723-46-6 Usage
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 lookchem of Dai Xiongfeng.
Chemical Properties
Different sources of media describe the Chemical Properties of 723-46-6 differently. You can refer to the following data:
1. 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.
2. solid
Uses
Different sources of media describe the Uses of 723-46-6 differently. You can refer to the following data:
1. 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.
2. An antibacterial drug. Sulfonamide antibiotic that blocks the synthesis of dihydrofolic acid by inhibiting the enzyme dihydropteroate synthase.
3. antibacterial, antipneumocystis
4. An antibacterial drug. Sulfonamide antibiotic that blocks the synthesis of dihydrofolic acid by inhibiting the enzyme dihydropteroate synthase.This compound is a contaminant of emerging concern (CECs).
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.
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.
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.
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.
Check Digit Verification of cas no
The CAS Registry Mumber 723-46-6 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 7,2 and 3 respectively; the second part has 2 digits, 4 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 723-46:
(5*7)+(4*2)+(3*3)+(2*4)+(1*6)=66
66 % 10 = 6
So 723-46-6 is a valid CAS Registry Number.
InChI:InChI=1/C10H11N3O3S/c1-7-6-10(12-16-7)13-17(14,15)9-4-2-8(11)3-5-9/h2-6H,11H2,1H3,(H,12,13)
723-46-6Relevant articles and documents
Reduction of sulfamethoxazole hydroxylamine (SMX-HA) by the mitochondrial amidoxime reducing component (mARC)
Ott, Gudrun,Plitzko, Birte,Krischkowski, Carmen,Reichmann, Debora,Bittner, Florian,Mendel, Ralf R.,Kunze, Thomas,Clement, Bernd,Havemeyer, Antje
, p. 1687 - 1695 (2014)
Under high dose treatment with sulfamethoxazole (SMX)/trimethoprim (TMP), hypersensitivity reactions occur with a high incidence. The mechanism of this adverse drug reaction is not fully understood. Several steps in the toxification pathway of SMX were investigated. The aim of our study was to investigate the reduction of sulfamethoxazole hydroxylamine (SMX-HA) in this toxification pathway, which can possibly be catalyzed by the mARC-containing N-reductive enzyme system. Western blot analyses of subcellular fractions of porcine tissue were performed with antibodies against mARC-1, mARC-2, cytochrome b5 type B, and NADH cytochrome b5 reductase. Incubations of porcine and human subcellular tissue fractions and of the heterologously expressed human components of the N-reductive enzyme system were carried out with SMX-HA. mARC-1 and mARC-2 knockdown was performed in HEK-293 cells. Kinetic parameters of the heterologously expressed human protein variants V96L, A165T, M187 K, C246S, D247H, and M268I of mARC-1 and G244S and C245W of mARC-2 and N-reductive activity of 2SF, D14G, K16E, and T22A of cytochrome b5 type B were analyzed. Western blot analyses were consistent with the hypothesis that the mARC-containing N-reductive enzyme system might be involved in the reduction of SMX-HA. In agreement with these results, highest reduction rates were found in mitochondrial subcellular fractions of porcine tissue and in the outer membrane vesicle (OMV) of human liver tissue. Knockdown studies in HEK-293 cells demonstrated that mARC-1 and mARC-2 were capable of reducing SMX-HA in cell metabolism. Investigations with the heterologously expressed human mARC-2 protein showed a higher catalytic efficiency toward SMX-HA than mARC-1, but none of the investigated human protein variants showed statistically significant differences of its N-reductive activity and was therefore likely to participate in the pathogenesis of hypersensitivity reaction under treatment with SMX. (Chemical Equation Presented).
Synthesis of calix[4]azacrown substituted sulphonamides with antioxidant, acetylcholinesterase, butyrylcholinesterase, tyrosinase and carbonic anhydrase inhibitory action
Akocak, Suleyman,Boga, Mehmet,Kalay, Erbay,Lolak, Nebih,Nocentini, Alessio,Oguz, Mehmet,Supuran, Claudiu T.,Yilmaz, Mustafa
, p. 1215 - 1223 (2020/05/27)
A series of novel calix[4]azacrown substituted sulphonamide Schiff bases was synthesised by the reaction of calix[4]azacrown aldehydes with different substituted primary and secondary sulphonamides. The obtained novel compounds were investigated as inhibitors of six human (h) isoforms of carbonic anhydrases (CA, EC 4.2.1.1). Their antioxidant profile was assayed by various bioanalytical methods. The calix[4]azacrown substituted sulphonamide Schiff bases were also investigated as inhibitors of acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and tyrosinase enzymes, associated with several diseases such as Alzheimer, Parkinson, and pigmentation disorders. The new sulphonamides showed low to moderate inhibition against hCAs, AChE, BChE, and tyrosinase enzymes. However, some of them possessed relevant antioxidant activity, comparable with standard antioxidants used in the study.
Industrial preparation method of Sinomin
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Paragraph 0015-0018, (2019/01/13)
The invention discloses an industrial preparation method of Sinomin. According to the industrial preparation method, 3-amino-5-methylisoxazole and diphenyl urea sulfonyl chloride are used as raw materials, under the condition of basicity, condensation reaction is performed at first, then hydrolysis, acidification, concentration under reduced pressure, centrifugation and drying are performed so asto prepare the Sinomin. The used raw materials are easy to obtain, the preparation method is low-cost, post-treatment is simple, the finished product does not need to be recrystallized, the reaction operation is highly safe, product purity is greater than or equal to 99.5%, the yield of the product is 92-95%, the preparation method does not contaminate environment heavily, so that the industrial preparation method is based on the principle of green chemistry, and is easy to industrialize.
