Identification

Name
Sulfametopyrazine
Accession Number
DB00664  (APRD00517)
Type
Small Molecule
Groups
Approved, Withdrawn
Description

Long-acting plasma-bound sulfonamide used for respiratory and urinary tract infections and also for malaria. [PubChem]

Structure
Thumb
Synonyms
  • Kelfizina
  • Solfametopirazina
  • Sulfalene
  • Sulfaleno
  • Sulfalenum
External IDs
AS-18908 / NSC-110433
Categories
UNII
T6BL4ZC15G
CAS number
152-47-6
Weight
Average: 280.303
Monoisotopic: 280.06301096
Chemical Formula
C11H12N4O3S
InChI Key
KXRZBTAEDBELFD-UHFFFAOYSA-N
InChI
InChI=1S/C11H12N4O3S/c1-18-11-10(13-6-7-14-11)15-19(16,17)9-4-2-8(12)3-5-9/h2-7H,12H2,1H3,(H,13,15)
IUPAC Name
4-amino-N-(3-methoxypyrazin-2-yl)benzene-1-sulfonamide
SMILES
COC1=NC=CN=C1NS(=O)(=O)C1=CC=C(N)C=C1

Pharmacology

Indication

For the treatment of urinary tract infection and chronic bronchitis.

Structured Indications
Not Available
Pharmacodynamics

Sulfametopyrazine is a sulfonamide antibiotic. The sulfonamides are synthetic bacteriostatic antibiotics with a wide spectrum against most gram-positive and many gram-negative organisms. However, many strains of an individual species may be resistant. Sulfonamides inhibit multiplication of bacteria by acting as competitive inhibitors of p-aminobenzoic acid in the folic acid metabolism cycle. Bacterial sensitivity is the same for the various sulfonamides, and resistance to one sulfonamide indicates resistance to all. Most sulfonamides are readily absorbed orally. However, parenteral administration is difficult, since the soluble sulfonamide salts are highly alkaline and irritating to the tissues. The sulfonamides are widely distributed throughout all tissues. High levels are achieved in pleural, peritoneal, synovial, and ocular fluids. Although these drugs are no longer used to treat meningitis, CSF levels are high in meningeal infections. Their antibacterial action is inhibited by pus.

Mechanism of action

Sulfametopyrazine is a competitive inhibitor of the bacterial enzyme dihydropteroate synthetase. Para-aminobenzoic acid (PABA), a substrate of the enzyme is prevented from binding. The inhibited reaction is necessary in these organisms for the synthesis of folic acid.

TargetActionsOrganism
ADihydropteroate synthetase
inhibitor
Plasmodium falciparum
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Gram negative, positive bacteria and plasmodium
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcepromazineThe serum concentration of Acepromazine can be increased when it is combined with Sulfametopyrazine.Approved, Vet Approved
AceprometazineThe serum concentration of Aceprometazine can be increased when it is combined with Sulfametopyrazine.Approved
AlimemazineThe serum concentration of Alimemazine can be increased when it is combined with Sulfametopyrazine.Approved, Vet Approved
ArtemetherThe risk or severity of adverse effects can be increased when Artemether is combined with Sulfametopyrazine.Approved
BL-1020The serum concentration of BL-1020 can be increased when it is combined with Sulfametopyrazine.Investigational
ChlorproethazineThe serum concentration of Chlorproethazine can be increased when it is combined with Sulfametopyrazine.Experimental
ChlorpromazineThe serum concentration of Chlorpromazine can be increased when it is combined with Sulfametopyrazine.Approved, Vet Approved
DapsoneThe risk or severity of adverse effects can be increased when Sulfametopyrazine is combined with Dapsone.Approved, Investigational
DexketoprofenThe risk or severity of adverse effects can be increased when Dexketoprofen is combined with Sulfametopyrazine.Approved, Investigational
FluphenazineThe serum concentration of Fluphenazine can be increased when it is combined with Sulfametopyrazine.Approved
LumefantrineThe risk or severity of adverse effects can be increased when Sulfametopyrazine is combined with Lumefantrine.Approved
MecamylamineThe risk or severity of adverse effects can be increased when Sulfametopyrazine is combined with Mecamylamine.Approved
MesoridazineThe serum concentration of Mesoridazine can be increased when it is combined with Sulfametopyrazine.Approved, Investigational
MethotrimeprazineThe serum concentration of Methotrimeprazine can be increased when it is combined with Sulfametopyrazine.Approved
Methylene blueThe serum concentration of Methylene blue can be increased when it is combined with Sulfametopyrazine.Approved, Investigational
MoricizineThe serum concentration of Moricizine can be increased when it is combined with Sulfametopyrazine.Approved, Investigational, Withdrawn
PerazineThe serum concentration of Perazine can be increased when it is combined with Sulfametopyrazine.Investigational
PerphenazineThe serum concentration of Perphenazine can be increased when it is combined with Sulfametopyrazine.Approved
ProchlorperazineThe serum concentration of Prochlorperazine can be increased when it is combined with Sulfametopyrazine.Approved, Vet Approved
PromazineThe serum concentration of Promazine can be increased when it is combined with Sulfametopyrazine.Approved, Vet Approved
PromethazineThe serum concentration of Promethazine can be increased when it is combined with Sulfametopyrazine.Approved
PropericiazineThe serum concentration of Propericiazine can be increased when it is combined with Sulfametopyrazine.Approved
PropiopromazineThe serum concentration of Propiopromazine can be increased when it is combined with Sulfametopyrazine.Vet Approved
ThiazinamThe serum concentration of Thiazinam can be increased when it is combined with Sulfametopyrazine.Experimental
ThiethylperazineThe serum concentration of Thiethylperazine can be increased when it is combined with Sulfametopyrazine.Withdrawn
ThioproperazineThe serum concentration of Thioproperazine can be increased when it is combined with Sulfametopyrazine.Approved
ThioridazineThe serum concentration of Thioridazine can be increased when it is combined with Sulfametopyrazine.Approved, Withdrawn
TrifluoperazineThe serum concentration of Trifluoperazine can be increased when it is combined with Sulfametopyrazine.Approved
TriflupromazineThe serum concentration of Triflupromazine can be increased when it is combined with Sulfametopyrazine.Approved, Vet Approved
VemurafenibThe risk or severity of QTc prolongation can be increased when Vemurafenib is combined with Sulfametopyrazine.Approved
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB14802
KEGG Drug
D01216
KEGG Compound
C12616
PubChem Compound
9047
PubChem Substance
46505111
ChemSpider
8695
ChEBI
32162
ChEMBL
CHEMBL1525826
Therapeutic Targets Database
DAP001199
PharmGKB
PA164747038
ATC Codes
J01ED02 — SulfaleneG01AE10 — Combinations of sulfonamides

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)176 °CPhysProp
water solubility4030 mg/LNot Available
logP0.70HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.406 mg/mLALOGPS
logP0.41ALOGPS
logP0.23ChemAxon
logS-2.8ALOGPS
pKa (Strongest Acidic)5.91ChemAxon
pKa (Strongest Basic)1.98ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area107.2 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity70.37 m3·mol-1ChemAxon
Polarizability27.12 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9797
Blood Brain Barrier+0.6436
Caco-2 permeable-0.5125
P-glycoprotein substrateNon-substrate0.748
P-glycoprotein inhibitor INon-inhibitor0.8708
P-glycoprotein inhibitor IINon-inhibitor0.9728
Renal organic cation transporterNon-inhibitor0.9066
CYP450 2C9 substrateNon-substrate0.6554
CYP450 2D6 substrateNon-substrate0.8908
CYP450 3A4 substrateNon-substrate0.7127
CYP450 1A2 substrateNon-inhibitor0.8964
CYP450 2C9 inhibitorNon-inhibitor0.831
CYP450 2D6 inhibitorNon-inhibitor0.9467
CYP450 2C19 inhibitorNon-inhibitor0.8826
CYP450 3A4 inhibitorNon-inhibitor0.8952
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6424
Ames testNon AMES toxic0.7455
CarcinogenicityNon-carcinogens0.8527
BiodegradationNot ready biodegradable0.9973
Rat acute toxicity1.9789 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9669
hERG inhibition (predictor II)Non-inhibitor0.7806
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as benzenesulfonamides. These are organic compounds containing a sulfonamide group that is S-linked to a benzene ring.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzenesulfonamides
Direct Parent
Benzenesulfonamides
Alternative Parents
Benzenesulfonyl compounds / Methoxypyrazines / Aniline and substituted anilines / Alkyl aryl ethers / Imidolactams / Sulfonyls / Organosulfonic acids and derivatives / Heteroaromatic compounds / Azacyclic compounds / Primary amines
show 3 more
Substituents
Benzenesulfonamide / Benzenesulfonyl group / Methoxypyrazine / Aniline or substituted anilines / Alkyl aryl ether / Pyrazine / Imidolactam / Organic sulfonic acid or derivatives / Organosulfonic acid or derivatives / Sulfonyl
show 15 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
pyrazines, sulfonamide, sulfonamide antibiotic (CHEBI:32162)

Targets

Kind
Protein
Organism
Plasmodium falciparum
Pharmacological action
Yes
Actions
Inhibitor
General Function
Dihydropteroate synthase activity
Specific Function
Not Available
Gene Name
Not Available
Uniprot ID
Q27738
Uniprot Name
Dihydropteroate synthetase
Molecular Weight
43370.845 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Brumfitt W, Hamilton-Miller JM: Reassessment of the rationale for the combinations of sulphonamides with diaminopyrimidines. J Chemother. 1993 Dec;5(6):465-9. [PubMed:8195839]

Drug created on June 13, 2005 07:24 / Updated on November 07, 2017 01:41