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Record Information
Version5.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:49 UTC
Update Date2021-09-14 14:57:58 UTC
HMDB IDHMDB0014388
Secondary Accession Numbers
  • HMDB14388
Metabolite Identification
Common NameRanolazine
DescriptionRanolazine is only found in individuals that have used or taken this drug. It is an antianginal medication. On January 31, 2006, ranolazine was approved for use in the United States by the FDA for the treatment of chronic angina. [Wikipedia ]The mechanism of action of ranolazine is unknown. It does not increase the rate-pressure product, a measure of myocardial work, at maximal exercise. In vitro studies suggest that ranolazine is a P-gp inhibitor. Ranolazine is believed to have its effects via altering the trans-cellular late sodium current. It is by altering the intracellular sodium level that ranolazine affects the sodium-dependent calcium channels during myocardial ischemia. Thus, ranolazine indirectly prevents the calcium overload that causes cardiac ischemia.
Structure
Data?1582753173
Synonyms
ValueSource
RanexaKegg
(-)-RanolazineHMDB
Ranolazine 2HCLHMDB
HCL, RanolazineMeSH, HMDB
Hydrochloride, ranolazineMeSH, HMDB
Ranolazine hydrochlorideMeSH, HMDB
RenolazineMeSH, HMDB
Dihydrochloride, ranolazineMeSH, HMDB
Ranolazine dihydrochlorideMeSH, HMDB
Ranolazine HCLMeSH, HMDB
N-(2,6-Dimethylphenyl)-4-(2-hydroxy-3-(2-methoxyphenoxy)propyl)-1-piperazineacetamideMeSH, HMDB
RanolazineMeSH
Chemical FormulaC24H33N3O4
Average Molecular Weight427.5365
Monoisotopic Molecular Weight427.247106559
IUPAC NameN-(2,6-dimethylphenyl)-2-{4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]piperazin-1-yl}acetamide
Traditional Nameranolazine
CAS Registry Number142387-99-3
SMILES
COC1=CC=CC=C1OCC(O)CN1CCN(CC(=O)NC2=C(C)C=CC=C2C)CC1
InChI Identifier
InChI=1S/C24H33N3O4/c1-18-7-6-8-19(2)24(18)25-23(29)16-27-13-11-26(12-14-27)15-20(28)17-31-22-10-5-4-9-21(22)30-3/h4-10,20,28H,11-17H2,1-3H3,(H,25,29)
InChI KeyXKLMZUWKNUAPSZ-UHFFFAOYSA-N
Chemical Taxonomy
Description Belongs to the class of organic compounds known as anisoles. These are organic compounds containing a methoxybenzene or a derivative thereof.
KingdomOrganic compounds
Super ClassBenzenoids
ClassPhenol ethers
Sub ClassAnisoles
Direct ParentAnisoles
Alternative Parents
Substituents
  • Phenoxy compound
  • Anisole
  • M-xylene
  • Xylene
  • Methoxybenzene
  • Alkyl aryl ether
  • N-alkylpiperazine
  • Monocyclic benzene moiety
  • 1,4-diazinane
  • Piperazine
  • 1,2-aminoalcohol
  • Secondary alcohol
  • Tertiary amine
  • Tertiary aliphatic amine
  • Carboximidic acid
  • Carboximidic acid derivative
  • Azacycle
  • Ether
  • Organoheterocyclic compound
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Alcohol
  • Organic nitrogen compound
  • Organic oxygen compound
  • Amine
  • Organonitrogen compound
  • Organooxygen compound
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Ontology
Disposition

Biological location

Source

Route of exposure

Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.11 g/LNot Available
LogP1.6Not Available
Experimental Chromatographic Properties

Experimental Collision Cross Sections

Adduct TypeData SourceCCS Value (Å2)Reference
[M+H]+Not Available205.153http://allccs.zhulab.cn/database/detail?ID=AllCCS00000762
Predicted Molecular Properties
PropertyValueSource
Water Solubility0.11 g/LALOGPS
logP10(2.08) g/LALOGPS
logP10(2.83) g/LChemAxon
logS10(-3.6) g/LALOGPS
pKa (Strongest Acidic)13.6ChemAxon
pKa (Strongest Basic)7.17ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area74.27 ŲChemAxon
Rotatable Bond Count9ChemAxon
Refractivity123.46 m³·mol⁻¹ChemAxon
Polarizability47.22 ųChemAxon
Number of Rings3ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted Chromatographic Properties

Predicted Collision Cross Sections

PredictorAdduct TypeCCS Value (Å2)Reference
DarkChem[M+H]+202.02431661259
DarkChem[M-H]-200.90231661259
DeepCCS[M+H]+196.72930932474

Predicted Kovats Retention Indices

Underivatized

MetaboliteSMILESKovats RI ValueColumn TypeReference
RanolazineCOC1=CC=CC=C1OCC(O)CN1CCN(CC(=O)NC2=C(C)C=CC=C2C)CC13927.1Standard polar33892256
RanolazineCOC1=CC=CC=C1OCC(O)CN1CCN(CC(=O)NC2=C(C)C=CC=C2C)CC13445.6Standard non polar33892256
RanolazineCOC1=CC=CC=C1OCC(O)CN1CCN(CC(=O)NC2=C(C)C=CC=C2C)CC13551.5Semi standard non polar33892256

Derivatized

Derivative Name / StructureSMILESKovats RI ValueColumn TypeReference
Ranolazine,1TMS,isomer #1COC1=CC=CC=C1OCC(CN1CCN(CC(=O)NC2=C(C)C=CC=C2C)CC1)O[Si](C)(C)C3469.8Semi standard non polar33892256
Ranolazine,1TMS,isomer #2COC1=CC=CC=C1OCC(O)CN1CCN(CC(=O)N(C2=C(C)C=CC=C2C)[Si](C)(C)C)CC13294.0Semi standard non polar33892256
Ranolazine,2TMS,isomer #1COC1=CC=CC=C1OCC(CN1CCN(CC(=O)N(C2=C(C)C=CC=C2C)[Si](C)(C)C)CC1)O[Si](C)(C)C3289.2Semi standard non polar33892256
Ranolazine,2TMS,isomer #1COC1=CC=CC=C1OCC(CN1CCN(CC(=O)N(C2=C(C)C=CC=C2C)[Si](C)(C)C)CC1)O[Si](C)(C)C3148.9Standard non polar33892256
Ranolazine,2TMS,isomer #1COC1=CC=CC=C1OCC(CN1CCN(CC(=O)N(C2=C(C)C=CC=C2C)[Si](C)(C)C)CC1)O[Si](C)(C)C4361.4Standard polar33892256
Ranolazine,1TBDMS,isomer #1COC1=CC=CC=C1OCC(CN1CCN(CC(=O)NC2=C(C)C=CC=C2C)CC1)O[Si](C)(C)C(C)(C)C3691.9Semi standard non polar33892256
Ranolazine,1TBDMS,isomer #2COC1=CC=CC=C1OCC(O)CN1CCN(CC(=O)N(C2=C(C)C=CC=C2C)[Si](C)(C)C(C)(C)C)CC13500.2Semi standard non polar33892256
Ranolazine,2TBDMS,isomer #1COC1=CC=CC=C1OCC(CN1CCN(CC(=O)N(C2=C(C)C=CC=C2C)[Si](C)(C)C(C)(C)C)CC1)O[Si](C)(C)C(C)(C)C3670.5Semi standard non polar33892256
Ranolazine,2TBDMS,isomer #1COC1=CC=CC=C1OCC(CN1CCN(CC(=O)N(C2=C(C)C=CC=C2C)[Si](C)(C)C(C)(C)C)CC1)O[Si](C)(C)C(C)(C)C3520.6Standard non polar33892256
Ranolazine,2TBDMS,isomer #1COC1=CC=CC=C1OCC(CN1CCN(CC(=O)N(C2=C(C)C=CC=C2C)[Si](C)(C)C(C)(C)C)CC1)O[Si](C)(C)C(C)(C)C4426.0Standard polar33892256
Spectra

GC-MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted GC-MSPredicted GC-MS Spectrum - Ranolazine GC-MS (Non-derivatized) - 70eV, Positivesplash10-00di-0960000000-fec44fb0c944059ff9102017-09-01Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Ranolazine GC-MS (1 TMS) - 70eV, Positivesplash10-00di-3955300000-205c596ad90919eac1442017-10-06Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Ranolazine GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Ranolazine GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Ranolazine GC-MS (TMS_1_2) - 70eV, PositiveNot Available2021-11-03Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Ranolazine GC-MS (TBDMS_1_1) - 70eV, PositiveNot Available2021-11-03Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Ranolazine GC-MS (TBDMS_1_2) - 70eV, PositiveNot Available2021-11-03Wishart LabView Spectrum

MS/MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Experimental LC-MS/MSLC-MS/MS Spectrum - Ranolazine LC-ESI-qTof , Positive-QTOFsplash10-0udi-0010900000-41c6c10d624710416f8e2017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Ranolazine , positive-QTOFsplash10-0udi-0010900000-41c6c10d624710416f8e2017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Ranolazine , positive-QTOFsplash10-004i-1321900000-58e490b47155b2267ecc2017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Ranolazine , positive-QTOFsplash10-004i-1320900000-9a6cdfcd606e98d384522017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Ranolazine , positive-QTOFsplash10-004i-0320900000-ab04122e7d0d6e7c36902017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Ranolazine , positive-QTOFsplash10-004i-5951300000-885e790d3cd4d8746c022017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Ranolazine 35V, Negative-QTOFsplash10-001i-0190000000-6319b1c775f27bd8c8ce2021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Ranolazine 35V, Positive-QTOFsplash10-004i-1240900000-d3069ce6b5d688a4783b2021-09-20HMDB team, MONAView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Ranolazine 10V, Positive-QTOFsplash10-004i-0590200000-2f0530ce2db07c01dbb42016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Ranolazine 20V, Positive-QTOFsplash10-0200-1950000000-1147b10f00f99b50c8282016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Ranolazine 40V, Positive-QTOFsplash10-03di-1900000000-74fa7798b15582c216e52016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Ranolazine 10V, Negative-QTOFsplash10-00b9-0710900000-09291e56b9aef129f8712016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Ranolazine 20V, Negative-QTOFsplash10-05fr-1900000000-9ca0fb6599e918e85e842016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Ranolazine 40V, Negative-QTOFsplash10-0ab9-3900000000-b5af33130090f877b66a2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Ranolazine 10V, Negative-QTOFsplash10-00b9-0884900000-f03ddc85c7181df224752021-09-24Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Ranolazine 20V, Negative-QTOFsplash10-001r-0952100000-7af7dd6f35711dc596952021-09-24Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Ranolazine 40V, Negative-QTOFsplash10-059g-1941200000-b2780a3ccbe1bf73d1a12021-09-24Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Ranolazine 10V, Positive-QTOFsplash10-004i-0005900000-1f0abdb439637a86f8262021-09-24Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Ranolazine 20V, Positive-QTOFsplash10-0fk9-0539100000-5f686a8e215943300bbf2021-09-24Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Ranolazine 40V, Positive-QTOFsplash10-06xy-2920100000-25b7bdd69da447f082932021-09-24Wishart LabView Spectrum
Biological Properties
Cellular Locations
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00243 details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00243 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00243
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID51354
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkRanolazine
METLIN IDNot Available
PubChem CompoundNot Available
PDB IDNot Available
ChEBI ID87690
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB IDNot Available
Good Scents IDNot Available
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Hale SL, Kloner RA: Ranolazine, an inhibitor of the late sodium channel current, reduces postischemic myocardial dysfunction in the rabbit. J Cardiovasc Pharmacol Ther. 2006 Dec;11(4):249-55. [PubMed:17220471 ]
  2. Chaitman BR, Pepine CJ, Parker JO, Skopal J, Chumakova G, Kuch J, Wang W, Skettino SL, Wolff AA: Effects of ranolazine with atenolol, amlodipine, or diltiazem on exercise tolerance and angina frequency in patients with severe chronic angina: a randomized controlled trial. JAMA. 2004 Jan 21;291(3):309-16. [PubMed:14734593 ]
  3. Stone PH, Gratsiansky NA, Blokhin A, Huang IZ, Meng L: Antianginal efficacy of ranolazine when added to treatment with amlodipine: the ERICA (Efficacy of Ranolazine in Chronic Angina) trial. J Am Coll Cardiol. 2006 Aug 1;48(3):566-75. Epub 2006 Jun 15. [PubMed:16875985 ]
  4. Fraser H, Belardinelli L, Wang L, Light PE, McVeigh JJ, Clanachan AS: Ranolazine decreases diastolic calcium accumulation caused by ATX-II or ischemia in rat hearts. J Mol Cell Cardiol. 2006 Dec;41(6):1031-8. Epub 2006 Oct 5. [PubMed:17027025 ]
  5. Morrow DA, Scirica BM, Karwatowska-Prokopczuk E, Murphy SA, Budaj A, Varshavsky S, Wolff AA, Skene A, McCabe CH, Braunwald E: Effects of ranolazine on recurrent cardiovascular events in patients with non-ST-elevation acute coronary syndromes: the MERLIN-TIMI 36 randomized trial. JAMA. 2007 Apr 25;297(16):1775-83. [PubMed:17456819 ]

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
General function:
Involved in monooxygenase activity
Specific function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular weight:
55768.94
General function:
Involved in ion channel activity
Specific function:
This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-resistant Na(+) channel isoform. This channel is responsible for the initial upstroke of the action potential in the electrocardiogram
Gene Name:
SCN5A
Uniprot ID:
Q14524
Molecular weight:
226937.5
References
  1. Hale SL, Kloner RA: Ranolazine, an inhibitor of the late sodium channel current, reduces postischemic myocardial dysfunction in the rabbit. J Cardiovasc Pharmacol Ther. 2006 Dec;11(4):249-55. [PubMed:17220471 ]
  2. Rajamani S, Shryock JC, Belardinelli L: Block of tetrodotoxin-sensitive, Na(V)1.7 and tetrodotoxin-resistant, Na(V)1.8, Na+ channels by ranolazine. Channels (Austin). 2008 Nov-Dec;2(6):449-60. Epub 2008 Nov 7. [PubMed:19077543 ]
General function:
Involved in ion channel activity
Specific function:
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-sensitive Na(+) channel isoform. Plays a role in pain mechanisms, especially in the development of inflammatory pain
Gene Name:
SCN9A
Uniprot ID:
Q15858
Molecular weight:
226340.1
References
  1. Rajamani S, Shryock JC, Belardinelli L: Block of tetrodotoxin-sensitive, Na(V)1.7 and tetrodotoxin-resistant, Na(V)1.8, Na+ channels by ranolazine. Channels (Austin). 2008 Nov-Dec;2(6):449-60. Epub 2008 Nov 7. [PubMed:19077543 ]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]