Quinethazone

Identification

Generic Name
Quinethazone
DrugBank Accession Number
DB01325
Background

Quinethazone, marketed as Hydromox, is a thiazide diuretic indicated for hypertension. Patients may experience adverse reactions such as dizziness, dry mouth, nausea, and hypokalemia.

Type
Small Molecule
Groups
Approved
Structure
Weight
Average: 289.739
Monoisotopic: 289.028789662
Chemical Formula
C10H12ClN3O3S
Synonyms
  • Chinetazone
  • Quinetazona
  • Quinethazon
  • Quinethazone
  • Quinethazonum
External IDs
  • CL 36010

Pharmacology

Indication

Used to treat hypertension.

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Contraindications & Blackbox Warnings
Prevent Adverse Drug Events Today
Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events with our Clinical API
Learn more
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
ASolute carrier family 12 member 1
inhibitor
Humans
ASolute carrier family 12 member 2
inhibitor
Humans
ASolute carrier family 12 member 3
inhibitor
Humans
ACarbonic anhydrase 1
inhibitor
Humans
ACarbonic anhydrase 2
inhibitor
Humans
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

Adverse Effects
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!
See the data
Improve decision support & research outcomes with our structured adverse effects data.
See a data sample
Toxicity

Not Available

Pathways
PathwayCategory
Quinethazone Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
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.
DrugInteraction
AbacavirQuinethazone may increase the excretion rate of Abacavir which could result in a lower serum level and potentially a reduction in efficacy.
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.
AcetaminophenQuinethazone may increase the excretion rate of Acetaminophen which could result in a lower serum level and potentially a reduction in efficacy.
Food Interactions
  • Take with food. Food increases bioavailability.

Products

Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
International/Other Brands
Aquamox / Hydromox / Idrokin

Categories

ATC Codes
G01AE10 — Combinations of sulfonamidesC03BA02 — QuinethazoneC03BB02 — Quinethazone and potassium
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
Amine / Amino acid or derivatives / Aminosulfonyl compound / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Benzenoid / Carboxamide group / Carboxylic acid derivative
show 20 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
quinazolines (CHEBI:8717)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
455E0S048W
CAS number
73-49-4
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

References

General References
Not Available
Human Metabolome Database
HMDB0015420
KEGG Drug
D00461
KEGG Compound
C07342
PubChem Compound
6307
PubChem Substance
46507280
ChemSpider
6068
BindingDB
25898
RxNav
59743
ChEBI
8717
ChEMBL
CHEMBL1532
Therapeutic Targets Database
DAP000955
PharmGKB
PA164760863
Wikipedia
Quinethazone

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Tablet
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-MSsplash10-0a4i-2390000000-828ade4d50b30315d546
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-01ox-1920000000-83ac1cb82abae8f21317
MS/MS Spectrum - , positiveLC-MS/MSsplash10-01ox-1920000000-83ac1cb82abae8f21317
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0006-0090000000-83291c0366d856dfc5e7
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-000i-0090000000-dc9ec36489f10df6b9c8
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0006-0090000000-5e5330b35660eb540534
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-000i-4090000000-509ae82988af3bc5e2bf
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-001u-0930000000-94b2ce65a988acf61ff6
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-9210000000-e6daf26c838cd770ea18
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-167.889006
predicted
DarkChem Lite v0.1.0
[M-H]-160.95576
predicted
DeepCCS 1.0 (2019)
[M+H]+168.487106
predicted
DarkChem Lite v0.1.0
[M+H]+163.31377
predicted
DeepCCS 1.0 (2019)
[M+Na]+168.004006
predicted
DarkChem Lite v0.1.0
[M+Na]+169.40692
predicted
DeepCCS 1.0 (2019)

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Kind
Protein
Organism
Humans
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
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
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Details
4. Carbonic anhydrase 1
Kind
Protein
Organism
Humans
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. [Article]
  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. [Article]
  3. Supuran CT: Diuretics: from classical carbonic anhydrase inhibitors to novel applications of the sulfonamides. Curr Pharm Des. 2008;14(7):641-8. [Article]
Details
5. Carbonic anhydrase 2
Kind
Protein
Organism
Humans
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. [Article]
  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. [Article]
  3. Supuran CT: Diuretics: from classical carbonic anhydrase inhibitors to novel applications of the sulfonamides. Curr Pharm Des. 2008;14(7):641-8. [Article]

Drug created at June 30, 2007 17:21 / Updated at February 21, 2021 18:51