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Record Information
Version2.0
Creation Date2009-07-21 20:27:09 UTC
Update Date2014-12-24 20:25:51 UTC
Accession NumberT3D2825
Identification
Common NameBenzthiazide
ClassSmall Molecule
DescriptionBenzthiazide is used to treat hypertension and edema. Like other thiazides, benzthiazide promotes water loss from the body (diuretics). They inhibit Na+/Cl- reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue.
Compound Type
  • Amide
  • Amine
  • Antihypertensive Agent
  • Diuretic
  • Drug
  • Ether
  • Metabolite
  • Organic Compound
  • Organochloride
  • Stimulant
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
3-((Benzylthio)methyl)-6-chloro-7-sulfamoyl-2H-benzo-1,2,4-thiadiazine 1,1-dioxide
3-Benzylthiomethyl-6-chloro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide
3-Benzylthiomethyl-6-chloro-7-sulfamoyl-1,2,4-benzothiadiazine 1,1-dioxide
6-chloro-1,1-dioxo-3-(Phenylmethylsulfanylmethyl)-4H-benzo[e][1,2,4]thiadiazine-7-sulfonamide
6-chloro-7-Sulfamoyl-3-benzylthiomethyl-2H-1,2,4-benzothiadiazine 1,1-dioxide
Aquatag
Benzothiazide
Benzotiazida
Benzthiazid
Benzthiazidum
Benztiazide
Dihydrex
Diucen
Edemax
Exna
Foven
Chemical FormulaC15H14ClN3O4S3
Average Molecular Mass431.937 g/mol
Monoisotopic Mass430.983 g/mol
CAS Registry Number91-33-8
IUPAC Name3-[(benzylsulfanyl)methyl]-6-chloro-1,1-dioxo-4H-1λ⁶,2,4-benzothiadiazine-7-sulfonamide
Traditional Nameregulon
SMILESNS(=O)(=O)C1=CC2=C(C=C1Cl)N=C(CSCC1=CC=CC=C1)NS2(=O)=O
InChI IdentifierInChI=1S/C15H14ClN3O4S3/c16-11-6-12-14(7-13(11)25(17,20)21)26(22,23)19-15(18-12)9-24-8-10-4-2-1-3-5-10/h1-7H,8-9H2,(H,18,19)(H2,17,20,21)
InChI KeyInChIKey=NDTSRXAMMQDVSW-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as 1,2,4-benzothiadiazine-1,1-dioxides. These are aromatic heterocyclic compounds containing a 1,2,4-benzothiadiazine ring system with two S=O bonds at the 1-position.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassThiadiazines
Sub ClassBenzothiadiazines
Direct Parent1,2,4-benzothiadiazine-1,1-dioxides
Alternative Parents
Substituents
  • 1,2,4-benzothiadiazine-1,1-dioxide
  • Aryl chloride
  • Aryl halide
  • Monocyclic benzene moiety
  • Organosulfonic acid amide
  • Imidolactam
  • Benzenoid
  • Organic sulfonic acid or derivatives
  • Organosulfonic acid or derivatives
  • Sulfonyl
  • Aminosulfonyl compound
  • Amidine
  • Azacycle
  • Dialkylthioether
  • Thioether
  • Sulfenyl compound
  • Organic oxide
  • Organosulfur compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Hydrocarbon derivative
  • Organic nitrogen compound
  • Organic oxygen compound
  • Organopnictogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point210-211°C
Boiling PointNot Available
Solubility8.91 mg/L
LogP1.73
Predicted Properties
PropertyValueSource
Water Solubility0.013 g/LALOGPS
logP2.26ALOGPS
logP1.84ChemAxon
logS-4.5ALOGPS
pKa (Strongest Acidic)8.77ChemAxon
pKa (Strongest Basic)1.25ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area118.69 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity104.14 m³·mol⁻¹ChemAxon
Polarizability41.5 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0006-9242000000-15561d025e3aa0c753082017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-001l-6202900000-2a70b9803c4b86c5dd1f2016-08-02View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00ko-9567100000-99dca328e8d7361a3afc2016-08-02View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-01vo-9551000000-d1e207308294a5deee082016-08-02View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0iki-2069300000-96a7d5e7dc1269a420442016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-004r-9128100000-4954efc1704bdde450092016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-004i-9010000000-d24b3facbec316c46e122016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-0009000000-ef28da9b71b01c96fb7a2021-09-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4i-0009000000-8007d10d85565090d5492021-09-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0fb9-9520000000-542b3b8a75568a776f6a2021-09-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-001i-0001900000-e655f017360118b76da12021-09-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-001i-3101900000-f89180b83227d57566b22021-09-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0006-9000000000-688382bcfe309825184b2021-09-24View Spectrum
MSMass Spectrum (Electron Ionization)splash10-06r6-9624000000-532194fb14045a87f8de2014-09-20View Spectrum
Toxicity Profile
Route of ExposureAbsorbed in the digestive tract.
Mechanism of ToxicityAs a diuretic, benzthiazide inhibits active chloride reabsorption at the early distal tubule via the Na-Cl cotransporter, resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like benzthiazide also inhibit sodium ion transport across the renal tubular epithelium through binding to the thiazide sensitive sodium-chloride transporter. This results in an increase in potassium excretion via the sodium-potassium exchange mechanism. The antihypertensive mechanism of benzthiazide is less well understood although it may be mediated through its action on carbonic anhydrases in the smooth muscle or through its action on the large-conductance calcium-activated potassium (KCa) channel, also found in the smooth muscle.
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the treatment of high blood pressure and management of edema.
Minimum Risk LevelNot Available
Health EffectsUsing large amounts of these drugs can result in a condition known as amphetamine psychosis -- which can result in auditory, visual and tactile hallucinations, intense paranoia, irrational thoughts and beliefs, delusions, and mental confusion.
SymptomsSymptoms of overdose include nausea, vomiting, fatigue, urinary problems and drowsiness.
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00562
HMDB IDHMDB14702
PubChem Compound ID2343
ChEMBL IDCHEMBL1201039
ChemSpider ID2253
KEGG IDC07759
UniProt IDNot Available
OMIM ID
ChEBI ID3047
BioCyc IDNot Available
CTD IDNot Available
Stitch IDBenzthiazide
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkNot Available
References
Synthesis Reference

Samuel M. Fainberg, Porfirio F. Perez, “Stable solution of benzthiazide (3-[benzythiol methyl]-6-chloro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide) suitable for parenteral administration and process of preparation.” U.S. Patent US4022894, issued May 10, 1977.

MSDST3D2825.pdf
General References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Voltage-gated potassium channel activity
Specific Function:
Potassium channel activated by both membrane depolarization or increase in cytosolic Ca(2+) that mediates export of K(+). It is also activated by the concentration of cytosolic Mg(2+). Its activation dampens the excitatory events that elevate the cytosolic Ca(2+) concentration and/or depolarize the cell membrane. It therefore contributes to repolarization of the membrane potential. Plays a key role in controlling excitability in a number of systems, such as regulation of the contraction of smooth muscle, the tuning of hair cells in the cochlea, regulation of transmitter release, and innate immunity. In smooth muscles, its activation by high level of Ca(2+), caused by ryanodine receptors in the sarcoplasmic reticulum, regulates the membrane potential. In cochlea cells, its number and kinetic properties partly determine the characteristic frequency of each hair cell and thereby helps to establish a tonotopic map. Kinetics of KCNMA1 channels are determined by alternative splicing, phosphorylation status and its combination with modulating beta subunits. Highly sensitive to both iberiotoxin (IbTx) and charybdotoxin (CTX).
Gene Name:
KCNMA1
Uniprot ID:
Q12791
Molecular Weight:
137558.115 Da
References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
General Function:
Zinc ion binding
Specific Function:
Reversible hydration of carbon dioxide. Can hydrates cyanamide to urea.
Gene Name:
CA1
Uniprot ID:
P00915
Molecular Weight:
28870.0 Da
References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
General Function:
Zinc ion binding
Specific Function:
Reversible hydration of carbon dioxide.
Gene Name:
CA12
Uniprot ID:
O43570
Molecular Weight:
39450.615 Da
References
  1. Temperini C, Cecchi A, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors. Comparison of chlorthalidone, indapamide, trichloromethiazide, and furosemide X-ray crystal structures in adducts with isozyme II, when several water molecules make the difference. Bioorg Med Chem. 2009 Feb 1;17(3):1214-21. doi: 10.1016/j.bmc.2008.12.023. Epub 2008 Dec 24. [19119014 ]
General Function:
Zinc ion binding
Specific Function:
Essential for bone resorption and osteoclast differentiation (By similarity). Reversible hydration of carbon dioxide. Can hydrate cyanamide to urea. Involved in the regulation of fluid secretion into the anterior chamber of the eye. Contributes to intracellular pH regulation in the duodenal upper villous epithelium during proton-coupled peptide absorption. Stimulates the chloride-bicarbonate exchange activity of SLC26A6.
Gene Name:
CA2
Uniprot ID:
P00918
Molecular Weight:
29245.895 Da
References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
General Function:
Zinc ion binding
Specific Function:
Reversible hydration of carbon dioxide. May stimulate the sodium/bicarbonate transporter activity of SLC4A4 that acts in pH homeostasis. It is essential for acid overload removal from the retina and retina epithelium, and acid release in the choriocapillaris in the choroid.
Gene Name:
CA4
Uniprot ID:
P22748
Molecular Weight:
35032.075 Da
References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
General Function:
Zinc ion binding
Specific Function:
Reversible hydration of carbon dioxide. Participates in pH regulation. May be involved in the control of cell proliferation and transformation. Appears to be a novel specific biomarker for a cervical neoplasia.
Gene Name:
CA9
Uniprot ID:
Q16790
Molecular Weight:
49697.36 Da
References
  1. Temperini C, Cecchi A, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors. Comparison of chlorthalidone, indapamide, trichloromethiazide, and furosemide X-ray crystal structures in adducts with isozyme II, when several water molecules make the difference. Bioorg Med Chem. 2009 Feb 1;17(3):1214-21. doi: 10.1016/j.bmc.2008.12.023. Epub 2008 Dec 24. [19119014 ]
General Function:
Transporter activity
Specific Function:
Key mediator of sodium and chloride reabsorption in this nephron segment, accounting for a significant fraction of renal sodium reabsorption.
Gene Name:
SLC12A3
Uniprot ID:
P55017
Molecular Weight:
113138.04 Da
References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]