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targets (6)
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Identification
Name Benzthiazide
Accession Number DB00562 (APRD00728)
Type small molecule
Groups approved
Description

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.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Synonyms Not Available
Salts Not Available
Brand names
Name Company
Aquatag
Benzothiazide
Benzthazide
Dihydrex
Diucen
Edemex
Exna
Exosalt
Fovane
Freeuril
Hydrine
Lemazide
Naclex
Pfizer 1393
Proaqua
Urese
First Prev Next Last
Brand mixtures Not Available
Categories
  • Antihypertensive Agents
  • Stimulants
  • Diuretics
CAS number 91-33-8
Weight Average: 431.937
Monoisotopic: 430.983495728
Chemical Formula C15H14ClN3O4S3
InChI Key InChIKey=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)
Plain Text
IUPAC Name
3-[(benzylsulfanyl)methyl]-6-chloro-1,1-dioxo-4H-1$l^{6},2,4-benzothiadiazine-7-sulfonamide
SMILES
NS(=O)(=O)C1=C(Cl)C=C2NC(CSCC3=CC=CC=C3)=NS(=O)(=O)C2=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Benzenesulfonamides
  • Sulfanilamides
Substructures
  • Ethers
  • Sulfonyls
  • Benzene and Derivatives
  • Aryl Halides
  • Benzenesulfonamides
  • Halobenzenes
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamidines
  • Thiadiazines
  • Sulfanilamides
  • Sulfonamides
  • Imines
  • Anilines
Pharmacology
Indication For the treatment of high blood pressure and management of edema.
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.
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
Toxicity Symptoms of overdose include nausea, vomiting, fatigue, urinary problems and drowsiness.
Affected organisms
  • Humans and other mammals
Pathways Not Available
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
Melting point 231.5 oC
Experimental Properties
Property Value Source
water solubility 8.91 mg/L PhysProp
logP 1.7 PhysProp
Predicted Properties
Property Value Source
water solubility 1.29e-02 g/l ALOGPS
logP 2.26 ALOGPS
logP 1.84 ChemAxon Molconvert
logS -4.5 ALOGPS
pKa 9.33 ChemAxon Molconvert
hydrogen acceptor count 6 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 118.69 ChemAxon Molconvert
rotatable bond count 5 ChemAxon Molconvert
refractivity 104.14 ChemAxon Molconvert
polarizability 41.5 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00651 Link_out
KEGG Compound C07759 Link_out
PubChem Compound 2343 Link_out
PubChem Substance 46506752 Link_out
ChemSpider 2253 Link_out
ChEBI 3047 Link_out
ChEMBL 3047 Link_out
Therapeutic Targets Database DAP000603 Link_out
PharmGKB PA448590 Link_out
ATC Codes Not Available
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Digoxin Possible electrolyte variations and arrhythmias
Lithium The thiazide diuretic, benzthiazide, may increase serum levels of lithium.
Food Interactions Not Available
Targets

1. Solute carrier family 12 member 3

Pharmacological action: yes
Actions: inhibitor

Electrically silent transporter system. Mediates sodium and chloride reabsorption

Organism class: human
UniProt ID: P55017 Link_out
Gene: SLC12A3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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

2. Carbonic anhydrase 1

Pharmacological action: unknown
Actions: inhibitor

Reversible hydration of carbon dioxide

Organism class: human
UniProt ID: P00915 Link_out
Gene: CA1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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

3. Carbonic anhydrase 2

Pharmacological action: unknown
Actions: inhibitor

Reversible hydration of carbon dioxide

Organism class: human
UniProt ID: P00918 Link_out
Gene: CA2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

4. Carbonic anhydrase 4

Pharmacological action: unknown
Actions: inhibitor

Reversible hydration of carbon dioxide. May stimulate the sodium/bicarbonate transporter activity of SLC4A4

Organism class: human
UniProt ID: P22748 Link_out
Gene: CA4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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

5. Carbonic anhydrase 9

Pharmacological action: unknown
Actions: inhibitor

Reversible hydration of carbon dioxide. May be involved in the control of cell proliferation and transformation. Appears to be a novel specific biomarker for a cervical neoplasia

Organism class: human
UniProt ID: Q16790 Link_out
Gene: CA9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2008 Dec 24. Pubmed

6. Carbonic anhydrase 12

Pharmacological action: unknown
Actions: inhibitor

Reversible hydration of carbon dioxide

Organism class: human
UniProt ID: O43570 Link_out
Gene: CA12 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2008 Dec 24. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 14, 2012 11:42