Basic information Brand Name(s) in US Sulfonamide drugs Mechanism of action Chemical Properties Uses Production method Safety Supplier Related
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Sulfamethoxazole

Basic information Brand Name(s) in US Sulfonamide drugs Mechanism of action Chemical Properties Uses Production method Safety Supplier Related

Sulfamethoxazole Basic information

Product Name:
Sulfamethoxazole
Synonyms:
  • 3-(p-aminophenylsulfonamido)-5-methylisoxazole
  • 3-(para-Aminophenylsulphonamido)-5-methylisoxazole
  • 3-Sulfanilamido-5-methylisoxazole
  • 3-Sulphanilamido-5-methylisoxazole
  • 4-amino-n-(5-methyl-3-isoxazolyl)-benzenesulfonamid
  • 5-Methyl-3-sulfanilamidoisoxazole
  • 5-methyl-3-sulfanylamidoisoxazole
  • 5-Methyl-3-sulfonylamidoisoxazole
CAS:
723-46-6
MF:
C10H11N3O3S
MW:
253.28
EINECS:
211-963-3
Product Categories:
  • GANTANOL
  • Antibiotics for Research and Experimental Use
  • Biochemistry
  • Sulfonamides (Antibiotics for Research and Experimental Use)
  • Amines
  • Heterocycles
  • Intermediates & Fine Chemicals
  • Pharmaceuticals
  • Sulfur & Selenium Compounds
Mol File:
723-46-6.mol
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Sulfamethoxazole Chemical Properties

Melting point:
166 °C
Boiling point:
482℃
Density 
1.3915 (rough estimate)
refractive index 
1.6630 (estimate)
Flash point:
>110°(230°F)
storage temp. 
0-6°C
solubility 
Practically insoluble in water, freely soluble in acetone, sparingly soluble in ethanol (96 per cent). It dissolves in dilute solutions of sodium hydroxide and in dilute acids.
form 
neat
pka
pKa 5.60±0.05 (Uncertain)
Water Solubility 
Soluble in ethanol or acetone. Very slightly soluble in water
Sensitive 
Light Sensitive
Merck 
14,8918
BRN 
6732984
Stability:
Stable, but light sensitive. Incompatible with strong oxidizing agents.
InChIKey
JLKIGFTWXXRPMT-UHFFFAOYSA-N
CAS DataBase Reference
723-46-6(CAS DataBase Reference)
IARC
3 (Vol. Sup 7, 79) 2001
NIST Chemistry Reference
Sulfanilamide, n1-(5-methyl-3-isoxazolyl)-(723-46-6)
EPA Substance Registry System
Sulfamethoxazole (723-46-6)
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Safety Information

Hazard Codes 
Xi,Xn
Risk Statements 
36/37/38-43-22
Safety Statements 
26-36-36/37/39-22
WGK Germany 
2
RTECS 
WP0700000
Hazard Note 
Irritant
TSCA 
Yes
HazardClass 
IRRITANT
HS Code 
29350090
Hazardous Substances Data
723-46-6(Hazardous Substances Data)
Toxicity
LD50 orally in mice: 3662 mg/kg (Yamamoto)

MSDS

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Sulfamethoxazole Usage And Synthesis

Brand Name(s) in US

Gantanol

Sulfonamide drugs

Sulfa drugs have a relative broad antimicrobial spectrum and have certain inhibitory effect against most Gram-positive bacteria and gram-negative bacteria. However, different sulfonamide drugs have different extent of antibacterial efficacy. With the wide application of sulfonamide drugs, it will also be easy to lead to resistant strains; in particular the opportunity of resistant Staphylococcus aureus will be even higher than other kinds of resistant strains.
According to the absorption situations after oral administration, the sulfonamide drugs can be classified into two categories, the first category is easily absorbed sulfonamide drugs, which is characterized by rapid absorption. Generally, their plasma concentrations can reach peak at 2-4 hours after the administration (5 hour for long-acting drugs). This kind of sulfonamide drugs are mainly used for systemic infections. Another kind of drugs is hardly or poorly absorbed after oral administration with most of them being excreted through the intestinal tract and is mainly used for treating intestinal infections.
Sulfamethoxazole is a broad-spectrum antibiotic with particularly strong efficacy on Staphylococcus aureus and Escherichia coli and can be used for the treatment of urinary tract infections and fowl cholera. Sulfamethoxazole belongs to a systemic, moderate sulfonamide drug. It can compete with PABA through taking effect on the bacterial in vivo dihydrofolate synthase, preventing the bacterial synthesis of dihydrofolate and thereby inhibiting the bacterial growth and reproduction. It, together with other three kinds of sulfonamide drugs: sulfadiazine, sulfisoxazole and trisulfapyrimidine are currently excellent drugs for the treatment of nocardiosis. It has a half-life of 10 to 12 hours and can be partially acetylated. This product, although has the number of required medication be less than sulfisoxazole (2 times per day instead of four times), but its acetylated metabolites has a low solubility in the urine so the likelihood of large crystals formation in urine is bit higher. Patients should maintain enough hydrated conditions (the daily adult urine output should be not less than 1,500ml). When being used in combination with the synergist trimethoprim, its antibacterial activity can get significantly enhanced. Sulfamethoxazole compound (sulfamethoxazole/trimethoprim namely SMZ/TMP) can often give better efficacy than monotherapy (see dihydrofolate reductase inhibitors). Clinically it is commonly used for the treatment of urinary tract infections, respiratory tract infections, typhoid, and salmonella infections, Pneumocystis carinii echinococcosis and nocardiosis. It can also be used for preventing meningococcal meningitis. Some clinicians advocate use minocycline, erythromycin or ampicillin in combination with sulfamethoxazole to treat such infections. However, there has been no clinical data for proving that combination therapy is superior to single administration of sulfonamide. Sulfamethoxazole compound (TMP/SMZ), minocycline (Minocin) and amikacin can also be used for the treatment of nocardia infection.

Mechanism of action

It is known that bacterial can synthesize thymidine, purine and finally synthesize DNA and need folic acid derivatives, tetrahydrofolate as cofactors. Most bacterial cells can’t allow the penetration of folic acid and instead needs the synthesis through aminobenzoic acid (PABA). Sulfonamide has a similar structure to PABA and thus can competitively inhibit the synthesis of the direct precursor of dihydrofolate, dihy-dropteroic acid through the reaction between PABA and pteridine. Mammalian cells, instead, is not inhibited since they require preformed folate and is not capable of synthesizing this product.
Treatment concentration of sulfonamide drug sulfamethoxazole is primarily bacteriostatic agents. However, when the bacteria is grown in the medium containing purine, amino aicd but very low concentration of thymine, the sulfonamide drugs can produce a bactericidal effect, that is, "thymine lethal defect". This bactericidal effect has been demonstrated in human blood and urine (Then and Angehrn, 1973 A and B; see also Pratt and Fekety, 1986).
The effect of sulfonamide drug-induced inhibition of bacterial cell growth can be reversed upon supplement in vitro of some substances (such as thymidine, purines, methionine and serine) to the growth medium. This may have important clinical significance. Because the pus generated by cells destruction may contain a large amount of these substances. It is therefore, upon purulent infection, the effect of the drug may be inhibited probably due to the presence of such substances. Furthermore, for the in vitro susceptibility testing, the medium can’t contain PABA for which even in trace amount, the test results can be disturbed.
The above information is edited by the chemicalbook of Dai Xiongfeng.

Chemical Properties

It is white crystalline powder and is odorless with slightly bitter taste. It has a melting point of 168 ℃. It is very slightly soluble in water, soluble in dilute acid, dilute alkali or ammonia.

Uses

As an antimicrobial agent, it is particularly effective in treating Staphylococcus aureus and E. coli. It is mainly used for the treatment of fowl cholera.
It can be used as anti-infective drug and can be used for the treatment and prevention of acute and chronic urinary tract infections, respiratory infections, intestinal infections, Salmonella infections, children acute otitis media, and meningitis.

Production method

It can be produced from 5-methyl-isobutyl-3-carboxamide via degradation, condensation and hydrolysis successively.
Use 5-methyl-isobutyl-3-carboxamide as raw materials, it is degraded into 5-methyl-isoxazol-3 amine under the action of sodium hypochlorite solution, then condense with para-acetamidophenoxymethyl chloride to generate 3-(p-acetamide benzenesulfonamido)-5-methylisoxazole with further hydrolysis under alkaline conditions to give 3-(p-amino benzenesulfonamido)-5-methylisoxazole.

Description

Like sulfisoxazole, this drug is effective in treating infections caused by streptococci, gonococci, pneumococci, staphylococci as well as colon bacillus. Unlike sulfisoxazole, only about 70% of it binds with proteins in the plasma after oral administration, and it diffuses mostly to tissues and tissue fluids. However, since it is removed much slower than sulfisoxazole, it does not require frequent administration and is also the drug of choice for many systemic infections. Moreover, it is an ingredient of a combined drug named bactrim, biseptol, and so on (which will be examined later on), which has a fixed correlation with trimethoprim. Synonyms of this drug are gantanol, sinomin, sulfisomezole, and others.

Chemical Properties

solid

Uses

An antibacterial drug. Sulfonamide antibiotic that blocks the synthesis of dihydrofolic acid by inhibiting the enzyme dihydropteroate synthase.

Uses

antibacterial, antipneumocystis

Definition

ChEBI: An isoxazole (1,2-oxazole) compound having a methyl substituent at the 5-position and a 4-aminobenzenesulfonamido group at the 3-position.

brand name

Gantanol (Roche); Urobak (Shionogi).

Antimicrobial activity

The intrinsic activity is similar to that of sulfadiazine.

General Description

Sulfamethoxazole’s plasma half-life is 11 hours. Sulfamethoxazole is a sulfonamide drug closely relatedto sulfisoxazole in chemical structure and antimicrobial activity.It occurs as a tasteless, odorless, almost white crystallinepowder. The solubility of sulfamethoxazole in the pHrange of 5.5 to 7.4 is slightly lower than that of sulfisoxazole but higher than that of sulfadiazine, sulfamerazine, or sulfamethazine.Following oral administration, sulfamethoxazole is notabsorbed as completely or as rapidly as sulfisoxazole, andits peak blood level is only about 50% as high.

General Description

Crystals or white powder.

Air & Water Reactions

Insoluble in water.

Fire Hazard

Flash point data for Sulfamethoxazole are not available but Sulfamethoxazole is probably non-flammable.

Pharmaceutical Applications

This is the sulfonamide component of co-trimoxazole. It is slightly soluble in water.

Pharmacokinetics

Oral absorption: 85%
Cmax 800 mg oral: c.50 mg/L after 3–6 h
Plasma half-life: 6–20 h
Volume of distribution: 12–18 L
Plasma protein binding: 65%
Penetration of extravascular sites, including the CSF, is good. It crosses the placenta and achieves levels in breast milk of about 10% of the simultaneous plasma concentration. It is extensively metabolized, but about 30% of the dose is excreted unchanged in urine so that high concentrations are achieved.

Clinical Use

Sulfamethoxazole is used only in combination with the diaminopyrimidine trimethoprim.

Side effects

Unwanted effects are those common to sulfonamides. In addition, benign intracranial hypertension has been reported in children. Most side effects of co-trimoxazole are thought to be attributable to the sulfonamide component.

Safety Profile

Moderately toxic by ingestion and intraperitoneal routes. Questionable carcinogen with experimental tumorigenic data. When heated to decomposition it emits very toxic fumes of NOx and SOx.

Chemical Synthesis

Sulfamethoxazole, N1 -(5-methyl-3-isoxazolyl)sulfanilamide (33.1.20), is synthesized by a completely analogous scheme, except by using 3-amino-5-methylisoxazol as the heterocyclic component.

SulfamethoxazoleSupplier

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