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Record Information
Version4.0
Creation Date2012-09-06 15:16:49 UTC
Update Date2017-09-27 08:27:37 UTC
HMDB IDHMDB0014580
Secondary Accession Numbers
  • HMDB14580
Metabolite Identification
Common NameBendroflumethiazide
DescriptionBendroflumethiazide 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. It has been used in the treatment of familial hyperkalemia, hypertension, edema, and urinary tract disorders. (From Martindale, The Extra Pharmacopoeia, 30th ed, p810)As a diuretic, bendroflumethiazide 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 bendroflumethiazide 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 bendroflumethiazide 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
+--3-Benzyl-3,4-dihydro-6-(trifluoromethyl)-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxideChEBI
6-Trifluoromethyl-3-benzyl-7-sulfamyl-3,4-dihydro-1,2,4-benzothiadiazine 1,1-dioxideChEBI
BendrofluazideChEBI
BendroflumethiazidumChEBI
BendroflumetiazidaChEBI
BenzhydroflumethiazideChEBI
+--3-Benzyl-3,4-dihydro-6-(trifluoromethyl)-2H-1,2,4-benzothiadiazine-7-sulphonamide 1,1-dioxideGenerator
6-Trifluoromethyl-3-benzyl-7-sulphamyl-3,4-dihydro-1,2,4-benzothiadiazine 1,1-dioxideGenerator
BendroflumethazideHMDB
BendrofumethiazideHMDB
BenzydroflumethiazideHMDB
BenzylhydroflumethiazideHMDB
BHFTHMDB
Bendroflumethiazide apothecon brandMeSH
Bristol-myers squibb brand OF bendroflumethiazideMeSH
DDSA brand OF bendroflumethiazideMeSH
EsberizidMeSH
NaturineMeSH
NeoNaClexMeSH
Schaper and brümmer brand OF bendroflumethiazideMeSH
Bendroflumethiazide berk brandMeSH
Bendroflumethiazide ddsa brandMeSH
Bendroflumethiazide goldshield brandMeSH
Bendroflumethiazide leo brandMeSH
Bristol myers squibb brand OF bendroflumethiazideMeSH
UrizidMeSH
AprinoxMeSH
Bendroflumethiazide protea brandMeSH
BenzideMeSH
BenzideMMeSH
BerkozideMeSH
leo Brand OF bendroflumethiazideMeSH
neo NaClexMeSH
Protea brand OF bendroflumethiazideMeSH
Apothecon brand OF bendroflumethiazideMeSH
Bendroflumethiazide knoll brandMeSH
Benzide mMeSH
Benzide-mMeSH
Berk brand OF bendroflumethiazideMeSH
CentylMeSH
Goldshield brand OF bendroflumethiazideMeSH
Knoll brand OF bendroflumethiazideMeSH
NaturetinMeSH
neo-NaClexMeSH
PlurylMeSH
Chemical FormulaC15H14F3N3O4S2
Average Molecular Weight421.415
Monoisotopic Molecular Weight421.037781946
IUPAC Name3-benzyl-1,1-dioxo-6-(trifluoromethyl)-3,4-dihydro-2H-1λ⁶,2,4-benzothiadiazine-7-sulfonamide
Traditional Namebendroflumethiazide
CAS Registry Number73-48-3
SMILES
NS(=O)(=O)C1=CC2=C(NC(CC3=CC=CC=C3)NS2(=O)=O)C=C1C(F)(F)F
InChI Identifier
InChI=1S/C15H14F3N3O4S2/c16-15(17,18)10-7-11-13(8-12(10)26(19,22)23)27(24,25)21-14(20-11)6-9-4-2-1-3-5-9/h1-5,7-8,14,20-21H,6H2,(H2,19,22,23)
InChI KeyHDWIHXWEUNVBIY-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
  • Secondary aliphatic/aromatic amine
  • Monocyclic benzene moiety
  • Organosulfonic acid amide
  • Benzenoid
  • Organic sulfonic acid or derivatives
  • Organosulfonic acid or derivatives
  • Aminosulfonyl compound
  • Sulfonyl
  • Azacycle
  • Alkyl fluoride
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Organic oxygen compound
  • Organosulfur compound
  • Organonitrogen compound
  • Organofluoride
  • Organohalogen compound
  • Organic nitrogen compound
  • Alkyl halide
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
Disposition

Biological Location:

  Subcellular:

  Biofluid and excreta:

Process

Naturally occurring process:

  Biological process:

    Biochemical pathway:

Role

Industrial application:

  Pharmaceutical industry:

    Cardiovascular drug:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point221 - 223 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.21 g/LNot Available
LogP1.7Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.21 g/LALOGPS
logP1.83ALOGPS
logP1.7ChemAxon
logS-3.3ALOGPS
pKa (Strongest Acidic)9.04ChemAxon
pKa (Strongest Basic)-3.1ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area118.36 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity93.68 m³·mol⁻¹ChemAxon
Polarizability36.92 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-002f-9256200000-2f09810d08c3b35be5f0View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-00di-0353900000-1c8856fba9af1de07f87View in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-00di-0353900000-1c8856fba9af1de07f87View in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-044i-3891000000-67bb3f0457a6200bf63eView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00di-0001900000-1c849cc4bcd762034d79View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0fkc-2418900000-25933e874d81c814b797View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0076-9266000000-3bb75436e40cf56f78f6View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00di-1004900000-f3cae66d652083651bc3View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00di-5917700000-851542f7279cbf5f3d05View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-002f-9000000000-6995f6142329f7f31e6fView in MoNA
Biological Properties
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
Pathways
NameSMPDB/PathwhizKEGG
Bendroflumethiazide PathwayPw000329Pw000329 greyscalePw000329 simpleNot Available
Displaying 1 entry
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00436 details
UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00436 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00436
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID2225
KEGG Compound IDC07758
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkBendroflumethiazide
METLIN IDNot Available
PubChem Compound2315
PDB IDNot Available
ChEBI ID3013
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Download (PDF)
General ReferencesNot Available

Enzymes

General function:
Involved in thiopurine S-methyltransferase activity
Specific function:
Catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine.
Gene Name:
TPMT
Uniprot ID:
P51580
Molecular weight:
28180.09
References
  1. Lysaa RA, Giverhaug T, Wold HL, Aarbakke J: Inhibition of human thiopurine methyltransferase by furosemide, bendroflumethiazide and trichlormethiazide. Eur J Clin Pharmacol. 1996;49(5):393-6. [PubMed:8866635 ]
General function:
Involved in ion channel activity
Specific function:
Potassium channel activated by both membrane depolarization or increase in cytosolic Ca(2+) that mediates export of K(+). It is also activated by the concentration of cytosolic Mg(2+). Its activation dampens the excitatory events that elevate the cytosolic Ca(2+) concentration and/or depolarize the cell membrane. It therefore contributes to repolarization of the membrane potential. Plays a key role in controlling excitability in a number of systems, such as regulation of the contraction of smooth muscle, the tuning of hair cells in the cochlea, regulation of transmitter release, and innate immunity. In smooth muscles, its activation by high level of Ca(2+), caused by ryanodine receptors in the sarcoplasmic reticulum, regulates the membrane potential. In cochlea cells, its number and kinetic properties partly determine the characteristic frequency of each hair cell and thereby helps to establish a tonotopic map. Kinetics of KCNMA1 channels are determined by alternative splicing, phosphorylation status and its combination with modulating beta subunits. Highly sensitive to both iberiotoxin (IbTx) and charybdotoxin (CTX)
Gene Name:
KCNMA1
Uniprot ID:
Q12791
Molecular weight:
137558.1
References
  1. Tricarico D, Barbieri M, Mele A, Carbonara G, Camerino DC: Carbonic anhydrase inhibitors are specific openers of skeletal muscle BK channel of K+-deficient rats. FASEB J. 2004 Apr;18(6):760-1. Epub 2004 Feb 6. [PubMed:14766795 ]
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. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
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. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
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. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  2. Monroy A, Plata C, Hebert SC, Gamba G: Characterization of the thiazide-sensitive Na(+)-Cl(-) cotransporter: a new model for ions and diuretics interaction. Am J Physiol Renal Physiol. 2000 Jul;279(1):F161-9. [PubMed:10894798 ]
  3. Vallon V, Rieg T, Ahn SY, Wu W, Eraly SA, Nigam SK: Overlapping in vitro and in vivo specificities of the organic anion transporters OAT1 and OAT3 for loop and thiazide diuretics. Am J Physiol Renal Physiol. 2008 Apr;294(4):F867-73. doi: 10.1152/ajprenal.00528.2007. Epub 2008 Jan 23. [PubMed:18216144 ]
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. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]