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Record Information
Version4.0
Creation Date2012-09-06 15:16:51 UTC
Update Date2017-09-22 02:31:25 UTC
HMDB IDHMDB0015018
Secondary Accession Numbers
  • HMDB15018
Metabolite Identification
Common NameChlorothiazide
DescriptionChlorothiazide is only found in individuals that have used or taken this drug. It is a thiazide diuretic with actions and uses similar to those of hydrochlorothiazide. (From Martindale, The Extra Pharmacopoeia, 30th ed, p812)As a diuretic, chlorothiazide 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 chlorothiazide 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 chlorothiazide 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.
Structure
Thumb
Synonyms
ValueSource
6-chloro-1,1-dioxo-1,2-dihydro-1Lambda*6*-benzo[1,2,4]thiadiazine-7-sulfonic acid amideChEBI
6-chloro-7-Sulfamoyl-2H-1,2,4-benzothiadiazine 1,1-dioxideChEBI
ChlorothiazidumChEBI
ClorotiazidaChEBI
6-chloro-1,1-dioxo-1,2-dihydro-1Lambda*6*-benzo[1,2,4]thiadiazine-7-sulfonate amideGenerator
6-chloro-1,1-dioxo-1,2-dihydro-1Lambda*6*-benzo[1,2,4]thiadiazine-7-sulphonate amideGenerator
6-chloro-1,1-dioxo-1,2-dihydro-1Lambda*6*-benzo[1,2,4]thiadiazine-7-sulphonic acid amideGenerator
6-chloro-7-Sulphamoyl-2H-1,2,4-benzothiadiazine 1,1-dioxideGenerator
ChlorothiazidHMDB
ChlorthiazideHMDB
ChlortiazidHMDB
Chemical FormulaC7H6ClN3O4S2
Average Molecular Weight295.723
Monoisotopic Molecular Weight294.948824782
IUPAC Name6-chloro-1,1-dioxo-4H-1λ⁶,2,4-benzothiadiazine-7-sulfonamide
Traditional Namemicrozide
CAS Registry Number58-94-6
SMILES
NS(=O)(=O)C1=C(Cl)C=C2NC=NS(=O)(=O)C2=C1
InChI Identifier
InChI=1S/C7H6ClN3O4S2/c8-4-1-5-7(2-6(4)16(9,12)13)17(14,15)11-3-10-5/h1-3H,(H,10,11)(H2,9,12,13)
InChI KeyJBMKAUGHUNFTOL-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of chemical entities 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.
KingdomChemical entities
Super ClassOrganic compounds
ClassOrganoheterocyclic compounds
Sub ClassThiadiazines
Direct Parent1,2,4-benzothiadiazine-1,1-dioxides
Alternative Parents
Substituents
  • 1,2,4-benzothiadiazine-1,1-dioxide
  • Aryl chloride
  • Aryl halide
  • Organosulfonic acid amide
  • Benzenoid
  • Organic sulfonic acid or derivatives
  • Organosulfonic acid or derivatives
  • Sulfonyl
  • Aminosulfonyl compound
  • Propargyl-type 1,3-dipolar organic compound
  • Formamidine
  • Amidine
  • Organic 1,3-dipolar compound
  • Azacycle
  • Organopnictogen compound
  • Organic nitrogen compound
  • Organic oxygen compound
  • Organosulfur compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
StatusExpected but not Quantified
Origin
  • Drug
Biofunction
  • Antihypertensive Agents
  • Diuretics
  • Diuretics, Thiazide
  • Sodium Chloride Symporter Inhibitors
Application
  • Pharmaceutical
Cellular locations
  • Cytoplasm
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point350 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility3.98e-01 g/LNot Available
LogP-0.5Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.4 mg/mLALOGPS
logP0.41ALOGPS
logP-0.44ChemAxon
logS-2.9ALOGPS
pKa (Strongest Acidic)9.1ChemAxon
pKa (Strongest Basic)1.15ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area118.69 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity62.51 m3·mol-1ChemAxon
Polarizability24.55 Å3ChemAxon
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-MSNot Available
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0006-0090000000-e74dd6446e0284a7f0aaView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0006-0090000000-baf93e639a13c39dc1d6View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-01ox-0090000000-473477518be3f6c8ddcdView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-03di-0290000000-0e599c26917ade291ca0View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-03di-0890000000-ad270ef1247ce9a114adView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-004i-0920000000-3c4bb920bb8316022718View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-004i-2900000000-eca13dbca70054de3470View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-02vr-9700000000-9261e1bf4e212aee7d84View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0i09-9100000000-491baf01fc6ef9ca39e1View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0002-0090000000-388cb4ff11dc0a41ad99View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-002b-0090000000-5645eee512f78cd689a7View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0udi-0390000000-a39ffe78224ed4cacc13View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0pbl-0920000000-eb979e3c4ecd1f12fb71View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-059f-2900000000-4c2eb27958fba0102431View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-05tk-5900000000-b42b446bc2b9f6216af1View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-00kk-9400000000-b4b975e3c1fabe09f4a7View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-03di-9100000000-f8f80586b12a43c2a667View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-03di-9000000000-9d41a0f061f998097c17View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Biological Properties
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
Pathways
NameSMPDB/PathwhizKEGG
Chlorothiazide PathwayPw000325Pw000325 greyscalePw000325 simpleNot Available
Displaying 1 entry
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00880 details
UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00880 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00880
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID2619
KEGG Compound IDC07461
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkChlorothiazide
NuGOwiki LinkHMDB0015018
METLIN IDNot Available
PubChem Compound2720
PDB IDNot Available
ChEBI ID3640
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General ReferencesNot Available

Enzymes

General function:
Involved in carbonate dehydratase activity
Specific function:
Reversible hydration of carbon dioxide. Can hydrates cyanamide to urea.
Gene Name:
CA1
Uniprot ID:
P00915
Molecular weight:
28870.0
References
  1. Puscas I, Coltau M, Baican M, Domuta G, Hecht A: Vasodilatory effect of diuretics is dependent on inhibition of vascular smooth muscle carbonic anhydrase by a direct mechanism of action. Drugs Exp Clin Res. 1999;25(6):271-9. [PubMed:10713865 ]
  2. Puscas I, Coltau M, Baican M, Pasca R, Domuta G: The inhibitory effect of diuretics on carbonic anhydrases. Res Commun Mol Pathol Pharmacol. 1999;105(3):213-36. [PubMed:10954127 ]
General function:
Involved in carbonate dehydratase activity
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 into the anterior chamber of the eye.
Gene Name:
CA2
Uniprot ID:
P00918
Molecular weight:
29245.895
References
  1. Weiner ID, Verlander JW: Renal and hepatic expression of the ammonium transporter proteins, Rh B Glycoprotein and Rh C Glycoprotein. Acta Physiol Scand. 2003 Dec;179(4):331-8. [PubMed:14656370 ]
  2. Puscas I, Coltau M, Baican M, Pasca R, Domuta G: The inhibitory effect of diuretics on carbonic anhydrases. Res Commun Mol Pathol Pharmacol. 1999;105(3):213-36. [PubMed:10954127 ]
  3. Verlander JW, Miller RT, Frank AE, Royaux IE, Kim YH, Weiner ID: Localization of the ammonium transporter proteins RhBG and RhCG in mouse kidney. Am J Physiol Renal Physiol. 2003 Feb;284(2):F323-37. Epub 2002 Oct 8. [PubMed:12388412 ]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
General function:
Involved in transport
Specific function:
Electrically silent transporter system. Mediates sodium and chloride reabsorption
Gene Name:
SLC12A3
Uniprot ID:
P55017
Molecular weight:
113124.0
References
  1. Thakker RV: Molecular pathology of renal chloride channels in Dent's disease and Bartter's syndrome. Exp Nephrol. 2000 Nov-Dec;8(6):351-60. [PubMed:11014932 ]
  2. Schmidt H, Kabesch M, Schwarz HP, Kiess W: Clinical, biochemical and molecular genetic data in five children with Gitelman's syndrome. Horm Metab Res. 2001 Jun;33(6):354-7. [PubMed:11456284 ]
  3. Wilson FH, Kahle KT, Sabath E, Lalioti MD, Rapson AK, Hoover RS, Hebert SC, Gamba G, Lifton RP: Molecular pathogenesis of inherited hypertension with hyperkalemia: the Na-Cl cotransporter is inhibited by wild-type but not mutant WNK4. Proc Natl Acad Sci U S A. 2003 Jan 21;100(2):680-4. Epub 2003 Jan 6. [PubMed:12515852 ]
  4. Maki N, Komatsuda A, Wakui H, Ohtani H, Kigawa A, Aiba N, Hamai K, Motegi M, Yamaguchi A, Imai H, Sawada K: Four novel mutations in the thiazide-sensitive Na-Cl co-transporter gene in Japanese patients with Gitelman's syndrome. Nephrol Dial Transplant. 2004 Jul;19(7):1761-6. Epub 2004 Apr 6. [PubMed:15069170 ]
  5. Reinalter SC, Jeck N, Peters M, Seyberth HW: Pharmacotyping of hypokalaemic salt-losing tubular disorders. Acta Physiol Scand. 2004 Aug;181(4):513-21. [PubMed:15283765 ]
General function:
Involved in carbonate dehydratase activity
Specific function:
Reversible hydration of carbon dioxide. May stimulate the sodium/bicarbonate transporter activity of SLC4A4 that acts in pH homeostasis. It is essential for acid overload removal from the retina and retina epithelium, and acid release in the choriocapillaris in the choroid.
Gene Name:
CA4
Uniprot ID:
P22748
Molecular weight:
35032.075
References
  1. Puscas I, Coltau M, Baican M, Domuta G, Hecht A: Vasodilatory effect of diuretics is dependent on inhibition of vascular smooth muscle carbonic anhydrase by a direct mechanism of action. Drugs Exp Clin Res. 1999;25(6):271-9. [PubMed:10713865 ]
  2. Puscas I, Coltau M, Baican M, Pasca R, Domuta G: The inhibitory effect of diuretics on carbonic anhydrases. Res Commun Mol Pathol Pharmacol. 1999;105(3):213-36. [PubMed:10954127 ]

Transporters

General function:
Involved in ion transmembrane transporter activity
Specific function:
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one molecule of endogenous dicarboxylic acid (glutarate, ketoglutarate, etc). Mediates the sodium-independent uptake of 2,3-dimercapto-1-propanesulfonic acid (DMPS). Mediates the sodium-independent uptake of p- aminohippurate (PAH), ochratoxin (OTA), acyclovir (ACV), 3'-azido- 3-'deoxythymidine (AZT), cimetidine (CMD), 2,4-dichloro- phenoxyacetate (2,4-D), hippurate (HA), indoleacetate (IA), indoxyl sulfate (IS) and 3-carboxy-4-methyl-5-propyl-2- furanpropionate (CMPF), cidofovir, adefovir, 9-(2- phosphonylmethoxyethyl) guanine (PMEG), 9-(2- phosphonylmethoxyethyl) diaminopurine (PMEDAP) and edaravone sulfate. PAH uptake is inhibited by p- chloromercuribenzenesulphonate (PCMBS), diethyl pyrocarbonate (DEPC), sulindac, diclofenac, carprofen, glutarate and okadaic acid. PAH uptake is inhibited by benzothiazolylcysteine (BTC), S-chlorotrifluoroethylcysteine (CTFC), cysteine S-conjugates S-dichlorovinylcysteine (DCVC), furosemide, steviol, phorbol 12-myristate 13-acetate (PMA), calcium ionophore A23187, benzylpenicillin, furosemide, indomethacin, bumetamide, losartan, probenecid, phenol red, urate, and alpha-ketoglutarate
Gene Name:
SLC22A6
Uniprot ID:
Q4U2R8
Molecular weight:
61815.8
References
  1. Uwai Y, Saito H, Hashimoto Y, Inui KI: Interaction and transport of thiazide diuretics, loop diuretics, and acetazolamide via rat renal organic anion transporter rOAT1. J Pharmacol Exp Ther. 2000 Oct;295(1):261-5. [PubMed:10991988 ]