T3DB: Ethyl loflazepate

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (18)XML

Targets (18)

Record Information

Version

2.0

Creation Date

2014-08-30 21:05:40 UTC

Update Date

2014-12-24 20:26:52 UTC

Accession Number

T3D4568

Identification

Common Name

Ethyl loflazepate

Class

Small Molecule

Description

Ethyl loflazepate (marketed under the brand names Meilax, Ronlax and Victan) is a drug which is a benzodiazepine derivative. It possesses anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant properties. In animal studies it was found to have low toxicity, although in rats evidence of pulmonary phospholipidosis occurred with pulmonary foam cells developing with long-term use of very high doses. Its elimination half-life is 51 hours - 103 hours.

Compound Type

Amide
Amine
Drug
Ester
Ether
Organic Compound
Organochloride
Organofluoride
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
Azutolem
Bigson
Ethyl loflazepic acid
Medetax
Meilax
Ronlax
Sukarnase
Victan

Chemical Formula

C₁₈H₁₄ClFN₂O₃

Average Molecular Mass

360.767 g/mol

Monoisotopic Mass

360.068 g/mol

CAS Registry Number

29177-84-2

IUPAC Name

ethyl 7-chloro-5-(2-fluorophenyl)-2-oxo-2,3-dihydro-1H-1,4-benzodiazepine-3-carboxylate

Traditional Name

ethyl loflazepate

SMILES

CCOC(=O)C1N=C(C2=CC=CC=C2F)C2=C(C=CC(Cl)=C2)N=C1O

InChI Identifier

InChI=1/C18H14ClFN2O3/c1-2-25-18(24)16-17(23)21-14-8-7-10(19)9-12(14)15(22-16)11-5-3-4-6-13(11)20/h3-9,16H,2H2,1H3,(H,21,23)

InChI Key

InChIKey=CUCHJCMWNFEYOM-UHFFFAOYNA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as alpha amino acid esters. These are ester derivatives of alpha amino acids.

Kingdom

Organic compounds

Super Class

Organic acids and derivatives

Class

Carboxylic acids and derivatives

Sub Class

Amino acids, peptides, and analogues

Direct Parent

Alpha amino acid esters

Alternative Parents

Substituents

Alpha-amino acid ester
Benzodiazepine
1,4-benzodiazepine
Fluorobenzene
Halobenzene
Aryl chloride
Aryl fluoride
Aryl halide
Monocyclic benzene moiety
Benzenoid
1,3-dicarbonyl compound
Carboxamide group
Carboxylic acid ester
Secondary carboxylic acid amide
Ketimine
Lactam
Azacycle
Organoheterocyclic compound
Organic 1,3-dipolar compound
Propargyl-type 1,3-dipolar organic compound
Monocarboxylic acid or derivatives
Imine
Organooxygen compound
Organopnictogen compound
Organic oxygen compound
Carbonyl group
Organic nitrogen compound
Hydrocarbon derivative
Organonitrogen compound
Organofluoride
Organic oxide
Organohalogen 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	196°C
Boiling Point	Not Available
Solubility	Not Available
LogP	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.0052 g/L	ALOGPS
logP	3.36	ALOGPS
logP	3.85	ChemAxon
logS	-4.8	ALOGPS
pKa (Strongest Acidic)	9.51	ChemAxon
pKa (Strongest Basic)	-1.4	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	3	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	67.76 Å²	ChemAxon
Rotatable Bond Count	4	ChemAxon
Refractivity	92.41 m³·mol⁻¹	ChemAxon
Polarizability	35.03 Å³	ChemAxon
Number of Rings	3	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-03di-0019000000-709f2c6e1d2bcd811d84	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-02t9-1119000000-d25b4aa73f3205570971	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-00kr-2796000000-9d9a2caec19d41eebb10	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0bt9-1019000000-c8f9c8a13f5c64cb6411	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-01p9-3098000000-d705fb6543b8a4e0085d	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0006-9121000000-0fb98628eaf5c16bd6fd	2016-08-03	View Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-0670-1941000000-427495e16cf17300345d	2014-09-20	View 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

Ethyl loflazepate also produces an active metabolite which is stronger than the parent compound. Ethyl loflazepate was designed to be a prodrug for descarboxyloflazepate, its active metabolite. It is the active metabolite which is responsible for most of the pharmacological effects rather than ethyl loflazepate. The main metabolites of ethyl loflazepate are descarbethoxyloflazepate, loflazepate and 3-hydroxydescarbethoxyloflazepate.[10] Accumulation of the active metabolites of ethyl loflazepate are not affected by those with renal failure or impairment. (Wikipedia)

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

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

Uses/Sources

Ethyl loflazepate possesses anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant properties. (Wikipedia)

Minimum Risk Level

Not Available

Health Effects

Not Available

Symptoms

The symptoms of an overdose of ethyl loflazepate include sleepiness, agitation and ataxia. Hypotonia may also occur in severe cases. These symptoms occur much more frequently and severely in children.[12] Death from therapeutic maintenance doses of ethyl loflazepate taken for 2 – 3 weeks has been reported in 3 elderly patients. The cause of death was asphyxia due to benzodiazepine toxicity. (Wikipedia)

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.

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

DB01545

HMDB ID

Not Available

PubChem Compound ID

3299

ChEMBL ID

Not Available

ChemSpider ID

3183

KEGG ID

Not Available

UniProt ID

Not Available

OMIM ID

ChEBI ID

Not Available

BioCyc ID

Not Available

CTD ID

Not Available

Stitch ID

Not Available

PDB ID

Not Available

ACToR ID

Not Available

Wikipedia Link

Ethyl_loflazepate

References

Synthesis Reference

British Patent 1,538,165.

MSDS

Not Available

General References

Not Available

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. Gamma-aminobutyric acid receptor subunit alpha-1

General Function:: Inhibitory extracellular ligand-gated ion channel activity
Specific Function:: Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel (By similarity).
Gene Name:: GABRA1
Uniprot ID:: P14867
Molecular Weight:: 51801.395 Da

References

Target Details

2. Gamma-aminobutyric acid receptor subunit alpha-2

General Function:: Inhibitory extracellular ligand-gated ion channel activity
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:: 51325.85 Da

References

Target Details

3. Gamma-aminobutyric acid receptor subunit alpha-3

General Function:: Inhibitory extracellular ligand-gated ion channel activity
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:: 55164.055 Da

References

Target Details

4. Gamma-aminobutyric acid receptor subunit alpha-5

General Function:: Transporter activity
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:: 52145.645 Da

References

Target Details

5. Gamma-aminobutyric acid receptor subunit beta-1

General Function:: Ligand-gated ion channel activity
Specific Function:: Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel (By similarity).
Gene Name:: GABRB1
Uniprot ID:: P18505
Molecular Weight:: 54234.085 Da

References

Target Details

6. Gamma-aminobutyric acid receptor subunit beta-2

General Function:: Inhibitory extracellular ligand-gated ion channel activity
Specific Function:: Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel.
Gene Name:: GABRB2
Uniprot ID:: P47870
Molecular Weight:: 59149.895 Da

References

Target Details

7. Gamma-aminobutyric acid receptor subunit beta-3

General Function:: Gaba-gated chloride ion channel activity
Specific Function:: Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel.
Gene Name:: GABRB3
Uniprot ID:: P28472
Molecular Weight:: 54115.04 Da

References

Target Details

8. Gamma-aminobutyric acid receptor subunit delta

General Function:: Gaba-a receptor activity
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:: GABRD
Uniprot ID:: O14764
Molecular Weight:: 50707.835 Da

References

Target Details

9. Gamma-aminobutyric acid receptor subunit epsilon

General Function:: Inhibitory extracellular ligand-gated ion channel activity
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:: GABRE
Uniprot ID:: P78334
Molecular Weight:: 57971.175 Da

References

Target Details

10. Gamma-aminobutyric acid receptor subunit gamma-1

General Function:: Inhibitory extracellular ligand-gated ion channel activity
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:: GABRG1
Uniprot ID:: Q8N1C3
Molecular Weight:: 53594.49 Da

References

Target Details

11. Gamma-aminobutyric acid receptor subunit gamma-2

General Function:: Inhibitory extracellular ligand-gated ion channel activity
Specific Function:: Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel.
Gene Name:: GABRG2
Uniprot ID:: P18507
Molecular Weight:: 54161.78 Da

References

Target Details

12. Gamma-aminobutyric acid receptor subunit gamma-3

General Function:: Inhibitory extracellular ligand-gated ion channel activity
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:: GABRG3
Uniprot ID:: Q99928
Molecular Weight:: 54288.16 Da

References

Target Details

13. Gamma-aminobutyric acid receptor subunit pi

General Function:: Gaba-a receptor activity
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. In the uterus, the function of the receptor appears to be related to tissue contractility. The binding of this pI subunit with other GABA(A) receptor subunits alters the sensitivity of recombinant receptors to modulatory agents such as pregnanolone.
Gene Name:: GABRP
Uniprot ID:: O00591
Molecular Weight:: 50639.735 Da

References

Target Details

14. Gamma-aminobutyric acid receptor subunit rho-1

General Function:: Gaba-a receptor activity
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. Rho-1 GABA receptor could play a role in retinal neurotransmission.
Gene Name:: GABRR1
Uniprot ID:: P24046
Molecular Weight:: 55882.91 Da

References

Target Details

15. Gamma-aminobutyric acid receptor subunit rho-2

General Function:: Gaba-a receptor activity
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. Rho-2 GABA receptor could play a role in retinal neurotransmission.
Gene Name:: GABRR2
Uniprot ID:: P28476
Molecular Weight:: 54150.41 Da

References

Target Details

16. Gamma-aminobutyric acid receptor subunit rho-3

General Function:: Gaba-a receptor activity
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:: GABRR3
Uniprot ID:: A8MPY1
Molecular Weight:: 54271.1 Da

References

Target Details

17. Translocator protein

General Function:: Cholesterol binding
Specific Function:: Can bind protoporphyrin IX and may play a role in the transport of porphyrins and heme (By similarity). Promotes the transport of cholesterol across mitochondrial membranes and may play a role in lipid metabolism (PubMed:24814875), but its precise physiological role is controversial. It is apparently not required for steroid hormone biosynthesis. Was initially identified as peripheral-type benzodiazepine receptor; can also bind isoquinoline carboxamides (PubMed:1847678).
Gene Name:: TSPO
Uniprot ID:: P30536
Molecular Weight:: 18827.81 Da

References

18. GABA-A receptor (anion channel) (Protein Group)

General Function:: Inhibitory extracellular ligand-gated ion channel activity
Specific Function:: Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel (By similarity).
Included Proteins:: P14867 , P47869 , P34903 , P48169 , P31644 , Q16445 , P18505 , P47870 , P28472 , O14764 , P78334 , Q8N1C3 , P18507 , Q99928 , O00591 , Q9UN88

Ethyl loflazepate (T3D4568)

Structure for T3D4568: Ethyl loflazepate

Targets

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