Chemical Properties
white to cream powder
Originator
Gantrisin,Roche,US,1949
Uses
Sulfisoxazole is a sulfonamide based antibacterial that exhibits activity against wide spectrum of gram-negative and gram-positive bacterium.
Definition
ChEBI: A sulfonamide antibacterial with an oxazole substituent. It has antibiotic activity against a wide range of gram-negative and gram-positive organisms.
Manufacturing Process
112 parts of 3,4-dimethyl-5-amino-isoxazole were dissolved in a mixture of
100 volume parts of pyridine and 200 volume parts of acetone. The mixture is
cooled with cold water and 240 parts p-acetamino-benzene sulfonic acid
chloride are added in small portions under stirring at temperatures of below
30°C. The mixture is left standing overnight at 20° to 30°C and then the 5-
acetamino-benzene-sulfonylamino-3,4-dimethyl-isoxazole is precipitated by the addition of water. Recrystallized from acetic acid or alcohol it forms small
prisms of the melting point 210°C.
100 parts of the 5-acetamino-benzene-sulfonyl-amino-3,4-dimethyl-isoxazole
are boiled under reflux with 500 volume parts 15 to 20% aqueous
hydrochloric acid for 30 to 45 minutes until all is dissolved. 500 parts
crystallized sodium acetate are added and the liquid left cooling for
crystallization. The sulfanilamido-3,4-dimethyl-isoxazole is sucked off, washed
with water and dried. In the pure state it forms white prisms with the melting
point of 193°C.
brand name
Gantrisin (Roche).
Therapeutic Function
Antibacterial
Antimicrobial activity
Like all examined sulfanilamides, this drug is effective in treating infections caused by
streptococci, gonococci, pneumococci, staphylococci, and also colon bacillus. However,
about 90% of it binds with proteins in the plasma after oral administration, and it diffuses mostly to tissues and tissue fluids, which makes it the drug of choice for many systemic infections. Synonyms of this drug are gantrisin, fultrxin, sulfazin, sulfolar, and
others.
General Description
Sulfisoxazole’s plasmahalf-life is 6 hours. This compound is a white, odorless,slightly bitter, crystalline powder. Its pKa is 5.0. At pH 6,this sulfonamide has a water solubility of 350 mg in100 mL, and its acetyl derivative has a solubility of 110 mgin 100 mL of water.Sulfisoxazole possesses the action and the uses of othersulfonamides and is used for infections involving sulfonamide-sensitive bacteria. It is claimed to be effective in thetreatment of Gram-negative urinary infections.
General Description
Odorless white to yellowish crystalline powder. Slightly bitter taste. Acid to litmus.
Air & Water Reactions
May be sensitive to prolonged exposure to air and light. Sensitive to heat. Slightly soluble in water.
Fire Hazard
Flash point data for Sulfisoxazole are not available; however, Sulfisoxazole is probably combustible.
Pharmaceutical Applications
3,4-Dimethyl-5-sulfanilamidoisoxazole. It is highly soluble,
even in acid urine. The spectrum and potency are typical of
the group. It is well absorbed, achieving a concentration of
around 20 mg/L 3–4 h after a 2 g oral dose.
Side effects are those common to other sulfonamides. It
is less prone than some other members of the group to cause
renal problems. Its principal use is in urinary tract infection,
and is present in some ophthalmic preparations.
Biological Activity
A selective ET A endothelin receptor antagonist (IC 50 values are 600 and 2200 nM for ET A and ET B receptors respectively).
Safety Profile
Mildly toxic by ingestion. An experimental teratogen. Questionable carcinogen. Mutation data reported. When heated to decomposition it emits very toxic fumes of SOx and NOx.
Synthesis
Sulfisoxazole, N1
-(3,4-dimethyl-5-isoxazolyl)sulfanilamide (33.1.19), is
synthesized by reacting 4-acetylaminobenzenesulfonyl chloride with 5-amino-3,
4-dimethylisoxazol (33.1.17), which is in turn synthesized by heterocyclization of 2-methylacetylacetonitrile with hydroxylamine, and subsequent acidic hydrolysis (hydrochloric acid)
of the protective acetyl group in the resulting product (33.1.18).
References
[1] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 17, p. 5254 - 5261
[2] DRP/DRBP Org.Chem.,
[3] Patent: DE819855, 1951,
