Identification
- Generic Name
- Benzthiazide
- DrugBank Accession Number
- DB00562
- Background
Benzthiazide 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.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Benzthiazide (DB00562)
- Weight
- Average: 431.937
Monoisotopic: 430.983495728 - Chemical Formula
- C15H14ClN3O4S3
- Synonyms
- 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
- Benzothiazide
- Benzotiazida
- Benzthiazid
- Benzthiazide
- Benzthiazidum
- Benztiazide
- External IDs
- P 1393
Pharmacology
- Indication
For the treatment of high blood pressure and management of edema.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Benzthiazide 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.
- Mechanism of action
As 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.
Target Actions Organism ASolute carrier family 12 member 3 inhibitorHumans ACarbonic anhydrase inhibitorHumans UCarbonic anhydrase 1 inhibitorHumans UCarbonic anhydrase 2 inhibitorHumans UCarbonic anhydrase 4 inhibitorHumans UCarbonic anhydrase 9 inhibitorHumans UCarbonic anhydrase 12 inhibitorHumans - Absorption
Absorbed in the digestive tract.
- Volume of distribution
Not Available
- Protein binding
30%
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Symptoms of overdose include nausea, vomiting, fatigue, urinary problems and drowsiness.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Benzthiazide may increase the excretion rate of Abacavir which could result in a lower serum level and potentially a reduction in efficacy. Abciximab The therapeutic efficacy of Abciximab can be decreased when used in combination with Benzthiazide. Acarbose The therapeutic efficacy of Acarbose can be decreased when used in combination with Benzthiazide. Acebutolol The therapeutic efficacy of Acebutolol can be increased when used in combination with Benzthiazide. Aceclofenac The therapeutic efficacy of Benzthiazide can be decreased when used in combination with Aceclofenac. - Food Interactions
- Not Available
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- International/Other Brands
- Aquatag / Dihydrex / Diucen / Edemax / Exna / Foven
Categories
- ATC Codes
- G01AE10 — Combinations of sulfonamides
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound 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.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Thiadiazines
- Sub Class
- Benzothiadiazines
- Direct Parent
- 1,2,4-benzothiadiazine-1,1-dioxides
- Alternative Parents
- Organosulfonamides / Imidolactams / Benzene and substituted derivatives / Aryl chlorides / Aminosulfonyl compounds / Sulfenyl compounds / Dialkylthioethers / Azacyclic compounds / Amidines / Organopnictogen compounds show 3 more
- Substituents
- 1,2,4-benzothiadiazine-1,1-dioxide / Amidine / Aminosulfonyl compound / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Benzenoid / Dialkylthioether / Hydrocarbon derivative show 16 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- sulfonamide, benzothiadiazine (CHEBI:3047)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 1TD8J48L61
- CAS number
- 91-33-8
- InChI Key
- NDTSRXAMMQDVSW-UHFFFAOYSA-N
- InChI
- InChI=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)
- IUPAC Name
- 3-[(benzylsulfanyl)methyl]-6-chloro-1,1-dioxo-4H-1lambda6,2,4-benzothiadiazine-7-sulfonamide
- SMILES
- NS(=O)(=O)C1=CC2=C(C=C1Cl)N=C(CSCC1=CC=CC=C1)NS2(=O)=O
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.
US4022894- General References
- Not Available
- External Links
- Human Metabolome Database
- HMDB0014702
- KEGG Drug
- D00651
- KEGG Compound
- C07759
- PubChem Compound
- 2343
- PubChem Substance
- 46506752
- ChemSpider
- 2253
- BindingDB
- 50238676
- 19008
- ChEBI
- 3047
- ChEMBL
- CHEMBL1201039
- ZINC
- ZINC000003871698
- Therapeutic Targets Database
- DAP000603
- PharmGKB
- PA164776841
- Wikipedia
- Benzthiazide
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count
Pharmacoeconomics
- Manufacturers
- Solvay pharmaceuticals
- Private formulations inc
- Ah robins inc
- Pfizer laboratories div pfizer inc
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 210-211 McLamore, W.M. and Laubach, G.D.; U.S. Patent 3,111,517; November 19, 1963; assigned to Chas. Pfizer & Co., Inc. water solubility 8.91 mg/L Not Available logP 1.73 BERTHOD,A ET AL. (1999) pKa 6 BERTHOD,A ET AL. (1999) - Predicted Properties
Property Value Source Water Solubility 0.0121 mg/mL ALOGPS logP 2.25 ALOGPS logP 1.84 Chemaxon logS -4.6 ALOGPS pKa (Strongest Acidic) 9.18 Chemaxon pKa (Strongest Basic) -4.7 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 118.69 Å2 Chemaxon Rotatable Bond Count 5 Chemaxon Refractivity 104.14 m3·mol-1 Chemaxon Polarizability 41.5 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9593 Blood Brain Barrier - 0.8349 Caco-2 permeable - 0.705 P-glycoprotein substrate Substrate 0.5849 P-glycoprotein inhibitor I Non-inhibitor 0.7928 P-glycoprotein inhibitor II Non-inhibitor 0.5851 Renal organic cation transporter Non-inhibitor 0.6761 CYP450 2C9 substrate Non-substrate 0.7261 CYP450 2D6 substrate Non-substrate 0.8285 CYP450 3A4 substrate Non-substrate 0.557 CYP450 1A2 substrate Non-inhibitor 0.9046 CYP450 2C9 inhibitor Inhibitor 0.7652 CYP450 2D6 inhibitor Non-inhibitor 0.8733 CYP450 2C19 inhibitor Non-inhibitor 0.9026 CYP450 3A4 inhibitor Inhibitor 0.7959 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.681 Ames test Non AMES toxic 0.8436 Carcinogenicity Non-carcinogens 0.7729 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 1.6663 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9085 hERG inhibition (predictor II) Non-inhibitor 0.879
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 201.4652935 predictedDarkChem Lite v0.1.0 [M-H]- 186.41191 predictedDeepCCS 1.0 (2019) [M+H]+ 202.3666935 predictedDarkChem Lite v0.1.0 [M+H]+ 188.76993 predictedDeepCCS 1.0 (2019) [M+Na]+ 202.0038935 predictedDarkChem Lite v0.1.0 [M+Na]+ 195.08519 predictedDeepCCS 1.0 (2019)
Targets
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- 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
- Uniprot Name
- Solute carrier family 12 member 3
- Molecular Weight
- 113138.04 Da
References
- Blanchard A, Vallet M, Dubourg L, Hureaux M, Allard J, Haymann JP, de la Faille R, Arnoux A, Dinut A, Bergerot D, Becker PH, Courand PY, Baron S, Houillier P, Tack I, Devuyst O, Jeunemaitre X, Azizi M, Vargas-Poussou R: Resistance to Insulin in Patients with Gitelman Syndrome and a Subtle Intermediate Phenotype in Heterozygous Carriers: A Cross-Sectional Study. J Am Soc Nephrol. 2019 Aug;30(8):1534-1545. doi: 10.1681/ASN.2019010031. Epub 2019 Jul 8. [Article]
- Ellison DH: The thiazide-sensitive na-cl cotransporter and human disease: reemergence of an old player. J Am Soc Nephrol. 2003 Feb;14(2):538-40. [Article]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Zinc ion binding
- Specific Function
- Reversible hydration of carbon dioxide. Can hydrates cyanamide to urea.
Components:
References
- LEIBMAN KC, ALFORD D, BOUDET RA: Nature of the inhibition of carbonic anhydrase by acetazolamide and benzthiazide. J Pharmacol Exp Ther. 1961 Mar;131:271-4. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Zinc ion binding
- Specific Function
- Reversible hydration of carbon dioxide. Can hydrates cyanamide to urea.
- Gene Name
- CA1
- Uniprot ID
- P00915
- Uniprot Name
- Carbonic anhydrase 1
- Molecular Weight
- 28870.0 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- 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 in...
- Gene Name
- CA2
- Uniprot ID
- P00918
- Uniprot Name
- Carbonic anhydrase 2
- Molecular Weight
- 29245.895 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. [Article]
- 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. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- 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 an...
- Gene Name
- CA4
- Uniprot ID
- P22748
- Uniprot Name
- Carbonic anhydrase 4
- Molecular Weight
- 35032.075 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- 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 cervic...
- Gene Name
- CA9
- Uniprot ID
- Q16790
- Uniprot Name
- Carbonic anhydrase 9
- Molecular Weight
- 49697.36 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Zinc ion binding
- Specific Function
- Reversible hydration of carbon dioxide.
- Gene Name
- CA12
- Uniprot ID
- O43570
- Uniprot Name
- Carbonic anhydrase 12
- Molecular Weight
- 39450.615 Da
References
- 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. [Article]
Drug created at June 13, 2005 13:24 / Updated at December 02, 2023 06:52