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Record Information
Version2.0
Creation Date2014-09-11 05:15:40 UTC
Update Date2014-12-24 20:26:56 UTC
Accession NumberT3D4765
Identification
Common NameTolazamide
ClassSmall Molecule
DescriptionA sulphonylurea hypoglycemic agent with actions and uses similar to those of chlorpropamide.
Compound Type
  • Amide
  • Drug
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
1-(hexahydro-1-Azepinyl)-3-P-tolylsulfonylurea
1-(hexahydro-1H-Azepin-1-yl)-3-(P-tolylsulfonyl)urea
4-(P-Tolylsulfonyl)-1,1-hexamethylenesemicarbazide
BRN 1323565
CCRIS 591
Desumide
Diabewas
EINECS 214-588-3
Esulin
N-(P-Toluenesulfonyl)-n'-hexamethyleniminourea
N-{[(hexahydro-1H-azepin-1-yl)-amino]carbonyl}-4-methylbenzenesulfonamide
Norglycin
Tolanase
Tolazamid
Tolazamida
Tolazamidum
Tolinase
U 17835
U-17835
Chemical FormulaC14H21N3O3S
Average Molecular Mass311.400 g/mol
Monoisotopic Mass311.130 g/mol
CAS Registry Number1156-19-0
IUPAC Name1-(azepan-1-yl)-3-(4-methylbenzenesulfonyl)urea
Traditional Nametolazamide
SMILESCC1=CC=C(C=C1)S(=O)(=O)NC(O)=NN1CCCCCC1
InChI IdentifierInChI=1S/C14H21N3O3S/c1-12-6-8-13(9-7-12)21(19,20)16-14(18)15-17-10-4-2-3-5-11-17/h6-9H,2-5,10-11H2,1H3,(H2,15,16,18)
InChI KeyInChIKey=OUDSBRTVNLOZBN-UHFFFAOYSA-N
Chemical Taxonomy
Description 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.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzenesulfonamides
Direct ParentBenzenesulfonamides
Alternative Parents
Substituents
  • Benzenesulfonamide
  • Tosyl compound
  • Benzenesulfonyl group
  • Azepane
  • Toluene
  • Sulfonylurea
  • Organic sulfonic acid or derivatives
  • Organosulfonic acid or derivatives
  • Aminosulfonyl compound
  • Sulfonyl
  • Hydrazone
  • Azacycle
  • Organoheterocyclic compound
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Organopnictogen compound
  • Organic oxygen compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point170-173°C
Boiling PointNot Available
Solubility65.4 mg/L (at 30°C)
LogP2.69
Predicted Properties
PropertyValueSource
Water Solubility0.31 g/LALOGPS
logP1.4ALOGPS
logP1.91ChemAxon
logS-3ALOGPS
pKa (Strongest Acidic)4.07ChemAxon
pKa (Strongest Basic)1.61ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area78.51 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity81.34 m³·mol⁻¹ChemAxon
Polarizability32.82 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0007-9530000000-1efba84cf35a7c3462e8JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableJSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-001i-0119000000-08f98037ec7196f2922fJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-00kg-6901000000-edb181b207ba0c040d5eJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-001i-0119000000-08f98037ec7196f2922fJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-00kg-6901000000-edb181b207ba0c040d5eJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 15V, Positivesplash10-03di-0209000000-bedb05b5a97e0908596dJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 30V, Positivesplash10-014i-4901000000-a1ee7e5f83476a046f2cJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 60V, Positivesplash10-014m-9400000000-3f489397c4cc0115550aJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 45V, Positivesplash10-014j-7900000000-2ef187297f5318cde541JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 90V, Negativesplash10-056r-9600000000-79b4a41348e060a885cbJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 45V, Positivesplash10-014j-7900000000-03a2caa6a6a16dcc961eJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 15V, Negativesplash10-0229-0908000000-8344640fb69c0a69b641JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 30V, Negativesplash10-00di-0900000000-9f30fc8ec61a1c86f54eJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 90V, Positivesplash10-006x-9000000000-7a341cee1d086348c0cdJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 75V, Positivesplash10-00r7-9100000000-3c4b583b1c32a728bc9fJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 75V, Negativesplash10-0a4i-4900000000-2be60e1fa0ecff75b17aJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 60V, Negativesplash10-05fr-1900000000-035f71a8c50843cec3a6JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03di-2916000000-f998a4bd881fca969a3aJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-03di-3900000000-073057c545546aaa0511JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0avm-9100000000-96cc995c9c21a62b0291JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03di-1927000000-6672f320a126a06c90deJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-03k9-1900000000-fc714c59b068c2d0bfbdJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00fr-8910000000-7907f8e51f6cee4e2e2eJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03di-0209000000-b918c838d9ee432978cfJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0007-9302000000-89635c793cbf932550abJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0006-9100000000-3d92be1e62349f90d27cJSpectraViewer
MSMass Spectrum (Electron Ionization)splash10-06r6-9500000000-41e71d724a7515763bb7JSpectraViewer | MoNA
Toxicity Profile
Route of ExposureRapidly and well absorbed from the gastrointestinal tract.
Mechanism of ToxicitySulfonylureas likely bind to ATP-sensitive potassium-channel receptors on the pancreatic cell surface, reducing potassium conductance and causing depolarization of the membrane. Depolarization stimulates calcium ion influx through voltage-sensitive calcium channels, raising intracellular concentrations of calcium ions, which induces the secretion, or exocytosis, of insulin.
MetabolismTolazamide is metabolized to five major metabolites ranging in hypoglycemic activity from 0 to 70%. Route of Elimination: Tolazamide is metabolized to five major metabolites ranging in hypoglycemic activity from 0% to 70%. They are excreted principally in the urine. Half Life: The average biological half-life of the drug is 7 hours.
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor use as an adjunct to diet to lower the blood glucose in patients with non-insulin dependent diabetes mellitus (Type II) whose hyperglycemia cannot be satisfactorily controlled by diet alone.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsOverdosage of sulfonylureas can produce hypoglycemia. Severe hypoglycemic reactions with coma, seizure, or other neurological impairment occur infrequently, but constitute medical emergencies requiring immediate hospitalization.
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00839
HMDB IDHMDB14977
PubChem Compound ID5503
ChEMBL IDCHEMBL817
ChemSpider ID5302
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI ID156131
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkTolazamide
References
Synthesis ReferenceNot Available
MSDST3D4765.pdf
General ReferencesNot Available
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Phosphatidylinositol-4,5-bisphosphate binding
Specific Function:
In the kidney, probably plays a major role in potassium homeostasis. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. This channel is activated by internal ATP and can be blocked by external barium.
Gene Name:
KCNJ1
Uniprot ID:
P48048
Molecular Weight:
44794.6 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. [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. [17016423 ]
  3. Szabo C, Salzman AL: Inhibition of ATP-activated potassium channels exerts pressor effects and improves survival in a rat model of severe hemorrhagic shock. Shock. 1996 Jun;5(6):391-4. [8799949 ]
  4. Asano K, Cortes P, Garvin JL, Riser BL, Rodriguez-Barbero A, Szamosfalvi B, Yee J: Characterization of the rat mesangial cell type 2 sulfonylurea receptor. Kidney Int. 1999 Jun;55(6):2289-98. [10354277 ]
General Function:
Transcriptional activator activity, rna polymerase ii distal enhancer sequence-specific binding
Specific Function:
Transcription activator that binds to antioxidant response (ARE) elements in the promoter regions of target genes. Important for the coordinated up-regulation of genes in response to oxidative stress. May be involved in the transcriptional activation of genes of the beta-globin cluster by mediating enhancer activity of hypersensitive site 2 of the beta-globin locus control region.
Gene Name:
NFE2L2
Uniprot ID:
Q16236
Molecular Weight:
67825.9 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.97 uMATG_NRF2_ARE_CISAttagene
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Zinc ion binding
Specific Function:
Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes.
Gene Name:
NR1I2
Uniprot ID:
O75469
Molecular Weight:
49761.245 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.81 uMATG_PXRE_CISAttagene
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]