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Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:50 UTC
Update Date2020-02-26 21:40:39 UTC
HMDB IDHMDB0014946
Secondary Accession Numbers
  • HMDB14946
Metabolite Identification
Common NameIndapamide
DescriptionIndapamide, also known as lozol or natrix, belongs to the class of organic compounds known as benzenesulfonamides. These are organic compounds containing a sulfonamide group that is S-linked to a benzene ring. However, it differs chemically from the thiazides in that it does not possess the thiazide ring system and contains only one sulfonamide group. Indapamide is also thought to stimulate the synthesis of the vasodilatory hypotensive prostaglandin PGE2. Indapamide is a drug which is used for the treatment of hypertension, alone or in combination with other antihypertensive drugs, as well as for the treatment of salt and fluid retention associated with congestive heart failure or edema from pregnancy (appropriate only in the management of edema of pathologic origin during pregnancy when clearly needed). also used for the management of edema as a result of various causes. Indapamide is an extremely weak basic (essentially neutral) compound (based on its pKa). indapamide can be converted into indapamide; which is catalyzed by the enzyme solute carrier family 22 member 6. In humans, indapamide is involved in indapamide action pathway. Indapamide has also been shown to cause uterine myometrial relaxation in experimental animals. It is called a thiazide-like diuretic but structure is different enough (lacking the thiazo-ring) so it is not clear that the mechanism is comparable. Specifically it blocks or antagonizes the action the proteins KCNQ1 and KCNE1. Indapamide blocks the slow component of delayed rectifier potassium current (IKs) without altering the rapid component (IKr) or the inward rectifier current.
Structure
Data?1582753239
Synonyms
ValueSource
IndapamidaChEBI
IndapamidumChEBI
LozolKegg
NatrixKegg
MetindamideHMDB
Chemical FormulaC16H16ClN3O3S
Average Molecular Weight365.835
Monoisotopic Molecular Weight365.06008979
IUPAC Name4-chloro-N-(2-methyl-2,3-dihydro-1H-indol-1-yl)-3-sulfamoylbenzamide
Traditional Nameindapamide
CAS Registry Number26807-65-8
SMILES
CC1CC2=CC=CC=C2N1NC(=O)C1=CC(=C(Cl)C=C1)S(N)(=O)=O
InChI Identifier
InChI=1S/C16H16ClN3O3S/c1-10-8-11-4-2-3-5-14(11)20(10)19-16(21)12-6-7-13(17)15(9-12)24(18,22)23/h2-7,9-10H,8H2,1H3,(H,19,21)(H2,18,22,23)
InChI KeyNDDAHWYSQHTHNT-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as benzenesulfonamides. These are organic compounds containing a sulfonamide group that is S-linked to a benzene ring.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzenesulfonamides
Direct ParentBenzenesulfonamides
Alternative Parents
Substituents
  • Benzenesulfonamide
  • Halobenzoic acid or derivatives
  • 4-halobenzoic acid or derivatives
  • Benzoic acid or derivatives
  • Benzenesulfonyl group
  • Indole or derivatives
  • Benzoyl
  • Chlorobenzene
  • Halobenzene
  • Aryl chloride
  • Aryl halide
  • Organosulfonic acid amide
  • Aminosulfonyl compound
  • Sulfonyl
  • Organosulfonic acid or derivatives
  • Organic sulfonic acid or derivatives
  • Carboxylic acid hydrazide
  • Organoheterocyclic compound
  • Azacycle
  • Carboxylic acid derivative
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Organosulfur compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Organooxygen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
Disposition

Biological location:

Process

Naturally occurring process:

Role

Industrial application:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point161 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.034 g/LNot Available
LogP2.2Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.034 g/LALOGPS
logP2.52ALOGPS
logP2.64ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)8.85ChemAxon
pKa (Strongest Basic)0.097ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area92.5 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity103.31 m³·mol⁻¹ChemAxon
Polarizability36.34 ųChemAxon
Number of Rings3ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-014i-4593000000-5ea2b9ed9ba04df04bf7Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-001i-1900000000-861314def0ccc019ac04Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-03di-0009000000-ed04e0a5871badc8b166Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-03di-1729000000-15aecb441ef4febfe526Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-000i-2910000000-b72aeba8db62ebdf9c17Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-004r-6900000000-f819fedd1ac654d46dd4Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-004i-9300000000-164a2972880c967d2195Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-004i-9100000000-d18afa355f919614b652Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-01t9-9000000000-9d9e98925e9105738992Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-03fr-9000000000-5e7568f4efd1730f47b9Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-03di-9000000000-ecfffadaaa03b447eaf5Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-001i-0904000000-530b78f6cae834e11768Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-001i-0900000000-235673a939e2e7d8c5e3Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0159-0900000000-a843660d42ffb01666feSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-001i-0900000000-cfee205b361c580e3631Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-00lr-0900000000-a6d8ff4d769ea09e8073Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-001i-0901000000-a76c5fd366807c180552Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-001i-0900000000-574a71dcc7f0b3f74693Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-001i-1900000000-ab046a8849c404d9b308Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-00l6-4900000000-93f1cc6465f329fd111eSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014i-0209000000-9154e3b65e4d452dacb3Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00ls-0968000000-bfc678a87120a2f04f23Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-014i-0920000000-26f53b22345a5ccf8302Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03di-1119000000-10d511f58b646ce4b134Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-01t9-9558000000-8fe9e9ce749aec787743Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-004i-9210000000-6029683889b96e37eacbSpectrum
Biological Properties
Cellular Locations
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00808 details
UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00808 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00808
Phenol Explorer Compound IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID3574
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkIndapamide
METLIN IDNot Available
PubChem Compound3702
PDB IDNot Available
ChEBI ID5893
Food Biomarker OntologyNot Available
VMH IDNot Available
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Dong DL, Wang QH, Yue P, Jiao JD, Gu RM, Yang BF: Indapamide induces apoptosis of GH3 pituitary cells independently of its inhibition of voltage-dependent K+ currents. Eur J Pharmacol. 2006 Apr 24;536(1-2):78-84. Epub 2006 Mar 2. [PubMed:16556441 ]

Enzymes

General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
References
  1. Sun H, Moore C, Dansette PM, Kumar S, Halpert JR, Yost GS: Dehydrogenation of the indoline-containing drug 4-chloro-N-(2-methyl-1-indolinyl)-3-sulfamoylbenzamide (indapamide) by CYP3A4: correlation with in silico predictions. Drug Metab Dispos. 2009 Mar;37(3):672-84. doi: 10.1124/dmd.108.022707. Epub 2008 Dec 12. [PubMed:19074530 ]
General function:
Involved in ion channel activity
Specific function:
Probably important in cardiac repolarization. Associates with KCNE1 (MinK) to form the I(Ks) cardiac potassium current. Elicits a rapidly activating, potassium-selective outward current. Muscarinic agonist oxotremorine-M strongly suppresses KCNQ1/KCNE1 current in CHO cells in which cloned KCNQ1/KCNE1 channels were coexpressed with M1 muscarinic receptors. May associate also with KCNE3 (MiRP2) to form the potassium channel that is important for cyclic AMP-stimulated intestinal secretion of chloride ions, which is reduced in cystic fibrosis and pathologically stimulated in cholera and other forms of secretory diarrhea
Gene Name:
KCNQ1
Uniprot ID:
P51787
Molecular weight:
74697.9
References
  1. Ohya S, Asakura K, Muraki K, Watanabe M, Imaizumi Y: Molecular and functional characterization of ERG, KCNQ, and KCNE subtypes in rat stomach smooth muscle. Am J Physiol Gastrointest Liver Physiol. 2002 Feb;282(2):G277-87. [PubMed:11804849 ]
  2. Li RA, Miake J, Hoppe UC, Johns DC, Marban E, Nuss HB: Functional consequences of the arrhythmogenic G306R KvLQT1 K+ channel mutant probed by viral gene transfer in cardiomyocytes. J Physiol. 2001 May 15;533(Pt 1):127-33. [PubMed:11351021 ]
  3. 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 voltage-gated potassium channel activity
Specific function:
Ancillary protein that assembles as a beta subunit with a voltage-gated potassium channel complex of pore-forming alpha subunits. Modulates the gating kinetics and enhances stability of the channel complex. Assembled with KCNQ1/KVLQT1 is proposed to form the slowly activating delayed rectifier cardiac potassium (IKs) channel. The outward current reaches its steady state only after 50 seconds. Assembled with KCNH2/HERG may modulate the rapidly activating component of the delayed rectifying potassium current in heart (IKr)
Gene Name:
KCNE1
Uniprot ID:
P15382
Molecular weight:
14674.7
References
  1. Ohya S, Asakura K, Muraki K, Watanabe M, Imaizumi Y: Molecular and functional characterization of ERG, KCNQ, and KCNE subtypes in rat stomach smooth muscle. Am J Physiol Gastrointest Liver Physiol. 2002 Feb;282(2):G277-87. [PubMed:11804849 ]