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Record Information
Version1.0
Creation Date2014-09-11 05:16:19 UTC
Update Date2016-10-28 10:03:39 UTC
Accession NumberCHEM003738
Identification
Common NameHydrochlorothiazide
ClassSmall Molecule
DescriptionA thiazide diuretic often considered the prototypical member of this class. It reduces the reabsorption of electrolytes from the renal tubules. This results in increased excretion of water and electrolytes, including sodium, potassium, chloride, and magnesium. It has been used in the treatment of several disorders including edema, hypertension, diabetes insipidus, and hypoparathyroidism.
Contaminant Sources
  • FooDB Chemicals
  • HMDB Contaminants - Urine
  • IARC Carcinogens Group 2B
  • STOFF IDENT Compounds
  • Suspected Compounds
  • Suspected Compounds - Waste Water
  • Suspected Compounds – Schymanski Project
  • T3DB toxins
  • ToxCast & Tox21 Chemicals
Contaminant Type
  • Amide
  • Amine
  • Antihypertensive Agent
  • Diuretic
  • Drug
  • Food Toxin
  • Metabolite
  • Organic Compound
  • Organochloride
  • Sodium Chloride Symporter Inhibitor
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
ValueSource
EsidrixChEBI
HidroclorotiazidaChEBI
HydrochlorothiazidumChEBI
MicrozideKegg
3,4-DihydrochlorothiazideHMDB
AcureticHMDB
AldactazideHMDB
AldorilHMDB
ApresazideHMDB
AquarillsHMDB
AquariusHMDB
BremilHMDB
CaplarilHMDB
CapozideHMDB
ChlorosulthiadilHMDB
ChlorothiazideHMDB
Chlorsulfonamidodihydrobenzothiadiazine dioxideHMDB
ChlorzideHMDB
CidrexHMDB
DichlorosalHMDB
DichlotiazidHMDB
DichlotrideHMDB
DiclotrideHMDB
DihydrochlorothiazidHMDB
DihydrochlorothiazideHMDB
DihydrochlorothiazidumHMDB
DihydrochloruritHMDB
DihydrochloruriteHMDB
DihydroxychlorothiazidumHMDB
DiremaHMDB
DisalunilHMDB
DiurilHMDB
DrenolHMDB
DyazideHMDB
EsidrexHMDB
EsimilHMDB
FluvinHMDB
HCTZHMDB
HCZHMDB
HidrilHMDB
HidrochlortiazidHMDB
HidroronolHMDB
HidrotiazidaHMDB
HydrilHMDB
Hydro-aquilHMDB
Hydro-DHMDB
Hydro-diurilHMDB
Hydrochloro thiazideHMDB
HydrochlorothiazidHMDB
Hydrochlorothiazide intensolHMDB
HydrochlorthiazideHMDB
HydrodiureticHMDB
HydrodiurilHMDB
HydropresHMDB
HydrosaluricHMDB
HydrothideHMDB
HydrozideHMDB
HypothiazidHMDB
HypothiazideHMDB
HyzaarHMDB
IdrotiazideHMDB
InderideHMDB
IvauganHMDB
Jen-dirilHMDB
Lopressor HCTHMDB
Lotensin HCTHMDB
MaschittHMDB
MaxzideHMDB
MegadiurilHMDB
ModureticHMDB
NefrixHMDB
Neo-codemaHMDB
NeoflumenHMDB
NewtolideHMDB
OreticHMDB
PanurinHMDB
PrinzideHMDB
Ro-hydrazideHMDB
Ser-ap-esHMDB
ServithiazidHMDB
ThiareticHMDB
ThiureticHMDB
ThlareticHMDB
TimolideHMDB
UnipresHMDB
UrodiazinHMDB
VasereticHMDB
VetidrexHMDB
ZiacHMDB
ZideHMDB
SectrazideHMDB
DichlothiazideHMDB
Chemical FormulaC7H8ClN3O4S2
Average Molecular Mass297.739 g/mol
Monoisotopic Mass296.964 g/mol
CAS Registry Number58-93-5
IUPAC Name6-chloro-1,1-dioxo-3,4-dihydro-2H-1lambda6,2,4-benzothiadiazine-7-sulfonamide
Traditional Name6-chloro-1,1-dioxo-3,4-dihydro-2H-1lambda6,2,4-benzothiadiazine-7-sulfonamide
SMILESNS(=O)(=O)C1=C(Cl)C=C2NCNS(=O)(=O)C2=C1
InChI IdentifierInChI=1S/C7H8ClN3O4S2/c8-4-1-5-7(2-6(4)16(9,12)13)17(14,15)11-3-10-5/h1-2,10-11H,3H2,(H2,9,12,13)
InChI KeyJZUFKLXOESDKRF-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as 1,2,4-benzothiadiazine-1,1-dioxides. These are aromatic heterocyclic compounds containing a 1,2,4-benzothiadiazine ring system with two S=O bonds at the 1-position.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassThiadiazines
Sub ClassBenzothiadiazines
Direct Parent1,2,4-benzothiadiazine-1,1-dioxides
Alternative Parents
Substituents
  • 1,2,4-benzothiadiazine-1,1-dioxide
  • Secondary aliphatic/aromatic amine
  • Aryl chloride
  • Aryl halide
  • Organosulfonic acid amide
  • Benzenoid
  • Organic sulfonic acid or derivatives
  • Organosulfonic acid or derivatives
  • Aminosulfonyl compound
  • Sulfonyl
  • Secondary amine
  • Azacycle
  • Organic oxide
  • Amine
  • Organopnictogen compound
  • Organosulfur compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue Locations
  • Adipose Tissue
  • Kidney
  • Platelet
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point266-268°C
Boiling PointNot Available
Solubility722 mg/L (at 25°C)
Predicted Properties
PropertyValueSource
Water Solubility2.24 g/LALOGPS
logP-0.16ALOGPS
logP-0.58ChemAxon
logS-2.1ALOGPS
pKa (Strongest Acidic)9.09ChemAxon
pKa (Strongest Basic)-2.7ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area118.36 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity63.11 m³·mol⁻¹ChemAxon
Polarizability25.35 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MSsplash10-014i-1490000000-623736f34c52e89bbc88View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-052b-0090000000-aaa48e4702874457ae26View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-0r6r-0920000000-b129acf72e7dde12441eView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-0a4i-1900000000-67f803f38aed0bd12adeView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-001i-0490000000-86abfe4bae6e32f1189aView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-014i-0090000000-7906a6e4cfb51dce1396View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0002-0090000000-c44dbed5084dc5df03d8View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0002-0090000000-976dcb246a2272b22565View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0uxr-1090000000-16e563e592e4a566424dView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0fb9-9580000000-3c9227e3df8ed6dc9ae9View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-004i-9720000000-12525bfcb83ea1611970View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-004i-9200000000-df37b796b59f084b0229View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0002-0090000000-220666bc28231ad387e8View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0002-0090000000-f434c5d8ee94540ec0d2View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0uxr-1090000000-8a3c270e0fb285b26f15View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0fb9-9480000000-5f6c5ed1d291d71a0aaeView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-004i-9520000000-679def33e8239c1382f3View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-004i-9400000000-c9b80274d62fda64c531View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-014i-0090000000-0a962453b9e31eec3822View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-0002-0090000000-ac2b5d07eaacba87a181View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0002-0090000000-ebd02b17cc1bcbc24502View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-014j-1090000000-5e38ac3d2095cf748e87View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0udi-0930000000-7d03b4df6a4398a11962View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00kb-0090000000-7508f697b07f36ba3fedView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-004j-7190000000-6fe4cadaa6d8f344354eView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-004i-9000000000-0ed40c1b83b8f3d34e9fView in MoNA
MSMass Spectrum (Electron Ionization)splash10-00r2-6490000000-3f5d9320308b823c6489View in MoNA
1D NMR1H NMR SpectrumNot Available
1D NMR1H NMR SpectrumNot Available
1D NMR13C NMR SpectrumNot Available
2D NMR[1H,13C] 2D NMR SpectrumNot Available
Toxicity Profile
Route of Exposure50-60%
Mechanism of ToxicityHydrochlorothiazide, a thiazide diuretic, inhibits water reabsorption in the nephron by inhibiting the sodium-chloride symporter (SLC12A3) in the distal convoluted tubule, which is responsible for 5% of total sodium reabsorption. Normally, the sodium-chloride symporter transports sodium and chloride from the lumen into the epithelial cell lining the distal convoluted tubule. The energy for this is provided by a sodium gradient established by sodium-potassium ATPases on the basolateral membrane. Once sodium has entered the cell, it is transported out into the basolateral interstitium via the sodium-potassium ATPase, causing an increase in the osmolarity of the interstitium, thereby establishing an osmotic gradient for water reabsorption. By blocking the sodium-chloride symporter, hydrochlorothiazide effectively reduces the osmotic gradient and water reabsorption throughout the nephron.
MetabolismHydrochlorothiazide is not metabolized. Route of Elimination: Hydrochlorothiazide is not metabolized but is eliminated rapidly by the kidney. Hydrochlorothiazide crosses the placental but not the blood-brain barrier and is excreted in breast milk. Half Life: 5.6 and 14.8 hours
Toxicity ValuesThe oral LD50 of hydrochlorothiazide is greater than 10 g/kg in the mouse and rat.
Lethal DoseNot Available
Carcinogenicity (IARC Classification)2B, possibly carcinogenic to humans. (16)
Uses/SourcesFor the treatment of high blood pressure and management of edema.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsThe most common signs and symptoms observed are those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. If digitalis has also been administered, hypokalemia may accentuate cardiac arrhythmias.
TreatmentNot Available
Concentrations
StatusValueUnitSample LocationReference
Detected and Quantified1000ng/LBioggio,Lugano
Detected and Quantified1300ng/LBussigny-prés-Lausanne
Detected and Quantified1200ng/LHallau,Klettgau
Detected and Quantified1000ng/LThal,Altenrhein
Detected and Quantified2300ng/LUetendorf,Thun
Detected and Quantified1000ng/LVernier,Aïre
Detected and Quantified1900ng/LWinterthur
Detected and Quantified1400ng/LWerdhölzli,Zürich
Detected and Quantified1200ng/LSchönau,Zug
Detected and Quantified1100ng/LAffoltern,Zwillikon
DrugBank IDDB00999
HMDB IDHMDB0001928
FooDB IDFDB022745
Phenol Explorer IDNot Available
KNApSAcK IDNot Available
BiGG IDNot Available
BioCyc IDNot Available
METLIN ID3169
PDB IDNot Available
Wikipedia LinkHydrochlorothiazide
Chemspider ID3513
ChEBI ID5778
PubChem Compound ID3639
Kegg Compound IDC07041
YMDB IDNot Available
ECMDB IDNot Available
References
Synthesis Reference

Frederic J. Nugent, John K. C. Yen, “Process for preparing the combination products of triamterene and hydrochlorothiazide.” U.S. Patent US4804540, issued July, 1987.

MSDSLink
General References
1. Dimitriadis G, Tegos C, Golfinopoulou L, Roboti C, Raptis S: Furosemide-induced hyperglycaemia: the implication of glycolytic kinases. Horm Metab Res. 1993 Nov;25(11):557-9.
2. Vandenheuvel WJ, Gruber VF, Walker RW, Wolf FJ: GLC analysis of hydrochlorothiazide in blood and plasma. J Pharm Sci. 1975 Aug;64(8):1309-12.
3. Yamazaki M, Ito Y, Suzuka T, Yaginuma H, Itoh S, Kamada A, Orita Y, Nakahama H, Nakanishi T, Ando A: Biopharmaceutical studies of thiazide diuretics. II. High-performance liquid chromatographic method for determination of hydrochlorothiazide in plasma, urine, blood cells and bile. Chem Pharm Bull (Tokyo). 1984 Jun;32(6):2387-94.
4. Germano G, Sanguigni V, Pignatelli P, Caccese D, Lenti L, Ragazzo M, Lauro R, Violi F: Enhanced platelet release of superoxide anion in systemic hypertension: role of AT1 receptors. J Hypertens. 2004 Jun;22(6):1151-6.
5. Bernik MM, Heimann JC, Nakandakare ER, Cazita PM, Nunes VS, Rocha JC, Neves MQ, Quintao EC: Effects of hydrochlorothiazide and propranolol treatment on chylomicron metabolism in hypertensive objects. Can J Physiol Pharmacol. 2005 Jul;83(7):617-23.
6. Splendiani G, Condo S: [Diuretic therapy in heart failure]. G Ital Nefrol. 2006 Jan-Feb;23 Suppl 34:S74-6.
7. Dornhorst A, Powell SH, Pensky J: Aggravation by propranolol of hyperglycaemic effect of hydrochlorothiazide in type II diabetics without alteration of insulin secretion. Lancet. 1985 Jan 19;1(8421):123-6.
8. Serradeil-Le Gal C, Lacour C, Valette G, Garcia G, Foulon L, Galindo G, Bankir L, Pouzet B, Guillon G, Barberis C, Chicot D, Jard S, Vilain P, Garcia C, Marty E, Raufaste D, Brossard G, Nisato D, Maffrand JP, Le Fur G: Characterization of SR 121463A, a highly potent and selective, orally active vasopressin V2 receptor antagonist. J Clin Invest. 1996 Dec 15;98(12):2729-38.
9. Kuo BS, Mandagere A, Osborne DR, Hwang KK: Column-switching high-performance liquid chromatographic (HPLC) determination of hydrochlorothiazide in rat, dog, and human plasma. Pharm Res. 1990 Dec;7(12):1257-61.
10. Cubeddu LX, Hoffmann IS, Davila S, Escontrelas C, Morales C, Rios A: Effects of propranolol, clonidine and hydrochlorothiazide treatment and abrupt discontinuation on central and peripheral noradrenergic activity in essential hypertension. Life Sci. 1986 Dec 22;39(25):2463-74.
11. Angelin B: Effect of thiazide treatment on biliary lipid composition in healthy volunteers. Eur J Clin Pharmacol. 1989;37(1):95-6.
12. Buttar HS: An overview of the influence of ACE inhibitors on fetal-placental circulation and perinatal development. Mol Cell Biochem. 1997 Nov;176(1-2):61-71.
13. Tisdall PA, Moyer TP, Anhalt JP: Liquid-chromatographic detection of thiazide diuretics in urine. Clin Chem. 1980 May;26(6):702-6.
14. Beermann B, Fahraeus L, Groschinsky-Grind M, Lindstrom B: Placental transfer of hydrochlorothiazide. Gynecol Obstet Invest. 1980;11(1):45-8.
15. Vonaparti A, Kazanis M, Panderi I: Development and validation of a liquid chromatographic/electrospray ionization mass spectrometric method for the determination of benazepril, benazeprilat and hydrochlorothiazide in human plasma. J Mass Spectrom. 2006 May;41(5):593-605.
16. https://www.ncbi.nlm.nih.gov/pubmed/?term=24055851
17. https://www.ncbi.nlm.nih.gov/pubmed/?term=24657333
18. https://www.ncbi.nlm.nih.gov/pubmed/?term=24849193