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targets (5)
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Identification
Name Quinethazone
Accession Number DB01325
Type small molecule
Groups approved
Description

Quinethazone (INN, brand name Hydromox) is a thiazide diuretic used to treat hypertension. Common side effects include dizziness, dry mouth, nausea, and low potassium levels.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Chinetazone [dcit]
  • Chinethazonum
  • Quinetazona [inn-spanish]
  • Quinethazon
  • Quinethazonum [inn-latin]
Brand names
  • Aquamox
  • Hydromox
  • Idrokin
Brand name mixtures
  • Hydromox R (Quinethazone + Reserpine)
Categories
  • Antihypertensive Agents
  • Diuretics, Thiazide
CAS number 73-49-4
Weight Average: 289.739
Monoisotopic: 289.028789662
Chemical Formula C10H12ClN3O3S
InChI Key InChIKey=AGMMTXLNIQSRCG-UHFFFAOYSA-N
InChI
InChI=1S/C10H12ClN3O3S/c1-2-9-13-7-4-6(11)8(18(12,16)17)3-5(7)10(15)14-9/h3-4,9,13H,2H2,1H3,(H,14,15)(H2,12,16,17)
Plain Text
IUPAC Name
7-chloro-2-ethyl-4-oxo-1,2,3,4-tetrahydroquinazoline-6-sulfonamide
SMILES
CCC1NC(=O)C2=C(N1)C=C(Cl)C(=C2)S(N)(=O)=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Not Available
Classes
  • Benzenesulfonamides
  • Sulfanilamides
  • Lactams
Substructures
  • Amino Ketones
  • Sulfonyls
  • Benzene and Derivatives
  • Aryl Halides
  • Carboxylic Acids and Derivatives
  • Benzenesulfonamides
  • Halobenzenes
  • Aminals and Derivatives
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Sulfanilamides
  • Sulfonamides
  • Lactams
  • Benzoyl Derivatives
  • Benzamides
  • Anilines
Pharmacology
Indication Used to treat hypertension.
Pharmacodynamics Quinethazone is a thiazide diuretic used to treat hypertension. It inhibits 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, quinethazone 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 quinethazone 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 quinethazone 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 Not Available
Volume of distribution Not Available
Protein binding Not Available
Metabolism
Route of elimination Not Available
Half life Not Available
Clearance Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00091 Quinethazone Pathway SMP00091
Pharmacoeconomics
Manufacturers
  • Lederle laboratories div american cyanamid co
Packagers Not Available
Dosage forms
Form Route Strength
Tablet Oral
Prices Not Available
Patents Not Available
Properties
State solid
Melting point 251 oC
Experimental Properties
Property Value Source
water solubility 0.15 mg/mL at 25 oC [YALKOWSKY,SH & DANNENFELSER,RM (1992)] PhysProp
Predicted Properties
Property Value Source
water solubility 2.51e+00 g/l ALOGPS
logP 1.60 ALOGPS
logP 1.19 ChemAxon Molconvert
logS -2.06 ALOGPS
pKa 12.75 ChemAxon Molconvert
hydrogen acceptor count 4 ChemAxon Molconvert
hydrogen donor count 3 ChemAxon Molconvert
polar surface area 101.29 ChemAxon Molconvert
rotatable bond count 2 ChemAxon Molconvert
refractivity 69.34 ChemAxon Molconvert
polarizability 27.30 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00461 Link_out
KEGG Compound C07342 Link_out
PubChem Compound 6307 Link_out
PubChem Substance 46507280 Link_out
ChemSpider 6068 Link_out
BindingDB 25898 Link_out
Therapeutic Targets Database DAP000955 Link_out
PharmGKB PA451208 Link_out
Drug Product Database 0 Link_out
Wikipedia http://en.wikipedia.org/wiki/Quinethazone Link_out
ATC Codes
  • C03BA02
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions
  • Take with food to increase bioavailability.
Targets

1. Carbonic anhydrase 1

Pharmacological action: yes
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. Temperini C, Cecchi A, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors. Sulfonamide diuretics revisited—old leads for new applications? Org Biomol Chem. 2008 Jul 21;6(14):2499-506. Epub 2008 May 29. Pubmed
  2. Temperini C, Cecchi A, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors. Interaction of indapamide and related diuretics with 12 mammalian isozymes and X-ray crystallographic studies for the indapamide-isozyme II adduct. Bioorg Med Chem Lett. 2008 Apr 15;18(8):2567-73. Epub 2008 Mar 20. Pubmed
  3. Supuran CT: Diuretics: from classical carbonic anhydrase inhibitors to novel applications of the sulfonamides. Curr Pharm Des. 2008;14(7):641-8. Pubmed

2. Carbonic anhydrase 2

Pharmacological action: yes
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. Temperini C, Cecchi A, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors. Sulfonamide diuretics revisited—old leads for new applications? Org Biomol Chem. 2008 Jul 21;6(14):2499-506. Epub 2008 May 29. Pubmed
  2. Temperini C, Cecchi A, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors. Interaction of indapamide and related diuretics with 12 mammalian isozymes and X-ray crystallographic studies for the indapamide-isozyme II adduct. Bioorg Med Chem Lett. 2008 Apr 15;18(8):2567-73. Epub 2008 Mar 20. Pubmed
  3. Supuran CT: Diuretics: from classical carbonic anhydrase inhibitors to novel applications of the sulfonamides. Curr Pharm Des. 2008;14(7):641-8. Pubmed

3. Solute carrier family 12 member 1

Pharmacological action: yes
Actions: inhibitor

Electrically silent transporter system. Mediates sodium and chloride reabsorption. Plays a vital role in the regulation of ionic balance and cell volume

Organism class: human
UniProt ID: Q13621 Link_out
Gene: SLC12A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Duarte JD, Cooper-DeHoff RM: Mechanisms for blood pressure lowering and metabolic effects of thiazide and thiazide-like diuretics. Expert Rev Cardiovasc Ther. 2010 Jun;8(6):793-802. Pubmed
  2. Gamba G: The thiazide-sensitive Na+-Cl- cotransporter: molecular biology, functional properties, and regulation by WNKs. Am J Physiol Renal Physiol. 2009 Oct;297(4):F838-48. Epub 2009 May 27. Pubmed
  3. 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. Pubmed
  4. Ko B, Hoover RS: Molecular physiology of the thiazide-sensitive sodium-chloride cotransporter. Curr Opin Nephrol Hypertens. 2009 Sep;18(5):421-7. Pubmed

4. Solute carrier family 12 member 2

Pharmacological action: yes
Actions: inhibitor

Electrically silent transporter system. Mediates sodium and chloride reabsorption. Plays a vital role in the regulation of ionic balance and cell volume

Organism class: human
UniProt ID: P55011 Link_out
Gene: SLC12A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Duarte JD, Cooper-DeHoff RM: Mechanisms for blood pressure lowering and metabolic effects of thiazide and thiazide-like diuretics. Expert Rev Cardiovasc Ther. 2010 Jun;8(6):793-802. Pubmed
  2. Gamba G: The thiazide-sensitive Na+-Cl- cotransporter: molecular biology, functional properties, and regulation by WNKs. Am J Physiol Renal Physiol. 2009 Oct;297(4):F838-48. Epub 2009 May 27. Pubmed
  3. 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. Pubmed
  4. Ko B, Hoover RS: Molecular physiology of the thiazide-sensitive sodium-chloride cotransporter. Curr Opin Nephrol Hypertens. 2009 Sep;18(5):421-7. Pubmed

5. 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. Duarte JD, Cooper-DeHoff RM: Mechanisms for blood pressure lowering and metabolic effects of thiazide and thiazide-like diuretics. Expert Rev Cardiovasc Ther. 2010 Jun;8(6):793-802. Pubmed
  2. Gamba G: The thiazide-sensitive Na+-Cl- cotransporter: molecular biology, functional properties, and regulation by WNKs. Am J Physiol Renal Physiol. 2009 Oct;297(4):F838-48. Epub 2009 May 27. Pubmed
  3. 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. Pubmed
  4. Ko B, Hoover RS: Molecular physiology of the thiazide-sensitive sodium-chloride cotransporter. Curr Opin Nephrol Hypertens. 2009 Sep;18(5):421-7. Pubmed
Comments
Drug created on June 30, 2007 11:21 / Updated on November 10, 2010 13:47

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.