5-methyl isoxazole-3-amine, and 2-aminothiazole derivatives gave the corresponding urea derivatives 9–17. All the prepared compounds 5–17 were tested in vitro as anti-microbial and anti-HepG2 agents. Moreover, analyzing gene expression of TP53-exon4 and TP53-exon7, DNA damage values, and DNA fragmentation percentages have been discussed. The compounds 5 and 8 recorded the highest activity against the tested microbial strains with maximum activity against C. albicans (50 mm) and B. mycoides (40 mm), respectively. The compounds 5 inhibited the growth of E. coli, S. aureus, and C. Albicans at the MIC level of 0.0489 μM, while the compound 8 was able to inhibit the visible growth of E. coli and C. albicans at MIC value of 3.13 μM and S. aureus at 0.3912 μM. In the same line, compound 5 showed the best cytotoxic activity against the HepG2 cell line (IC50 = 4.25 μM) compared to 5 fluorouracil with IC50 = 316.25 μM. Expression analysis of liver cancer related to a gene including TP53-exon4 and TP53-exon7 was used in HepG2 Liver cancer cell lines using RT-qPCR. The expression values of TP53-exon4 and TP53-exon7 genes were decreased. The DNA damage values and DNA fragmentation percentages were increased significantly (P 0.01) in the treated HepG2 (5) sample compared with the negative control. Docking studies were performed for the synthetic compounds against 2 bacterial proteins (DNA gyrase subunit B, and penicillin binding protein 1a) that are known targets for some antibiotics, and one cell division protein kinase 2 (CDK2) as target for anticancer drugs.
Process for formulating a synthetic drug for use in animal feed, and resulting formulation
-
, (2008/06/13)
A method of formulating a synthetic drug for use in animal feed, for the purpose of reducing carry-over of the synthetic drug to subsequent lots of animal feed in the feed mill.
