T3DB: Tolazamide

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (3)XML

Targets (3)

Record Information

Version

2.0

Creation Date

2014-09-11 05:15:40 UTC

Update Date

2014-12-24 20:26:56 UTC

Accession Number

T3D4765

Identification

Common Name

Tolazamide

Class

Small Molecule

Description

A sulphonylurea hypoglycemic agent with actions and uses similar to those of chlorpropamide.

Compound Type

Amide
Drug
Metabolite
Organic Compound
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

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 Formula

C₁₄H₂₁N₃O₃S

Average Molecular Mass

311.400 g/mol

Monoisotopic Mass

311.130 g/mol

CAS Registry Number

1156-19-0

IUPAC Name

1-(azepan-1-yl)-3-(4-methylbenzenesulfonyl)urea

Traditional Name

tolazamide

SMILES

CC1=CC=C(C=C1)S(=O)(=O)NC(O)=NN1CCCCCC1

InChI Identifier

InChI=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 Key

InChIKey=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.

Kingdom

Organic compounds

Super Class

Benzenoids

Class

Benzene and substituted derivatives

Sub Class

Benzenesulfonamides

Direct Parent

Benzenesulfonamides

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 Framework

Aromatic heteromonocyclic compounds

External Descriptors

N-sulfonylurea (CHEBI:9613 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Not Available

Biological Roles

Not Available

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	170-173°C
Boiling Point	Not Available
Solubility	65.4 mg/L (at 30°C)
LogP	2.69

Predicted Properties

Property	Value	Source
Water Solubility	0.31 g/L	ALOGPS
logP	1.4	ALOGPS
logP	1.91	ChemAxon
logS	-3	ALOGPS
pKa (Strongest Acidic)	4.07	ChemAxon
pKa (Strongest Basic)	1.61	ChemAxon
Physiological Charge	-1	ChemAxon
Hydrogen Acceptor Count	4	ChemAxon
Hydrogen Donor Count	2	ChemAxon
Polar Surface Area	78.51 Å²	ChemAxon
Rotatable Bond Count	2	ChemAxon
Refractivity	81.34 m³·mol⁻¹	ChemAxon
Polarizability	32.82 Å³	ChemAxon
Number of Rings	2	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-0007-9530000000-1efba84cf35a7c3462e8	2017-09-01	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-qTof , Positive	splash10-001i-0119000000-08f98037ec7196f2922f	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-qTof , Positive	splash10-00kg-6901000000-edb181b207ba0c040d5e	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - , positive	splash10-001i-0119000000-08f98037ec7196f2922f	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - , positive	splash10-00kg-6901000000-edb181b207ba0c040d5e	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 15V, Positive	splash10-03di-0209000000-bedb05b5a97e0908596d	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 30V, Positive	splash10-014i-4901000000-a1ee7e5f83476a046f2c	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 60V, Positive	splash10-014m-9400000000-3f489397c4cc0115550a	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 45V, Positive	splash10-014j-7900000000-2ef187297f5318cde541	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 90V, Negative	splash10-056r-9600000000-79b4a41348e060a885cb	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 45V, Positive	splash10-014j-7900000000-03a2caa6a6a16dcc961e	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 15V, Negative	splash10-0229-0908000000-8344640fb69c0a69b641	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 30V, Negative	splash10-00di-0900000000-9f30fc8ec61a1c86f54e	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 90V, Positive	splash10-006x-9000000000-7a341cee1d086348c0cd	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 75V, Positive	splash10-00r7-9100000000-3c4b583b1c32a728bc9f	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 75V, Negative	splash10-0a4i-4900000000-2be60e1fa0ecff75b17a	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 60V, Negative	splash10-05fr-1900000000-035f71a8c50843cec3a6	2021-09-20	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-03di-2916000000-f998a4bd881fca969a3a	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-03di-3900000000-073057c545546aaa0511	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0avm-9100000000-96cc995c9c21a62b0291	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-03di-1927000000-6672f320a126a06c90de	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-03k9-1900000000-fc714c59b068c2d0bfbd	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-00fr-8910000000-7907f8e51f6cee4e2e2e	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-03di-0209000000-b918c838d9ee432978cf	2021-10-11	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0007-9302000000-89635c793cbf932550ab	2021-10-11	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0006-9100000000-3d92be1e62349f90d27c	2021-10-11	View Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-06r6-9500000000-41e71d724a7515763bb7	2014-09-20	View Spectrum

Toxicity Profile

Route of Exposure

Rapidly and well absorbed from the gastrointestinal tract.

Mechanism of Toxicity

Sulfonylureas 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.

Metabolism

Tolazamide 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 Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

For 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 Level

Not Available

Health Effects

Not Available

Symptoms

Overdosage of sulfonylureas can produce hypoglycemia. Severe hypoglycemic reactions with coma, seizure, or other neurological impairment occur infrequently, but constitute medical emergencies requiring immediate hospitalization.

Treatment

Not Available

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

HMDB ID

PubChem Compound ID

ChEMBL ID

ChemSpider ID

KEGG ID

Not Available

UniProt ID

Not Available

OMIM ID

ChEBI ID

156131

BioCyc ID

Not Available

CTD ID

Not Available

Stitch ID

Not Available

PDB ID

Not Available

ACToR ID

Not Available

Wikipedia Link

Tolazamide

References

Synthesis Reference

Not Available

MSDS

T3D4765.pdf

General References

Not Available

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. ATP-sensitive inward rectifier potassium channel 1

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

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
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 ]
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 ]
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 ]

Target Details

2. Nuclear factor erythroid 2-related factor 2

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

Type	Value	Assay Type	Assay Source
AC50	0.97 uM	ATG_NRF2_ARE_CIS	Attagene

References

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 ]

Target Details

3. Nuclear receptor subfamily 1 group I member 2

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

Type	Value	Assay Type	Assay Source
AC50	1.81 uM	ATG_PXRE_CIS	Attagene

References

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 ]

Tolazamide (T3D4765)

Structure for T3D4765: Tolazamide

Targets

References

Binding/Activity Constants

References

Binding/Activity Constants

References