Identification
NameSulfamethazine
Accession NumberDB01582
TypeSmall Molecule
GroupsApproved, Vet Approved
Description

A sulfanilamide anti-infective agent. It has a spectrum of antimicrobial action similar to other sulfonamides. [PubChem]

Structure
Thumb
Synonyms
(P-Aminobenzolsulfonyl)-2-amino-4,6-dimethylpyrimidin
2-(4-Aminobenzenesulfonamido)-4,6-dimethylpyrimidine
2-(P-Aminobenzenesulfonamido)-4,6-dimethylpyrimidine
2-Sulfanilamido-4,6-dimethylpyrimidine
4-Amino-N-(2,6-dimethyl-4-pyrimidinyl)benzenesulfonamide
4-Amino-N-(4,6-dimethyl-pyrimidin-2-yl)-benzenesulfonamide
4-amino-N-(4,6-Dimethylpyrimidin-2-yl)benzenesulfonamide
4,6-Dimethyl-2-sulfanilamidopyrimidine
6-(4'-Aminobenzol-sulfonamido)-2,4-dimethylpyrimidin
N-(4,6-Dimethyl-2-pyrimidyl)sulfanilamide
N(1)-(4,6-Dimethyl-2-pyrimidinyl)sulfanilamide
N(1)-(4,6-Dimethyl-2-pyrimidyl)sulfanilamide
SMZ
Sulfadimethyldiazine
Sulfadimethylpyrimidine
Sulfadimidina
Sulfadimidine
Sulfadimidinum
Sulfametazina
Sulfametazyny
Sulfamezathine
Sulphadimethylpyrimidine
Sulphamethazine
External IDs BN-2409 / NSC-67457 / NSC-683529
Product Ingredients
IngredientUNIICASInChI KeyDetails
Sulfamethazine sodium7Z13P9Q95C 1981-58-4NGIVTUVVBWOTNT-UHFFFAOYSA-NDetails
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixtures
NameLabellerIngredients
Trisulfaminic SusShepherd Pharmaceuticals Inc.
Trisulfaminic TabShepherd Pharmaceuticals Inc.
Categories
UNII48U51W007F
CAS number57-68-1
WeightAverage: 278.33
Monoisotopic: 278.083746402
Chemical FormulaC12H14N4O2S
InChI KeyASWVTGNCAZCNNR-UHFFFAOYSA-N
InChI
InChI=1S/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)
IUPAC Name
4-amino-N-(4,6-dimethylpyrimidin-2-yl)benzene-1-sulfonamide
SMILES
CC1=CC(C)=NC(NS(=O)(=O)C2=CC=C(N)C=C2)=N1
Pharmacology
Indication

For the treatment bacterial infections causing bronchitis, prostatitis and urinary tract infections.

Structured Indications Not Available
Pharmacodynamics

Sulfamethazine is a sulfonamide drug that inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid (PABA) for binding to dihydropteroate synthetase (dihydrofolate synthetase). Sulfamethazine is bacteriostatic in nature. Inhibition of dihydrofolic acid synthesis decreases the synthesis of bacterial nucleotides and DNA.

Mechanism of action

Sulfonamides inhibit the enzymatic conversion of pteridine and p-aminobenzoic acid (PABA) to dihydropteroic acid by competing with PABA for binding to dihydrofolate synthetase, an intermediate of tetrahydrofolic acid (THF) synthesis. THF is required for the synthesis of purines and dTMP and inhibition of its synthesis inhibits bacterial growth. Pyrimethamine and trimethoprim inhibit dihydrofolate reductase, another step in THF synthesis, and therefore act synergistically with the sulfonamides.

TargetKindPharmacological actionActionsOrganismUniProt ID
Dihydropteroate synthaseProteinyes
inhibitor
Escherichia coli (strain K12)P0AC13 details
Related Articles
Absorption

Rapidly absorbed following oral administration.

Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
Toxicity

Sulfamethazine may cause nausea, vomiting, diarrhea and hypersensitivity reactions. Hematologic effects such as anemia, agranulocytosis, thrombocytopenia and hemolytic anemia in patients with glucose-6-phosphate dehydrogenase deficiency may also occur. Sulfamethoxazole may displace bilirubin from albumin binding sites causing jaundice or kernicterus in newborns.

Affected organismsNot Available
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions
DrugInteractionDrug group
DexketoprofenThe risk or severity of adverse effects can be increased when Dexketoprofen is combined with Sulfamethazine.Approved
MecamylamineThe risk or severity of adverse effects can be increased when Sulfamethazine is combined with Mecamylamine.Approved
Food Interactions
  • Do not take calcium, aluminium, magnesium or iron supplements within 2 hours of taking this medication.
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesJ01EE05 — Sulfadimidine and trimethoprimJ01EB03 — SulfadimidineG01AE10 — Combinations of sulfonamides
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (73 KB)
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
2RecruitingTreatmentModerate, refractory Atopic dermatitis1
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
SuspensionOral
TabletOral
Prices
Unit descriptionCostUnit
Sulfamethazine powder1.74USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point (°C)198.5 °CPhysProp
water solubility1500 mg/L (at 29 °C)MERCK INDEX (1983); at pH 7
logP0.89BIOBYTE (1995)
pKa7.59SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.23 mg/mLALOGPS
logP0.43ALOGPS
logP0.65ChemAxon
logS-3.1ALOGPS
pKa (Strongest Acidic)6.99ChemAxon
pKa (Strongest Basic)2.04ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area97.97 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity73.38 m3·mol-1ChemAxon
Polarizability28.8 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9908
Blood Brain Barrier+0.9275
Caco-2 permeable+0.6203
P-glycoprotein substrateNon-substrate0.8692
P-glycoprotein inhibitor INon-inhibitor0.888
P-glycoprotein inhibitor IINon-inhibitor0.9281
Renal organic cation transporterNon-inhibitor0.8643
CYP450 2C9 substrateNon-substrate0.7791
CYP450 2D6 substrateNon-substrate0.909
CYP450 3A4 substrateNon-substrate0.7382
CYP450 1A2 substrateNon-inhibitor0.9368
CYP450 2C9 inhibitorNon-inhibitor0.8639
CYP450 2D6 inhibitorNon-inhibitor0.9661
CYP450 2C19 inhibitorNon-inhibitor0.9481
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8112
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.9182
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.1354 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9434
hERG inhibition (predictor II)Non-inhibitor0.8515
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Spectra
Mass Spec (NIST)Download (8.13 KB)
Spectra
Spectrum TypeDescriptionSplash Key
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0pk9-2970000000-abb9e31dc053c1d21884View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0zi0-0590000000-2e8e1e943731aa842e16View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0kmi-0950000000-9e91e580b580594989a0View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-00di-0920000000-216c25f077b257c6979dView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-00di-0900000000-127b8b6e862f77ce8c13View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-004i-0090000000-4841dadd912e95b736ceView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-000i-0910000000-fbf298bf77be3c0c7d4aView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-004i-0090000000-92cfb9d3f1565228cb1bView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-004i-0690000000-6900746badf188ab1500View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0abi-1910000000-5d3d9cc74470d1da9673View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0abc-3900000000-10a72542fb3fce7c8e67View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-05fu-5900000000-0ad8b99c3c478536a01eView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0avl-8900000000-d30171fd393f511058d6View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-004i-0090000000-bf48a8bbb6d06696db15View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-004i-0690000000-4789a5291d234b5d0375View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0abi-1910000000-2364d173d7cd8dae0c76View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0abc-3900000000-330131b76908d2b6ec6dView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-05fu-6900000000-0437ddca2816d4b382adView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0603-7900000000-71014d7adacf773403b4View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as aminobenzenesulfonamides. These are organic compounds containing a benzenesulfonamide moiety with an amine group attached to the benzene ring.
KingdomChemical entities
Super ClassOrganic compounds
ClassBenzenoids
Sub ClassBenzene and substituted derivatives
Direct ParentAminobenzenesulfonamides
Alternative ParentsBenzenesulfonyl compounds / Aniline and substituted anilines / Pyrimidines and pyrimidine derivatives / Primary aromatic amines / Organosulfonamides / Heteroaromatic compounds / Aminosulfonyl compounds / Azacyclic compounds / Organopnictogen compounds / Organic oxides
SubstituentsAminobenzenesulfonamide / Benzenesulfonyl group / Aniline or substituted anilines / Primary aromatic amine / Pyrimidine / Organosulfonic acid amide / Organic sulfonic acid or derivatives / Organosulfonic acid or derivatives / Sulfonyl / Aminosulfonyl compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptorssulfonamide, pyrimidines, sulfonamide antibiotic (CHEBI:102265 )

Targets

Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
yes
Actions
inhibitor
General Function:
Metal ion binding
Specific Function:
Catalyzes the condensation of para-aminobenzoate (pABA) with 6-hydroxymethyl-7,8-dihydropterin diphosphate (DHPt-PP) to form 7,8-dihydropteroate (H2Pte), the immediate precursor of folate derivatives.
Gene Name:
folP
Uniprot ID:
P0AC13
Molecular Weight:
30614.855 Da
References
  1. Hong YL, Hossler PA, Calhoun DH, Meshnick SR: Inhibition of recombinant Pneumocystis carinii dihydropteroate synthetase by sulfa drugs. Antimicrob Agents Chemother. 1995 Aug;39(8):1756-63. [PubMed:7486915 ]
  2. Friaza V, Morilla R, Respaldiza N, de la Horra C, Calderon EJ: Pneumocystis jiroveci dihydropteroate synthase gene mutations among colonized individuals and Pneumocystis pneumonia patients from Spain. Postgrad Med. 2010 Nov;122(6):24-8. doi: 10.3810/pgm.2010.11.2219. [PubMed:21084778 ]
  3. Thijssen HH: A simplified radioassay method of dihydropteroate synthetase activity in Escherichia coli and its application for an inhibition study of p-aminobenzoi acid derivatives. Anal Biochem. 1973 Jun;53(2):579-85. [PubMed:4577373 ]

Enzymes

Kind
Protein
Organism
Mycobacterium tuberculosis
Pharmacological action
unknown
Actions
substrate
General Function:
Catalyzes the transfer of the acetyl group from acetyl coenzyme A to the free amino group of arylamines and hydrazines (PubMed:18795795). Is able to utilize not only acetyl-CoA, but also n-propionyl-CoA and acetoacetyl-CoA as acyl donors, although at a lower rate (PubMed:19014350). As acetyl-CoA and propionyl-CoA are products of cholesterol catabolism and the nat gene is likely present in the same operon than genes involved in cholesterol degradation, this enzyme could have a role in the utilization and regulation of these CoA species (PubMed:19014350).
Specific Function:
Arylamine n-acetyltransferase activity
Gene Name:
nat
Uniprot ID:
P9WJI5
Molecular Weight:
31028.88 Da
References
  1. Derewlany LO, Knie B, Koren G: Arylamine N-acetyltransferase activity of the human placenta. J Pharmacol Exp Ther. 1994 May;269(2):756-60. [PubMed:8182542 ]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Toxic substance binding
Specific Function:
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood. Major zinc transporter in plasma, typically binds about 80% of all plasma zinc.
Gene Name:
ALB
Uniprot ID:
P02768
Molecular Weight:
69365.94 Da
References
  1. Bratlid D, Bergan T: Displacement of albumin-bound antimicrobial agents by bilirubin. Pharmacology. 1976;14(5):464-72. [PubMed:1031216 ]
  2. Angelakou A, Valsami G, Koupparis M, Macheras P: Use of 1-anilino-8-napthalenesulphonate as an ion probe for the potentiometric study of the binding of sulphonamides to bovine serum albumin and plasma. J Pharm Pharmacol. 1993 May;45(5):434-8. [PubMed:8099962 ]
Drug created on August 29, 2007 08:54 / Updated on July 18, 2017 17:00