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Identification
NameQuinethazone
Accession NumberDB01325
Typesmall molecule
Groupsapproved
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
Synonyms
SynonymLanguageCode
ChinetazoneNot AvailableDCIT
ChinethazonumNot AvailableNot Available
HydromoxNot AvailableNot Available
QuinetazonaSpanishINN
QuinethazonNot AvailableNot Available
QuinethazonumLatinINN
SaltsNot Available
Brand names
NameCompany
AquamoxNot Available
HydromoxNot Available
IdrokinNot Available
Brand mixtures
Brand NameIngredients
Hydromox RQuinethazone + Reserpine
Categories
CAS number73-49-4
WeightAverage: 289.739
Monoisotopic: 289.028789662
Chemical FormulaC10H12ClN3O3S
InChI KeyAGMMTXLNIQSRCG-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)
IUPAC Name
7-chloro-2-ethyl-4-oxo-1,2,3,4-tetrahydroquinazoline-6-sulfonamide
SMILES
CCC1NC(=O)C2=CC(=C(Cl)C=C2N1)S(N)(=O)=O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassNaphthyridines
SubclassQuinazolines
Direct parentQuinazolines
Alternative parentsBenzenesulfonamides; Chlorobenzenes; Aryl Chlorides; Sulfonyls; Sulfonamides; Secondary Carboxylic Acid Amides; Secondary Amines; Carboxylic Acids; Polyamines; Organochlorides
Substituentschlorobenzene; aryl halide; aryl chloride; benzene; sulfonamide; sulfonyl; sulfonic acid derivative; secondary carboxylic acid amide; carboxamide group; secondary amine; polyamine; carboxylic acid derivative; carboxylic acid; amine; organohalogen; organochloride; organonitrogen compound
Classification descriptionThis compound belongs to the quinazolines. These are compounds containing a quinazoline moiety, which is made up of two fused six-member aromatic rings, a benzene ring and a pyrimidine ring.
Pharmacology
IndicationUsed to treat hypertension.
PharmacodynamicsQuinethazone 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 actionAs 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.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Quinethazone Action PathwayDrug actionSMP00091
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9952
Blood Brain Barrier - 0.7026
Caco-2 permeable - 0.7327
P-glycoprotein substrate Non-substrate 0.5421
P-glycoprotein inhibitor I Non-inhibitor 0.847
P-glycoprotein inhibitor II Non-inhibitor 0.9619
Renal organic cation transporter Non-inhibitor 0.8991
CYP450 2C9 substrate Non-substrate 0.5767
CYP450 2D6 substrate Non-substrate 0.8418
CYP450 3A4 substrate Non-substrate 0.6226
CYP450 1A2 substrate Non-inhibitor 0.9045
CYP450 2C9 substrate Non-inhibitor 0.9071
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Non-inhibitor 0.9025
CYP450 3A4 substrate Non-inhibitor 0.9011
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6867
Ames test Non AMES toxic 0.9133
Carcinogenicity Non-carcinogens 0.7634
Biodegradation Not ready biodegradable 1.0
Rat acute toxicity 1.8960 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9882
hERG inhibition (predictor II) Non-inhibitor 0.9334
Pharmacoeconomics
Manufacturers
  • Lederle laboratories div american cyanamid co
PackagersNot Available
Dosage forms
FormRouteStrength
TabletOral
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point251 °CPhysProp
water solubility150 mg/L (at 25 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
Predicted Properties
PropertyValueSource
water solubility2.51e+00 g/lALOGPS
logP1.6ALOGPS
logP1.19ChemAxon
logS-2.1ALOGPS
pKa (strongest acidic)9.56ChemAxon
pKa (strongest basic)-0.97ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count4ChemAxon
hydrogen donor count3ChemAxon
polar surface area101.29ChemAxon
rotatable bond count2ChemAxon
refractivity69.34ChemAxon
polarizability27.3ChemAxon
number of rings2ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD00461
KEGG CompoundC07342
PubChem Compound6307
PubChem Substance46507280
ChemSpider6068
BindingDB25898
Therapeutic Targets DatabaseDAP000955
PharmGKBPA164760863
WikipediaQuinethazone
ATC CodesC03BA02
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
DigoxinPossible electrolyte variations and arrhythmias
LithiumThe thiazide diuretic, quinethazone, may increase serum levels of lithium.
Food Interactions
  • Take with food to increase bioavailability.

Targets

1. Carbonic anhydrase 1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Carbonic anhydrase 1 P00915 Details

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

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Carbonic anhydrase 2 P00918 Details

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

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 12 member 1 Q13621 Details

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

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 12 member 2 P55011 Details

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

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 12 member 3 P55017 Details

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

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Drug created on June 30, 2007 11:21 / Updated on September 16, 2013 17:14