ContaminantDB: Brotizolam

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Targets (19)XML

Record Information

Version

1.0

Creation Date

2014-08-30 21:06:29 UTC

Update Date

2016-11-09 01:09:09 UTC

Accession Number

CHEM003533

Identification

Common Name

Brotizolam

Class

Small Molecule

Description

Brotizolam is a sedative-hypnotic thienodiazepine drug which is a benzodiazepine analog. It possesses anxiolytic, anticonvulsant, hypnotic, sedative and skeletal muscle relaxant properties, and is considered to be similar in effect to short-acting benzodiazepines such as triazolam. It is used in the short term treatment of severe or debilitating insomnia. Brotizolam is an extremely potent drug and it is rapidly eliminated with an average half-life of 4.4 hours (range 3.6 - 7.9 hours). Brotizolam is not approved for sale in the UK, United States or Canada. It is approved for sale in the Netherlands, Germany, Spain, Belgium, Austria, Portugal, Israel, Italy and Japan.

Contaminant Sources

STOFF IDENT Compounds
T3DB toxins
ToxCast & Tox21 Chemicals

Contaminant Type

Bromide Compound
Drug
Organic Compound
Organobromide
Organochloride
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Value	Source
Mederantil	ChEMBL
Lendorm	ChEMBL, MeSH
WE 941	ChEMBL
Europharma brand OF brotizolam	MeSH
Lendormin	MeSH
Sintonal	MeSH
Lindormin	MeSH
promeco Brand OF brotizolam	MeSH

Chemical Formula

C₁₅H₁₀BrClN₄S

Average Molecular Mass

393.689 g/mol

Monoisotopic Mass

391.950 g/mol

CAS Registry Number

57801-81-7

IUPAC Name

4-bromo-7-(2-chlorophenyl)-13-methyl-3-thia-1,8,11,12-tetraazatricyclo[8.3.0.0²,⁶]trideca-2(6),4,7,10,12-pentaene

Traditional Name

brotizolam

SMILES

CC1=NN=C2CN=C(C3=C(SC(Br)=C3)N12)C1=CC=CC=C1Cl

InChI Identifier

InChI=1S/C15H10BrClN4S/c1-8-19-20-13-7-18-14(9-4-2-3-5-11(9)17)10-6-12(16)22-15(10)21(8)13/h2-6H,7H2,1H3

InChI Key

UMSGKTJDUHERQW-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.

Kingdom

Organic compounds

Super Class

Organoheterocyclic compounds

Class

Thienodiazepines

Sub Class

Not Available

Direct Parent

Thienodiazepines

Alternative Parents

Substituents

Thieno-para-diazepine
2,3,5-trisubstituted thiophene
Para-diazepine
Chlorobenzene
Halobenzene
Aryl bromide
Aryl chloride
Aryl halide
Monocyclic benzene moiety
Benzenoid
Thiophene
Heteroaromatic compound
1,2,4-triazole
Azole
Ketimine
Organic 1,3-dipolar compound
Propargyl-type 1,3-dipolar organic compound
Azacycle
Organonitrogen compound
Hydrocarbon derivative
Organopnictogen compound
Imine
Organohalogen compound
Organobromide
Organic nitrogen compound
Organochloride
Aromatic heteropolycyclic compound

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

Not Available

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Not Available

Biological Roles

Not Available

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	211-213°C
Boiling Point	Not Available
Solubility	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.058 g/L	ALOGPS
logP	3.28	ALOGPS
logP	2.68	ChemAxon
logS	-3.8	ALOGPS
pKa (Strongest Acidic)	18.49	ChemAxon
pKa (Strongest Basic)	3.9	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	3	ChemAxon
Hydrogen Donor Count	0	ChemAxon
Polar Surface Area	43.07 Å²	ChemAxon
Rotatable Bond Count	1	ChemAxon
Refractivity	101.93 m³·mol⁻¹	ChemAxon
Polarizability	34.99 Å³	ChemAxon
Number of Rings	4	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	View
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0006-0019000000-388396f82970a2143ea8	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0gvx-0069000000-4a2a6aefd04937c82f4b	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0a59-0095000000-88e892c4cc10fc966914	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0006-0019000000-064923029f35634b231d	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0006-0009000000-833da840e29e77dbf11d	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0udi-2069000000-c9bfe4b36e310a78b62a	Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-0006-6559000000-7456ba6570cdfa674b63	Spectrum

Toxicity Profile

Route of Exposure

Not Available

Mechanism of Toxicity

Benzodiazepines bind nonspecifically to benzodiazepine receptors BNZ1, which mediates sleep, and BNZ2, which affects affects muscle relaxation, anticonvulsant activity, motor coordination, and memory. As benzodiazepine receptors are thought to be coupled to gamma-aminobutyric acid-A (GABAA) receptors, this enhances the effects of GABA by increasing GABA affinity for the GABA receptor. Binding of the inhibitory neurotransmitter GABA to the site opens the chloride channel, resulting in a hyperpolarized cell membrane that prevents further excitation of the cell.

Metabolism

Not Available

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

Brotizolam is used in the short term treatment of severe or debilitating insomnia.

Minimum Risk Level

Not Available

Health Effects

Not Available

Symptoms

Not Available

Treatment

General supportive measures should be employed, along with intravenous fluids, and an adequate airway maintained. Hypotension may be combated by the use of norepinephrine or metaraminol. Dialysis is of limited value. Flumazenil (Anexate) is a competitive benzodiazepine receptor antagonist that can be used as an antidote for benzodiazepine overdose. In particular, flumazenil is very effective at reversing the CNS depression associated with benzodiazepines but is less effective at reversing respiratory depression. Its use, however, is controversial as it has numerous contraindications. It is contraindicated in patients who are on long-term benzodiazepines, those who have ingested a substance that lowers the seizure threshold, or in patients who have tachycardia or a history of seizures. As a general rule, medical observation and supportive care are the mainstay of treatment of benzodiazepine overdose. Although benzodiazepines are absorbed by activated charcoal, gastric decontamination with activated charcoal is not beneficial in pure benzodiazepine overdose as the risk of adverse effects often outweigh any potential benefit from the procedure. It is recommended only if benzodiazepines have been taken in combination with other drugs that may benefit from decontamination. Gastric lavage (stomach pumping) or whole bowel irrigation are also not recommended.

Concentrations

Not Available

External Links

DrugBank ID

DB09017

HMDB ID

Not Available

FooDB ID

Not Available

Phenol Explorer ID

Not Available

KNApSAcK ID

Not Available

BiGG ID

Not Available

BioCyc ID

Not Available

METLIN ID

Not Available

PDB ID

Not Available

Wikipedia Link

Brotizolam

Chemspider ID

Not Available

ChEBI ID

Not Available

PubChem Compound ID

2451

Kegg Compound ID

Not Available

YMDB ID

Not Available

ECMDB ID

Not Available

References

Synthesis Reference

U.S. Patent 4,094,984.

MSDS

Not Available

General References

Not Available

Brotizolam (CHEM003533)

Structure for CHEM003533: Brotizolam