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Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:51 UTC
Update Date2017-12-07 02:48:44 UTC
HMDB IDHMDB0015024
Secondary Accession Numbers
  • HMDB15024
Metabolite Identification
Common NameBumetanide
DescriptionBumetanide is only found in individuals that have used or taken this drug. It is a sulfamyl diuretic.Bumetanide interferes with renal cAMP and/or inhibits the sodium-potassium ATPase pump. Bumetanide appears to block the active reabsorption of chloride and possibly sodium in the ascending loop of Henle, altering electrolyte transfer in the proximal tubule. This results in excretion of sodium, chloride, and water and, hence, diuresis.
Structure
Thumb
Synonyms
ValueSource
3-(Aminosulfonyl)-5-(butylamino)-4-phenoxybenzoic acidChEBI
3-butylamino-4-(Phenoxy)-5-sulfamoylbenzoic acidChEBI
3-butylamino-4-Phenoxy-5-sulfamoyl-benzoic acidChEBI
3-butylamino-4-Phenoxy-5-sulfamoylbenzoic acidChEBI
BumetanidaChEBI
BumetanidumChEBI
3-(Aminosulfonyl)-5-(butylamino)-4-phenoxybenzoateGenerator
3-(Aminosulphonyl)-5-(butylamino)-4-phenoxybenzoateGenerator
3-(Aminosulphonyl)-5-(butylamino)-4-phenoxybenzoic acidGenerator
3-butylamino-4-(Phenoxy)-5-sulfamoylbenzoateGenerator
3-butylamino-4-(Phenoxy)-5-sulphamoylbenzoateGenerator
3-butylamino-4-(Phenoxy)-5-sulphamoylbenzoic acidGenerator
3-butylamino-4-Phenoxy-5-sulfamoyl-benzoateGenerator
3-butylamino-4-Phenoxy-5-sulphamoyl-benzoateGenerator
3-butylamino-4-Phenoxy-5-sulphamoyl-benzoic acidGenerator
3-butylamino-4-Phenoxy-5-sulfamoylbenzoateGenerator
3-butylamino-4-Phenoxy-5-sulphamoylbenzoateGenerator
3-butylamino-4-Phenoxy-5-sulphamoylbenzoic acidGenerator
Atlantis brand OF bumetanideMeSH
BumedylMeSH
Bumetanide astrazeneca brandMeSH
BumethanideMeSH
FordiuranMeSH
Senosiain brand OF bumetanideMeSH
Bumetanide farmacusi brandMeSH
Bumetanide leo brandMeSH
Bumetanide atlantis brandMeSH
Bumetanide senosiain brandMeSH
BumexMeSH
DrenuralMeSH
Farmacusi brand OF bumetanideMeSH
leo Brand OF bumetanideMeSH
Roche brand OF bumetanideMeSH
AstraZeneca brand OF bumetanideMeSH
Bumetanide grossmann brandMeSH
Bumetanide roche brandMeSH
BurinexMeSH
Grossmann brand OF bumetanideMeSH
MiccilMeSH
Chemical FormulaC17H20N2O5S
Average Molecular Weight364.416
Monoisotopic Molecular Weight364.10929245
IUPAC Name3-(butylamino)-4-phenoxy-5-sulfamoylbenzoic acid
Traditional Namebumetanide
CAS Registry Number28395-03-1
SMILES
CCCCNC1=C(OC2=CC=CC=C2)C(=CC(=C1)C(O)=O)S(N)(=O)=O
InChI Identifier
InChI=1S/C17H20N2O5S/c1-2-3-9-19-14-10-12(17(20)21)11-15(25(18,22)23)16(14)24-13-7-5-4-6-8-13/h4-8,10-11,19H,2-3,9H2,1H3,(H,20,21)(H2,18,22,23)
InChI KeyMAEIEVLCKWDQJH-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as diphenylethers. These are aromatic compounds containing two benzene rings linked to each other through an ether group.
KingdomChemical entities
Super ClassOrganic compounds
ClassBenzenoids
Sub ClassBenzene and substituted derivatives
Direct ParentDiphenylethers
Alternative Parents
Substituents
  • Diphenylether
  • Aminobenzenesulfonamide
  • Diaryl ether
  • Aminobenzoic acid
  • Aminobenzoic acid or derivatives
  • Benzenesulfonamide
  • Benzoic acid or derivatives
  • Benzenesulfonyl group
  • Benzoic acid
  • Phenoxy compound
  • Benzoyl
  • Phenol ether
  • Aniline or substituted anilines
  • Phenylalkylamine
  • Secondary aliphatic/aromatic amine
  • Organosulfonic acid amide
  • Organosulfonic acid or derivatives
  • Organic sulfonic acid or derivatives
  • Aminosulfonyl compound
  • Sulfonyl
  • Amino acid
  • Amino acid or derivatives
  • Secondary amine
  • Monocarboxylic acid or derivatives
  • Ether
  • Carboxylic acid
  • Carboxylic acid derivative
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Organic oxide
  • Organopnictogen compound
  • Organooxygen compound
  • Organosulfur compound
  • Organic nitrogen compound
  • Amine
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Ontology
Disposition

Biological Location:

  Subcellular:

  Biofluid and excreta:

Process

Naturally occurring process:

  Biological process:

    Biochemical pathway:

Role

Industrial application:

  Pharmaceutical industry:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point230 - 231 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.026 g/LNot Available
LogP2.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.026 g/LALOGPS
logP3.44ALOGPS
logP2.42ChemAxon
logS-4.2ALOGPS
pKa (Strongest Acidic)4.69ChemAxon
pKa (Strongest Basic)2.7ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area118.72 ŲChemAxon
Rotatable Bond Count8ChemAxon
Refractivity95.78 m³·mol⁻¹ChemAxon
Polarizability37.21 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-MS (Non-derivatized) - 70eV, Positivesplash10-000w-7198000000-9c32fd3e7109756cbcbbView in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-00dj-9034300000-5a798c87f87ef51b1527View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-00lu-1694000000-dbf4d76ea1a12ee57935View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-00lu-0594000000-78579410f8f6799b400bView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-03di-0009000000-2a72173931dce5701622View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-03di-0119000000-4abf1963718d72f73f59View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-001i-9351000000-b43658e112020008b9f9View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-001i-9100000000-4d303174266311856c28View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-001i-9000000000-2d120289f52c86515beaView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-014i-0009000000-97827d479a3470c40d42View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-015c-0396000000-5edaaa0fcc7cd3681c24View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-000x-0980000000-0b360ca9bf4e58649db7View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-053s-0910000000-c5fc710abfdf5947bc62View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-0a4j-0900000000-368c9661bc6dfd8a8d83View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-IT , positivesplash10-000x-0291000000-134f42a8645c2f1b9bc5View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-014i-0009000000-e4d18d4c63310d0528dbView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-000x-0390000000-abfea32acc207ff88b1fView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-053r-0930000000-cc33040126bfe7cb08faView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0a5a-0910000000-42b9627a1135073b6ce1View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0ars-0900000000-d22f5ff182cd71ced792View in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-00lu-0594000000-78579410f8f6799b400bView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014i-1009000000-09e85edf114cc804bbf1View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0aor-5079000000-0fed70d52a46e216c387View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0r00-8490000000-249e2af61c2ace14276bView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03di-4009000000-a4f63b404f4b2683d366View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0404-7479000000-109242300f7a6e750327View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-01t9-9410000000-89f0a65fb708b0eac550View in MoNA
Biological Properties
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
Pathways
NameSMPDB/PathwhizKEGG
Bumetanide PathwayPw000328Pw000328 greyscalePw000328 simpleNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00887 details
UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00887 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00887
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID2377
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkBumetanide
METLIN IDNot Available
PubChem Compound2471
PDB IDNot Available
ChEBI ID3213
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Download (PDF)
General ReferencesNot Available

Enzymes

General function:
Involved in peroxidase activity
Specific function:
Mediates the formation of prostaglandins from arachidonate. May have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity.
Gene Name:
PTGS2
Uniprot ID:
P35354
Molecular weight:
68995.625
References
  1. Cheng HF, Wang JL, Zhang MZ, McKanna JA, Harris RC: Role of p38 in the regulation of renal cortical cyclooxygenase-2 expression by extracellular chloride. J Clin Invest. 2000 Sep;106(5):681-8. [PubMed:10974021 ]
General function:
Involved in ATP binding
Specific function:
Involved in the transport of chloride ions. May regulate bicarbonate secretion and salvage in epithelial cells by regulating the SLC4A7 transporter. Can inhibit the chloride channel activity of ANO1.
Gene Name:
CFTR
Uniprot ID:
P13569
Molecular weight:
168139.895
References
  1. Reddy MM, Quinton PM: Bumetanide blocks CFTR GCl in the native sweat duct. Am J Physiol. 1999 Jan;276(1 Pt 1):C231-7. [PubMed:9886939 ]

Transporters

General function:
Involved in transporter activity
Specific function:
Mediates saturable uptake of estrone sulfate, dehydroepiandrosterone sulfate and related compounds
Gene Name:
SLC22A11
Uniprot ID:
Q9NSA0
Molecular weight:
59970.9
References
  1. Cha SH, Sekine T, Kusuhara H, Yu E, Kim JY, Kim DK, Sugiyama Y, Kanai Y, Endou H: Molecular cloning and characterization of multispecific organic anion transporter 4 expressed in the placenta. J Biol Chem. 2000 Feb 11;275(6):4507-12. [PubMed:10660625 ]
General function:
Involved in transport
Specific function:
Mediates electroneutral potassium-chloride cotransport in mature neurons. Transport occurs under isotonic conditions, but is activated 20-fold by cell swelling. Important for Cl(-) homeostasis in neurons
Gene Name:
SLC12A5
Uniprot ID:
Q9H2X9
Molecular weight:
126182.5
References
  1. Reid KH, Guo SZ, Iyer VG: Agents which block potassium-chloride cotransport prevent sound-triggered seizures in post-ischemic audiogenic seizure-prone rats. Brain Res. 2000 May 2;864(1):134-7. [PubMed:10793196 ]
General function:
Involved in bile acid:sodium symporter activity
Specific function:
The hepatic sodium/bile acid uptake system exhibits broad substrate specificity and transports various non-bile acid organic compounds as well. It is strictly dependent on the extracellular presence of sodium.
Gene Name:
SLC10A1
Uniprot ID:
Q14973
Molecular weight:
38118.64
References
  1. Hagenbuch B, Stieger B, Foguet M, Lubbert H, Meier PJ: Functional expression cloning and characterization of the hepatocyte Na+/bile acid cotransport system. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10629-33. [PubMed:1961729 ]
  2. Platte HD, Honscha W, Schuh K, Petzinger E: Functional characterization of the hepatic sodium-dependent taurocholate transporter stably transfected into an immortalized liver-derived cell line and V79 fibroblasts. Eur J Cell Biol. 1996 May;70(1):54-60. [PubMed:8738419 ]
General function:
Involved in transporter activity
Specific function:
Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids
Gene Name:
SLCO1A2
Uniprot ID:
P46721
Molecular weight:
74144.1
References
  1. Horz JA, Honscha W, Petzinger E: Bumetanide is not transported by the Ntcp or by the oatp: evidence for a third organic anion transporter in rat liver cells. Biochim Biophys Acta. 1996 Apr 19;1300(2):114-8. [PubMed:8652636 ]
General function:
Involved in transport
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
Molecular weight:
131445.8
References
  1. Panet R, Marcus M, Atlan H: Overexpression of the Na(+)/K(+)/Cl(-) cotransporter gene induces cell proliferation and phenotypic transformation in mouse fibroblasts. J Cell Physiol. 2000 Jan;182(1):109-18. [PubMed:10567922 ]
  2. Evans RL, Park K, Turner RJ, Watson GE, Nguyen HV, Dennett MR, Hand AR, Flagella M, Shull GE, Melvin JE: Severe impairment of salivation in Na+/K+/2Cl- cotransporter (NKCC1)-deficient mice. J Biol Chem. 2000 Sep 1;275(35):26720-6. [PubMed:10831596 ]
  3. Wall SM, Fischer MP, Mehta P, Hassell KA, Park SJ: Contribution of the Na+-K+-2Cl- cotransporter NKCC1 to Cl- secretion in rat OMCD. Am J Physiol Renal Physiol. 2001 May;280(5):F913-21. [PubMed:11292635 ]
  4. Akar F, Jiang G, Paul RJ, O'Neill WC: Contractile regulation of the Na(+)-K(+)-2Cl(-) cotransporter in vascular smooth muscle. Am J Physiol Cell Physiol. 2001 Aug;281(2):C579-84. [PubMed:11443057 ]
  5. Jiang G, Klein JD, O'Neill WC: Growth factors stimulate the Na-K-2Cl cotransporter NKCC1 through a novel Cl(-)-dependent mechanism. Am J Physiol Cell Physiol. 2001 Dec;281(6):C1948-53. [PubMed:11698253 ]
General function:
Involved in transport
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
Molecular weight:
121449.1
References
  1. Thakker RV: Chloride channels in renal disease. Adv Nephrol Necker Hosp. 1999;29:289-98. [PubMed:10561751 ]
  2. Karolyi L, Koch MC, Grzeschik KH, Seyberth HW: The molecular genetic approach to "Bartter's syndrome". J Mol Med (Berl). 1998 Apr;76(5):317-25. [PubMed:9587066 ]
  3. Thakker RV: The role of renal chloride channel mutations in kidney stone disease and nephrocalcinosis. Curr Opin Nephrol Hypertens. 1998 Jul;7(4):385-8. [PubMed:9690036 ]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  5. Long P, Mercer A, Begum R, Stephens GJ, Sihra TS, Jovanovic JN: Nerve Terminal GABAA Receptors Activate Ca2+/Calmodulin-dependent Signaling to Inhibit Voltage-gated Ca2+ Influx and Glutamate Release. J Biol Chem. 2009 Mar 27;284(13):8726-37. doi: 10.1074/jbc.M805322200. Epub 2009 Jan 13. [PubMed:19141616 ]
General function:
Involved in transport
Specific function:
Mediates electroneutral potassium-chloride cotransport when activated by cell swelling. May contribute to cell volume homeostasis in single cells. May be involved in the regulation of basolateral Cl(-) exit in NaCl absorbing epithelia. Isoform 4 has no transport activity
Gene Name:
SLC12A4
Uniprot ID:
Q9UP95
Molecular weight:
120648.7
References
  1. Jean-Xavier C, Pflieger JF, Liabeuf S, Vinay L: Inhibitory postsynaptic potentials in lumbar motoneurons remain depolarizing after neonatal spinal cord transection in the rat. J Neurophysiol. 2006 Nov;96(5):2274-81. Epub 2006 Jun 28. [PubMed:16807348 ]
  2. Reid KH, Guo SZ, Iyer VG: Agents which block potassium-chloride cotransport prevent sound-triggered seizures in post-ischemic audiogenic seizure-prone rats. Brain Res. 2000 May 2;864(1):134-7. [PubMed:10793196 ]
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. Race JE, Grassl SM, Williams WJ, Holtzman EJ: Molecular cloning and characterization of two novel human renal organic anion transporters (hOAT1 and hOAT3). Biochem Biophys Res Commun. 1999 Feb 16;255(2):508-14. [PubMed:10049739 ]
  2. 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 ]
General function:
Involved in transmembrane transport
Specific function:
Mediates sodium-independent multispecific organic anion transport. Transport of prostaglandin E2, prostaglandin F2, tetracycline, bumetanide, estrone sulfate, glutarate, dehydroepiandrosterone sulfate, allopurinol, 5-fluorouracil, paclitaxel, L-ascorbic acid, salicylate, ethotrexate, and alpha- ketoglutarate
Gene Name:
SLC22A7
Uniprot ID:
Q9Y694
Molecular weight:
60025.0
References
  1. Sekine T, Cha SH, Tsuda M, Apiwattanakul N, Nakajima N, Kanai Y, Endou H: Identification of multispecific organic anion transporter 2 expressed predominantly in the liver. FEBS Lett. 1998 Jun 12;429(2):179-82. [PubMed:9650585 ]