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Chlorothiazide

July 24, 2017
Common Name

Chlorothiazide Description

Chlorothiazide 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 tublie via the Na-Cl cotransporter, resliting in an increase in the excretion of sodium, chloride, and water. Thiazides like chlorothiazide also inhibit sodium ion transport across the renal tubliar epithelium through binding to the thiazide sensitive sodium-chloride transporter. This reslits 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

MOLSDF3D-SDFPDBSMILESInChI View 3D Structure

Synonyms

Value Source 6-chloro-1,1-dioxo-1,2-dihydro-1Lambda*6*-benzo[1,2,4]thiadiazine-7-slifonic acid amideChEBI 6-chloro-7-Slifamoyl-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-slifonate amideGenerator 6-chloro-1,1-dioxo-1,2-dihydro-1Lambda*6*-benzo[1,2,4]thiadiazine-7-sliphonate amideGenerator 6-chloro-1,1-dioxo-1,2-dihydro-1Lambda*6*-benzo[1,2,4]thiadiazine-7-sliphonic acid amideGenerator 6-chloro-7-Sliphamoyl-2H-1,2,4-benzothiadiazine 1,1-dioxideGenerator ChlorothiazidHMDB ChlorthiazideHMDB ChlortiazidHMDB

Chemical Formlia

C7H6ClN3O4S2 Average Molecliar Weight

295.723 Monoisotopic Molecliar Weight

294.948824782 IUPAC Name

6-chloro-1,1-dioxo-4H-1λ⁶,2,4-benzothiadiazine-7-slifonamide Traditional Name

microzide CAS Registry Number

58-94-6 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 Key

JBMKAUGHUNFTOL-UHFFFAOYSA-N Chemical Taxonomy Description

This 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. Kingdom

Chemical entities Super Class

Organic compounds Class

Organoheterocyclic compounds Sub Class

Thiadiazines Direct Parent

1,2,4-benzothiadiazine-1,1-dioxides Alternative Parents

  • Organoslifonamides
  • Benzenoids
  • Aryl chlorides
  • Aminoslifonyl compounds
  • Propargyl-type 1,3-dipolar organic compounds
  • Formamidines
  • Azacyclic compounds
  • Organopnictogen compounds
  • Organochlorides
  • Organic oxides
  • Hydrocarbon derivatives

    • Substituents

  • 1,2,4-benzothiadiazine-1,1-dioxide
  • Aryl chloride
  • Aryl halide
  • Organoslifonic acid amide
  • Benzenoid
  • Organic slifonic acid or derivatives
  • Organoslifonic acid or derivatives
  • Slifonyl
  • Aminoslifonyl compound
  • Propargyl-type 1,3-dipolar organic compound
  • Formamidine
  • Amidine
  • Organic 1,3-dipolar compound
  • Azacycle
  • Organopnictogen compound
  • Organic nitrogen compound
  • Organic oxygen compound
  • Organoslifur compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Aromatic heteropolycyclic compound

    • Molecliar Framework

    Aromatic heteropolycyclic compounds External Descriptors

  • benzothiadiazine (CHEBI:3640 )

    • Ontology Status

    Expected but not Quantified Origin

  • Drug

    • Biofunction

  • Antihypertensive Agents
  • Diuretics
  • Diuretics, Thiazide
  • Sodium Chloride Symporter Inhibitors

    • Application

  • Pharmaceutical

    • Cellliar locations

  • Cytoplasm
  • Membrane

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting Point350 °CNot Available Boiling PointNot AvailableNot Available Water Solubility3.98e-01 g/LNot Available LogP-0.5Not Available

    Predicted Properties

    Property Value Source 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 Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

    Spectra Spectra

    Spectrum Type Description Splash Key LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , negativesplash10-0006-0090000000-e74dd6446e0284a7f0aaView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , negativesplash10-0006-0090000000-baf93e639a13c39dc1d6View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , negativesplash10-01ox-0090000000-473477518be3f6c8ddcdView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , negativesplash10-03di-0290000000-0e599c26917ade291ca0View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , negativesplash10-03di-0890000000-ad270ef1247ce9a114adView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , negativesplash10-004i-0920000000-3c4bb920bb8316022718View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , negativesplash10-004i-2900000000-eca13dbca70054de3470View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , negativesplash10-02vr-9700000000-9261e1bf4e212aee7d84View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , negativesplash10-0i09-9100000000-491baf01fc6ef9ca39e1View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-0002-0090000000-388cb4ff11dc0a41ad99View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-002b-0090000000-5645eee512f78cd689a7View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-0udi-0390000000-a39ffe78224ed4cacc13View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-0pbl-0920000000-eb979e3c4ecd1f12fb71View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-059f-2900000000-4c2eb27958fba0102431View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-05tk-5900000000-b42b446bc2b9f6216af1View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-00kk-9400000000-b4b975e3c1fabe09f4a7View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-03di-9100000000-f8f80586b12a43c2a667View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-03di-9000000000-9d41a0f061f998097c17View in MoNA Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, NegativeNot Available

    Biological Properties Cellliar Locations

  • Cytoplasm
  • Membrane

    • Biofluid Locations

  • Blood
  • Urine

    • Tissue Location

    Not Available Pathways

    Name SMPDB Link KEGG Link Chlorothiazide PathwaySMP00078Not Available

    Normal Concentrations

    Biofluid Status Value Age Sex Condition Reference Details BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00880

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00880

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Associated Disorders and Diseases Disease References

    None Associated OMIM IDs

    None External Links DrugBank ID

    DB00880 DrugBank Metabolite ID

    Not Available Phenol Explorer Compound ID

    Not Available Phenol Explorer Metabolite ID

    Not Available FoodDB ID

    Not Available KNApSAcK ID

    Not Available Chemspider ID

    2619 KEGG Compound ID

    C07461 BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Chlorothiazide NuGOwiki Link

    HMDB15018 Metagene Link

    HMDB15018 METLIN ID

    Not Available PubChem Compound

    2720 PDB ID

    Not Available ChEBI ID

    3640

    Product: N7-Methyladenosine

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References Not 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 Dents disease and Bartters 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 Gitelmans 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 Gitelmans 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 ]

    PMID: 27966610

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