Diltiazem (CHEM002177)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesTargets (6)XML
Record Information
Version1.0
Creation Date2009-07-21 20:26:39 UTC
Update Date2016-11-09 01:08:42 UTC
Accession NumberCHEM002177
Identification
Common NameDiltiazem
ClassSmall Molecule
DescriptionDiltiazem is only found in individuals that have used or taken this drug. It is a benzothiazepine derivative with vasodilating action due to its antagonism of the actions of the calcium ion in membrane functions. It is also teratogenic. Possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, diltiazem, like verapamil, inhibits the influx of extracellular calcium across both the myocardial and vascular smooth muscle cell membranes. The resultant inhibition of the contractile processes of the myocardial smooth muscle cells leads to dilation of the coronary and systemic arteries and improved oxygen delivery to the myocardial tissue.
Contaminant Sources
  • HMDB Contaminants - Urine
  • STOFF IDENT Compounds
  • T3DB toxins
  • ToxCast & Tox21 Chemicals
Contaminant Type
  • Amide
  • Amine
  • Antihypertensive Agent
  • Calcium Channel Blocker
  • Cardiovascular Agent
  • Drug
  • Ester
  • Ether
  • Metabolite
  • Organic Compound
  • Synthetic Compound
  • Vasodilator Agent
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
ValueSource
(+)-cis-5-[2-(Dimethylamino)ethyl]-2,3-dihydro-3-hydroxy-2-(p-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one acetate esterChEBI
(2S,3S)-5-(2-(Dimethylamino)ethyl)-2-(4-methoxyphenyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]thiazepin-3-yl acetateChEBI
(2S-cis)-3-(Acetyloxy)-5-[2-(dimethylamino)ethyl]-2,3-dihydro-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-oneChEBI
Acetic acid (2S,3S)-5-(2-dimethylamino-ethyl)-2-(4-methoxy-phenyl)-4-oxo-2,3,4,5-tetrahydro-benzo[b][1,4]thiazepin-3-yl esterChEBI
D-cis-DiltiazemChEBI
DiltiazemumChEBI
SurazemKegg
(+)-cis-5-[2-(Dimethylamino)ethyl]-2,3-dihydro-3-hydroxy-2-(p-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one acetic acid esterGenerator
(2S,3S)-5-(2-(Dimethylamino)ethyl)-2-(4-methoxyphenyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]thiazepin-3-yl acetic acidGenerator
Acetate (2S,3S)-5-(2-dimethylamino-ethyl)-2-(4-methoxy-phenyl)-4-oxo-2,3,4,5-tetrahydro-benzo[b][1,4]thiazepin-3-yl esterGenerator
CardilHMDB
AldizemHMDB
DilrenHMDB
Watson pharmaceuticals brand OF diltazemHMDB
CRD 401HMDB
CRD-401HMDB
CardizemHMDB
DilacorHMDB
Dilacor XRHMDB
Diltiazem hydrochlorideHMDB
DilzemHMDB
TiazacHMDB
Biovail brand OF diltiazem hydrochlorideHMDB
Diltiazem malateHMDB
Chemical FormulaC22H26N2O4S
Average Molecular Mass414.518 g/mol
Monoisotopic Mass414.161 g/mol
CAS Registry Number42399-41-7
IUPAC Name(2S,3S)-5-[2-(dimethylamino)ethyl]-2-(4-methoxyphenyl)-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepin-3-yl acetate
Traditional Namediltiazem
SMILESCOC1=CC=C(C=C1)[C@@H]1SC2=CC=CC=C2N(CCN(C)C)C(=O)[C@@H]1OC(C)=O
InChI IdentifierInChI=1S/C22H26N2O4S/c1-15(25)28-20-21(16-9-11-17(27-4)12-10-16)29-19-8-6-5-7-18(19)24(22(20)26)14-13-23(2)3/h5-12,20-21H,13-14H2,1-4H3/t20-,21+/m1/s1
InChI KeyHSUGRBWQSSZJOP-RTWAWAEBSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as benzothiazepines. These are organic compounds containing a benzene fused to a thiazepine ring (a seven-membered ring with a nitrogen atom and a sulfur atom replacing two carbon atoms).
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzothiazepines
Sub ClassNot Available
Direct ParentBenzothiazepines
Alternative Parents
Substituents
  • Benzothiazepine
  • Phenoxy compound
  • Aryl thioether
  • Anisole
  • Phenol ether
  • Methoxybenzene
  • Alkyl aryl ether
  • Alkylarylthioether
  • Monocyclic benzene moiety
  • Benzenoid
  • Tertiary carboxylic acid amide
  • Amino acid or derivatives
  • Carboxamide group
  • Carboxylic acid ester
  • Lactam
  • Tertiary amine
  • Tertiary aliphatic amine
  • Monocarboxylic acid or derivatives
  • Ether
  • Carboxylic acid derivative
  • Azacycle
  • Thioether
  • Organonitrogen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Amine
  • Carbonyl group
  • Organic oxide
  • Organooxygen compound
  • Hydrocarbon derivative
  • Organopnictogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
  • 5-[2-(dimethylamino)ethyl]-2-(4-methoxyphenyl)-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepin-3-yl acetate (CHEBI:101278 )
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point187-188°C
Boiling PointNot Available
Solubility465 mg/L (at 25°C)
Predicted Properties
PropertyValueSource
Water Solubility0.017 g/LALOGPS
logP3.09ALOGPS
logP2.73ChemAxon
logS-4.4ALOGPS
pKa (Strongest Acidic)12.86ChemAxon
pKa (Strongest Basic)8.18ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area59.08 ŲChemAxon
Rotatable Bond Count7ChemAxon
Refractivity114.37 m³·mol⁻¹ChemAxon
Polarizability43.65 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0abc-9646000000-04d2eb286617fa811190Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableSpectrum
LC-MS/MSLC-MS/MS Spectrum - 40V, Positivesplash10-0fb9-0900000000-96509d36ba030e8f98c8Spectrum
LC-MS/MSLC-MS/MS Spectrum - 10V, Positivesplash10-014i-0201900000-26955403b59e6618fe76Spectrum
LC-MS/MSLC-MS/MS Spectrum - 20V, Positivesplash10-004i-0901100000-71e8128140c5e1ca0c52Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00xr-3109700000-d386c5de1a87c11cbc6fSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00di-7973000000-0bc5fc09ba611f5ad1feSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-05fr-8911000000-3f9afe9e89e028c0d258Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-9003300000-aa0d02f7d6ac5f92863eSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4i-9138100000-f2b6df8ef6a8cb7aed70Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0pb9-7951000000-c5814417a1eb6c5de03bSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014i-0001900000-8a381f5579f5f7ad42f4Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00di-6918100000-310ffaa05668b4014162Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0229-6958000000-c55c00ddc94a8d826551Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03di-1023900000-78474bb391c4e477c10bSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4i-9188100000-db8c547169ab233cd8d1Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0nov-3149000000-652c4505661022e2d0b6Spectrum
MSMass Spectrum (Electron Ionization)splash10-0ab9-9200000000-b1095b8fe5973d23fdd6Spectrum
Toxicity Profile
Route of ExposureIntravenous, Oral. Diltiazem is well absorbed from the gastrointestinal tract but undergoes substantial hepatic first-pass effect.
Mechanism of ToxicityPossibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, diltiazem, like verapamil, inhibits the influx of extracellular calcium across both the myocardial and vascular smooth muscle cell membranes. The resultant inhibition of the contractile processes of the myocardial smooth muscle cells leads to dilation of the coronary and systemic arteries and improved oxygen delivery to the myocardial tissue.
MetabolismDiltiazem is metabolized by and acts as an inhibitor of the CYP3A4 enzyme. Half Life: 3.0 - 4.5 hours
Toxicity ValuesLD50=740mg/kg (orally in mice)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the treatment of hypertension.
Minimum Risk LevelNot Available
Health EffectsBecause of its negative inotropic effect, diltiazem causes a modest decrease in heart muscle contractility and reduces myocardium oxygen consumption. Its negative chronotropic effect results in a modest lowering of heart rate, due to slowing of the sinoatrial node. It results in reduced myocardium oxygen consumption. Because of its negative dromotropic effect, conduction through the AV (atrioventricular) node is slowed, which increases the time needed for each beat. This results in reduced myocardium oxygen consumption. A reflex sympathetic response, caused by the peripheral dilation of vessels and the resulting drop in blood pressure, works to counteract the negative inotropic, chronotropic and dromotropic effects of diltiazem. Undesirable effects include hypotension, bradycardia, dizziness, and flushing. (Wikipedia)
SymptomsLD50=740mg/kg (orally in mice)
TreatmentIn the event of overdose or exaggerated response, appropriate supportive measures should be employed in addition to gastrointestinal decontamination. If bradycardia and/or high-degree AV block occurs, administer atropine (0.60 to 1.0 mg). If there is no response to vagal blockage, administer isoproterenol cautiously. Fixed high-degree AV block should be treated with cardiac pacing. In cases of cardiac failure, administer inotropic agents (isoproterenol, dopamine, or dobutamine) and diuretics. If hypotension occurs, use vasopressors (e.g. dopamine or levarterenol bitartrate). (2)
Concentrations
Not Available
DrugBank IDDB00343
HMDB IDHMDB0014487
FooDB IDNot Available
Phenol Explorer IDNot Available
KNApSAcK IDNot Available
BiGG IDNot Available
BioCyc IDNot Available
METLIN IDNot Available
PDB IDNot Available
Wikipedia LinkDiltiazem
Chemspider ID35850
ChEBI ID101278
PubChem Compound ID39186
Kegg Compound IDC06958
YMDB IDNot Available
ECMDB IDNot Available
References
Synthesis Reference

Kugita, H., Inoue, H., Ikezaki, M. and Takeo, S.; U.S. Patent 3,562,257; assigned to Tanabe Seiyaku Co.,Ltd., Japan.

MSDSLink
General References
1. https://www.ncbi.nlm.nih.gov/pubmed/?term=11937779
2. https://www.ncbi.nlm.nih.gov/pubmed/?term=16651034
3. https://www.ncbi.nlm.nih.gov/pubmed/?term=19167257
4. https://www.ncbi.nlm.nih.gov/pubmed/?term=23687551
5. https://www.ncbi.nlm.nih.gov/pubmed/?term=24261918
6. https://www.ncbi.nlm.nih.gov/pubmed/?term=25122162
7. https://www.ncbi.nlm.nih.gov/pubmed/?term=8369596