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
Synonyms
  • Chinetazone
  • Chinethazonum
  • Hydromox
  • Quinetazona
  • Quinethazon
  • Quinethazonum
International/Other Brands
Aquamox / Hydromox / Idrokin
Categories
UNII
455E0S048W
CAS number
73-49-4
Weight
Average: 289.739
Monoisotopic: 289.028789662
Chemical Formula
C10H12ClN3O3S
InChI Key
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)
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

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.

TargetActionsOrganism
ACarbonic anhydrase 1
inhibitor
Human
ACarbonic anhydrase 2
inhibitor
Human
ASolute carrier family 12 member 1
inhibitor
Human
ASolute carrier family 12 member 2
inhibitor
Human
ASolute carrier family 12 member 3
inhibitor
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Quinethazone Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic AcidThe risk or severity of hypotension can be increased when Quinethazone is combined with 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid.
1alpha-Hydroxyvitamin D5The risk or severity of hypercalcemia can be increased when Quinethazone is combined with 1alpha-Hydroxyvitamin D5.
2,4-thiazolidinedioneThe therapeutic efficacy of 2,4-thiazolidinedione can be decreased when used in combination with Quinethazone.
AbediterolAbediterol may increase the hypokalemic activities of Quinethazone.
AcarboseThe therapeutic efficacy of Acarbose can be decreased when used in combination with Quinethazone.
AceclofenacThe therapeutic efficacy of Quinethazone can be decreased when used in combination with Aceclofenac.
AcemetacinThe therapeutic efficacy of Quinethazone can be decreased when used in combination with Acemetacin.
AcetohexamideThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Quinethazone.
AcetyldigitoxinThe risk or severity of adverse effects can be increased when Quinethazone is combined with Acetyldigitoxin.
AcetyldigoxinThe risk or severity of adverse effects can be increased when Quinethazone is combined with Acetyldigoxin.
Food Interactions
  • Take with food to increase bioavailability.

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0015420
KEGG Drug
D00461
KEGG Compound
C07342
PubChem Compound
6307
PubChem Substance
46507280
ChemSpider
6068
BindingDB
25898
ChEBI
8717
ChEMBL
CHEMBL1532
Therapeutic Targets Database
DAP000955
PharmGKB
PA164760863
Wikipedia
Quinethazone
ATC Codes
C03BA02 — QuinethazoneG01AE10 — Combinations of sulfonamidesC03BB02 — Quinethazone and potassium

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)251 °CPhysProp
water solubility150 mg/L (at 25 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
Predicted Properties
PropertyValueSource
Water Solubility2.51 mg/mLALOGPS
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 Area101.29 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity69.34 m3·mol-1ChemAxon
Polarizability27.3 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9952
Blood Brain Barrier-0.7026
Caco-2 permeable-0.7327
P-glycoprotein substrateNon-substrate0.5421
P-glycoprotein inhibitor INon-inhibitor0.847
P-glycoprotein inhibitor IINon-inhibitor0.9619
Renal organic cation transporterNon-inhibitor0.8991
CYP450 2C9 substrateNon-substrate0.5767
CYP450 2D6 substrateNon-substrate0.8418
CYP450 3A4 substrateNon-substrate0.6226
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.9011
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6867
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.7634
BiodegradationNot ready biodegradable1.0
Rat acute toxicity1.8960 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9882
hERG inhibition (predictor II)Non-inhibitor0.9334
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-01ox-1920000000-83ac1cb82abae8f21317

Taxonomy

Description
This compound belongs to the class of organic compounds known as 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazanaphthalenes
Sub Class
Benzodiazines
Direct Parent
Quinazolines
Alternative Parents
Secondary alkylarylamines / Organosulfonamides / Benzenoids / Aryl chlorides / Vinylogous amides / Aminosulfonyl compounds / Secondary carboxylic acid amides / Lactams / Amino acids and derivatives / Azacyclic compounds
show 5 more
Substituents
Quinazoline / Secondary aliphatic/aromatic amine / Aryl chloride / Aryl halide / Benzenoid / Organosulfonic acid amide / Organic sulfonic acid or derivatives / Organosulfonic acid or derivatives / Vinylogous amide / Aminosulfonyl compound
show 20 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
quinazolines (CHEBI:8717)

Targets

Details
1. Carbonic anhydrase 1
Kind
Protein
Organism
Human
Pharmacological action
Yes
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
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. doi: 10.1039/b800767e. Epub 2008 May 29. [PubMed:18600270]
  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. doi: 10.1016/j.bmcl.2008.03.051. Epub 2008 Mar 20. [PubMed:18374572]
  3. Supuran CT: Diuretics: from classical carbonic anhydrase inhibitors to novel applications of the sulfonamides. Curr Pharm Des. 2008;14(7):641-8. [PubMed:18336309]
Details
2. Carbonic anhydrase 2
Kind
Protein
Organism
Human
Pharmacological action
Yes
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
  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. doi: 10.1039/b800767e. Epub 2008 May 29. [PubMed:18600270]
  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. doi: 10.1016/j.bmcl.2008.03.051. Epub 2008 Mar 20. [PubMed:18374572]
  3. Supuran CT: Diuretics: from classical carbonic anhydrase inhibitors to novel applications of the sulfonamides. Curr Pharm Des. 2008;14(7):641-8. [PubMed:18336309]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Sodium:potassium:chloride symporter activity
Specific Function
Electrically silent transporter system. Mediates sodium and chloride reabsorption. Plays a vital role in the regulation of ionic balance and cell volume.
Gene Name
SLC12A1
Uniprot ID
Q13621
Uniprot Name
Solute carrier family 12 member 1
Molecular Weight
121449.13 Da
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. doi: 10.1586/erc.10.27. [PubMed:20528637]
  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. doi: 10.1152/ajprenal.00159.2009. Epub 2009 May 27. [PubMed:19474192]
  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:12538756]
  4. Ko B, Hoover RS: Molecular physiology of the thiazide-sensitive sodium-chloride cotransporter. Curr Opin Nephrol Hypertens. 2009 Sep;18(5):421-7. doi: 10.1097/MNH.0b013e32832f2fcb. [PubMed:19636250]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Sodium:potassium:chloride symporter activity
Specific Function
Electrically silent transporter system. Mediates sodium and chloride reabsorption. Plays a vital role in the regulation of ionic balance and cell volume.
Gene Name
SLC12A2
Uniprot ID
P55011
Uniprot Name
Solute carrier family 12 member 2
Molecular Weight
131445.825 Da
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. doi: 10.1586/erc.10.27. [PubMed:20528637]
  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. doi: 10.1152/ajprenal.00159.2009. Epub 2009 May 27. [PubMed:19474192]
  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:12538756]
  4. Ko B, Hoover RS: Molecular physiology of the thiazide-sensitive sodium-chloride cotransporter. Curr Opin Nephrol Hypertens. 2009 Sep;18(5):421-7. doi: 10.1097/MNH.0b013e32832f2fcb. [PubMed:19636250]
Kind
Protein
Organism
Human
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
  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. doi: 10.1586/erc.10.27. [PubMed:20528637]
  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. doi: 10.1152/ajprenal.00159.2009. Epub 2009 May 27. [PubMed:19474192]
  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:12538756]
  4. Ko B, Hoover RS: Molecular physiology of the thiazide-sensitive sodium-chloride cotransporter. Curr Opin Nephrol Hypertens. 2009 Sep;18(5):421-7. doi: 10.1097/MNH.0b013e32832f2fcb. [PubMed:19636250]

Drug created on June 30, 2007 11:21 / Updated on November 02, 2018 04:59