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Record Information
Version5.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:52 UTC
Update Date2022-03-07 02:52:00 UTC
HMDB IDHMDB0015512
Secondary Accession Numbers
  • HMDB15512
Metabolite Identification
Common NameClotiazepam
DescriptionClotiazepam, also known as rize, belongs to the class of organic compounds known as thienodiazepines. These are heteropolycyclic containing a thiophene ring fused to a diazepine ring. Thiophene is 5-membered ring consisting of four carbon and one sulfur atoms. Diazepine is a 7-membered ring consisting of five carbon and two nitrogen atoms. Clotiazepam is metabolised to hydroxy-clotiazepam and desmethyl-clotiazepam. Clotiazepam is a drug which is used for the treatment of anxiety disorders. Clotiazepam binds to the benzodiazepine site of the GABAA receptor where it acts as a full agonist; this action results in an enhanced GABA inhibitory effect at the GABAA receptor which results in the pharmacological effects of clotiazepam. Clotiazepam is a moderately basic compound (based on its pKa). Clotiazepam is a potentially toxic compound. It is metabolised via oxidation. The use of drops is suggested for a more marked initial effect and the sublingual route for easier administration, especially in the elderly. There has been a report of hepatitis caused by clotiazepam.
Structure
Data?1582753305
Synonyms
ValueSource
RizeKegg
Chemical FormulaC16H15ClN2OS
Average Molecular Weight318.821
Monoisotopic Molecular Weight318.059361509
IUPAC Name5-(2-chlorophenyl)-7-ethyl-1-methyl-1H,2H,3H-thieno[2,3-e][1,4]diazepin-2-one
Traditional NameRize
CAS Registry Number33671-46-4
SMILES
CCC1=CC2=C(S1)N(C)C(=O)CN=C2C1=CC=CC=C1Cl
InChI Identifier
InChI=1S/C16H15ClN2OS/c1-3-10-8-12-15(11-6-4-5-7-13(11)17)18-9-14(20)19(2)16(12)21-10/h4-8H,3,9H2,1-2H3
InChI KeyCHBRHODLKOZEPZ-UHFFFAOYSA-N
Chemical Taxonomy
Description Belongs to the class of organic compounds known as thienodiazepines. These are heteropolycyclic containing a thiophene ring fused to a diazepine ring. Thiophene is 5-membered ring consisting of four carbon and one sulfur atoms. Diazepine is a 7-membered ring consisting of five carbon and two nitrogen atoms.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassThienodiazepines
Sub ClassNot Available
Direct ParentThienodiazepines
Alternative Parents
Substituents
  • Alpha-amino acid or derivatives
  • Thieno-para-diazepine
  • 2,3,5-trisubstituted thiophene
  • Para-diazepine
  • Chlorobenzene
  • Halobenzene
  • Aryl chloride
  • Aryl halide
  • Monocyclic benzene moiety
  • Benzenoid
  • Heteroaromatic compound
  • Thiophene
  • Tertiary carboxylic acid amide
  • Carboxamide group
  • Ketimine
  • Lactam
  • Azacycle
  • Carboxylic acid derivative
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Imine
  • Organopnictogen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Carbonyl group
  • Hydrocarbon derivative
  • Organic oxide
  • Organooxygen compound
  • Organonitrogen compound
  • Organohalogen compound
  • Organochloride
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Ontology
Physiological effectNot Available
Disposition
ProcessNot Available
RoleNot Available
Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting Point118 - 120 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.0054 g/LNot Available
LogP3.18MARUYAMA,T ET AL. (1992)
Experimental Chromatographic PropertiesNot Available
Predicted Molecular Properties
PropertyValueSource
Water Solubility0.0054 g/LALOGPS
logP3.58ALOGPS
logP4.11ChemAxon
logS-4.8ALOGPS
pKa (Strongest Basic)2.39ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area32.67 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity85.66 m³·mol⁻¹ChemAxon
Polarizability33.01 ųChemAxon
Number of Rings3ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted Chromatographic Properties

Predicted Collision Cross Sections

PredictorAdduct TypeCCS Value (Å2)Reference
DeepCCS[M+H]+163.5730932474
DeepCCS[M-H]-161.21230932474
DeepCCS[M-2H]-194.4530932474
DeepCCS[M+Na]+169.67730932474
AllCCS[M+H]+170.332859911
AllCCS[M+H-H2O]+166.832859911
AllCCS[M+NH4]+173.532859911
AllCCS[M+Na]+174.432859911
AllCCS[M-H]-175.932859911
AllCCS[M+Na-2H]-175.732859911
AllCCS[M+HCOO]-175.632859911

Predicted Kovats Retention Indices

Underivatized

MetaboliteSMILESKovats RI ValueColumn TypeReference
ClotiazepamCCC1=CC2=C(S1)N(C)C(=O)CN=C2C1=CC=CC=C1Cl3783.5Standard polar33892256
ClotiazepamCCC1=CC2=C(S1)N(C)C(=O)CN=C2C1=CC=CC=C1Cl2516.4Standard non polar33892256
ClotiazepamCCC1=CC2=C(S1)N(C)C(=O)CN=C2C1=CC=CC=C1Cl2470.9Semi standard non polar33892256
Spectra

GC-MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted GC-MSPredicted GC-MS Spectrum - Clotiazepam GC-MS (Non-derivatized) - 70eV, Positivesplash10-0iki-0492000000-857499d04130284e4e312017-09-01Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Clotiazepam GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Clotiazepam GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum
MSMass Spectrum (Electron Ionization)splash10-014u-3494000000-432038f1e527960b02fc2014-09-20Not AvailableView Spectrum

MS/MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Clotiazepam 10V, Positive-QTOFsplash10-014i-0049000000-45282a7515b9494775c72016-06-20Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Clotiazepam 20V, Positive-QTOFsplash10-014i-1159000000-1ff3be2c8d5ba546d7e82016-06-20Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Clotiazepam 40V, Positive-QTOFsplash10-0a4i-9300000000-d8aa0cda66e62a6b96f72016-06-20Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Clotiazepam 10V, Negative-QTOFsplash10-014i-0029000000-e488e2ee1deb04a7e3372016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Clotiazepam 20V, Negative-QTOFsplash10-014i-2797000000-62a84846bdd05fc7140f2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Clotiazepam 40V, Negative-QTOFsplash10-0a6r-9660000000-74eeddd7f53b2ae0bde12016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Clotiazepam 10V, Positive-QTOFsplash10-014i-0009000000-8f50d8b62b53d25c58b22021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Clotiazepam 20V, Positive-QTOFsplash10-014i-0029000000-1fe711e000cbbd0f052a2021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Clotiazepam 40V, Positive-QTOFsplash10-003i-0981000000-3c7f1bd750ea8ca9f79b2021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Clotiazepam 10V, Negative-QTOFsplash10-014i-0009000000-e086905fb0819f34744f2021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Clotiazepam 20V, Negative-QTOFsplash10-00lr-9066000000-d3f402d10fb32f4ff8c22021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Clotiazepam 40V, Negative-QTOFsplash10-001i-5190000000-2dc5059b047387d48b892021-10-11Wishart 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 DB01559 details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01559 details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiospecimenValueOriginal ageOriginal sexOriginal conditionComments
Blood0.000 uMAdult (>18 years old)BothNormalPredicted based on drug qualities
Blood0.000 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB01559
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID2709
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkClotiazepam
METLIN IDNot Available
PubChem Compound2811
PDB IDNot Available
ChEBI ID1178501
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. Nakazawa Y, Kotorii M, Oshima M, Horikawa S, Tachibana H: Effects of thienodiazepine derivatives on human sleep as compared to those of benzodiazepine derivatives. Psychopharmacologia. 1975 Oct 31;44(2):165-71. [PubMed:709 ]

Only showing the first 10 proteins. There are 20 proteins in total.

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. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
General function:
Involved in monooxygenase activity
Specific function:
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular weight:
55944.565
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
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 oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP2C18
Uniprot ID:
P33260
Molecular weight:
55710.075
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
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 oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,4-cineole 2-exo-monooxygenase.
Gene Name:
CYP2B6
Uniprot ID:
P20813
Molecular weight:
56277.81
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
General function:
Involved in ion transport
Specific function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel
Gene Name:
GABRG2
Uniprot ID:
P18507
Molecular weight:
54161.8
References
  1. Baburin I, Khom S, Timin E, Hohaus A, Sieghart W, Hering S: Estimating the efficiency of benzodiazepines on GABA(A) receptors comprising gamma1 or gamma2 subunits. Br J Pharmacol. 2008 Oct;155(3):424-33. doi: 10.1038/bjp.2008.271. Epub 2008 Jul 7. [PubMed:18604239 ]
  2. Mandrioli R, Mercolini L, Raggi MA: Benzodiazepine metabolism: an analytical perspective. Curr Drug Metab. 2008 Oct;9(8):827-44. [PubMed:18855614 ]
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235 ]
General function:
Involved in ion transport
Specific function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel
Gene Name:
GABRA1
Uniprot ID:
P14867
Molecular weight:
51801.4
References
  1. Baburin I, Khom S, Timin E, Hohaus A, Sieghart W, Hering S: Estimating the efficiency of benzodiazepines on GABA(A) receptors comprising gamma1 or gamma2 subunits. Br J Pharmacol. 2008 Oct;155(3):424-33. doi: 10.1038/bjp.2008.271. Epub 2008 Jul 7. [PubMed:18604239 ]
  2. Mandrioli R, Mercolini L, Raggi MA: Benzodiazepine metabolism: an analytical perspective. Curr Drug Metab. 2008 Oct;9(8):827-44. [PubMed:18855614 ]
General function:
Involved in ion transport
Specific function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel
Gene Name:
GABRA2
Uniprot ID:
P47869
Molecular weight:
51325.9
References
  1. Mandrioli R, Mercolini L, Raggi MA: Benzodiazepine metabolism: an analytical perspective. Curr Drug Metab. 2008 Oct;9(8):827-44. [PubMed:18855614 ]
General function:
Involved in ion transport
Specific function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel
Gene Name:
GABRA3
Uniprot ID:
P34903
Molecular weight:
55164.1
References
  1. Mandrioli R, Mercolini L, Raggi MA: Benzodiazepine metabolism: an analytical perspective. Curr Drug Metab. 2008 Oct;9(8):827-44. [PubMed:18855614 ]
General function:
Involved in ion transport
Specific function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel
Gene Name:
GABRA5
Uniprot ID:
P31644
Molecular weight:
52145.6
References
  1. Mandrioli R, Mercolini L, Raggi MA: Benzodiazepine metabolism: an analytical perspective. Curr Drug Metab. 2008 Oct;9(8):827-44. [PubMed:18855614 ]
General function:
Involved in ion transport
Specific function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel
Gene Name:
GABRB1
Uniprot ID:
P18505
Molecular weight:
54234.1
References
  1. Mandrioli R, Mercolini L, Raggi MA: Benzodiazepine metabolism: an analytical perspective. Curr Drug Metab. 2008 Oct;9(8):827-44. [PubMed:18855614 ]

Only showing the first 10 proteins. There are 20 proteins in total.