7-chloro-5-(2-chlorophenyl)-3-hydroxy-2,3-dihydro-1H-1,4-benzodiazepin-2-one

• ChemBase ID: 71
• Molecular Formular: C15H10Cl2N2O2
• Molecular Mass: 321.1581
• Monoisotopic Mass: 320.01193293
• SMILES: Clc1cc2C(=NC(O)C(=O)Nc2cc1)c1c(Cl)cccc1
• Canonical SMILES: Clc1ccc2c(c1)C(=NC(C(=O)N2)O)c1ccccc1Cl
• InChI: InChI=1S/C15H10Cl2N2O2/c16-8-5-6-12-10(7-8)13(19-15(21)14(20)18-12)9-3-1-2-4-11(9)17/h1-7,15,21H,(H,18,20)
• InChIKey: DIWRORZWFLOCLC-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 7-chloro-5-(2-chlorophenyl)-3-hydroxy-2,3-dihydro-1H-1,4-benzodiazepin-2-one
• IUPAC Traditional name: @lorazepam; lorazepam
• Brand Name: Almazine; Alzapam; Anxiedin; Aplacassee; Ativan; Bonatranquan; Delormetazepam; Emotival; Idalprem; Lorabenz; Lorax; Loraz; Lorazepam Intensol; Lorsilan; Pro Dorm; Psicopax; Punktyl; Quait; Securit; Sedatival; Sedazin; Somagerol; Tavor; Temesta; Wypax; Ativan and others
• Synonyms: 7-Chloro-5-(2-chlorophenyl)-1,3-dihydro-3-hydroxy-2H-1,4-benzodiazepin-2-one; (±)-Lorazepam; (+/-)-Lorazepam; L-Lorazepam Acetate; O-Chlorooxazepam; O-Chloroxazepam; Lorazepam

Database IDs

• CAS Number: 846-49-1
• EC Number: 212-687-6
• MDL Number: MFCD00063406
• PubChem SID: 46508468; 24896291; 160963534
• PubChem CID: 3958
• ATC CODE: N05BA06
• CHEMBL: 580
• Chemspider ID: 3821
• DrugBank ID: DB00186
• KEGG ID: D00365
• Unique Ingredient Identifier: O26FZP769L
• Wikipedia Title: Lorazepam
• Medline Plus: a682053

CALCULATED PROPERTIES

JChem

• Acid pKa: 10.606301
• H Acceptors: 3
• H Donor: 2
• LogD (pH = 5.5): 3.527322
• LogD (pH = 7.4): 3.527058
• Log P: 3.5273254
• Molar Refractivity: 82.6992 cm^3
• Polarizability: 31.031853 Å^3
• Polar Surface Area: 61.69 Å^2
• Rotatable Bonds: 1
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 2.98
• LOG S: -4.26
• Solubility (Water): 1.76e-02 g/l

PROPERTIES

Physical Property

• Solubility: 0.08 mg/mL
• Hydrophobicity(logP): 3.5

Safety Information

• RTECS: DF0350000
• European Hazard Symbols: Harmful (Xn)
• German water hazard class: 3
• Risk Statements: 63
• Safety Statements: 36/37
• GHS Pictograms: GHS08
• GHS Signal Word: Warning
• GHS Hazard statements: H361
• GHS Precautionary statements: P281
• Personal Protective Equipment: Eyeshields, full-face particle respirator type N100 (US), Gloves, respirator cartridge type N100 (US), type P1 (EN143) respirator filter, type P3 (EN 143) respirator cartridges
• Drug Control: USDEA Schedule IV; Home Office Schedule 4.1; psychotrope; kontrollierte Droge in Deutschland; regulated under CDSA - not available from Sigma-Aldrich Canada

Pharmacology Properties

• Admin Routes: Oral, intramuscular, intravenous, sublingual, and transdermal
• Bioavailability: 85% of oral dose
• Excretion: Renal
• Half Life: 9–16 hours
• Metabolism: Hepatic glucuronidation
• Legal Status: CD (Benz) POM (UK); Schedule IV (Canada); Schedule IV (US)
• Pregnancy Category: D (US)

DETAILS

DrugBank - DB00186

• Drug Groups: approved
• Description: A benzodiazepine used as an anti-anxiety agent with few side effects. It also has hypnotic, anticonvulsant, and considerable sedative properties and has been proposed as a preanesthetic agent. [PubChem]
• Indication: For the management of anxiety disorders, and for treatment of status epilepticus.
• Pharmacology: Lorazepam, a benzodiazepine not transformed to active metabolites, is used to treat anxiety, status epilepticus, and for sedation induction and anterograde amnesia.
• Toxicity: Somnolence, confusion, and coma, LD₅₀=3178mg/kg (orally in mice).
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic
• Absorption: Readily absorbed with an absolute bioavailability of 90%.
• Half Life: 12 hours
• Protein Binding: 85%
• Elimination: Lorazepam is rapidly conjugated at its 3-hydroxy group into lorazepam glucuronide which is then excreted in the urine.
• References: Kemper N, Poser W, Poser S: [Benzodiazepine dependence: addiction potential of the benzodiazepines is greater than previously assumed (author's transl)] Dtsch Med Wochenschr. 1980 Dec 5;105(49):1707-12. [Pubmed] ; Lader M: Short-term versus long-term benzodiazepine therapy. Curr Med Res Opin. 1984;8 Suppl 4:120-6. [Pubmed] ; Maltais F, Laberge F, Laviolette M: A randomized, double-blind, placebo-controlled study of lorazepam as premedication for bronchoscopy. Chest. 1996 May;109(5):1195-8. [Pubmed] ; Heisterkamp DV, Cohen PJ: The effect of intravenous premedication with lorazepam (ativan), pentobarbitone or diazepam on recall. Br J Anaesth. 1975 Jan;47(1):79-81. [Pubmed] ; Milligan DW, Howard MR, Judd A: Premedication with lorazepam before bone marrow biopsy. J Clin Pathol. 1987 Jun;40(6):696-8. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

Sigma Aldrich - L1764

Biochem/physiol Actions
Anxiolytic; ligand for the GABAA receptor benzodiazepine modulatory site.
Other Notes
Tandem Mass Spectrometry data independently generated by Scripps Center for Metabolomics is available to view or download in PDF. L1764.pdf Tested metabolites are featured on Scripps Center for Metabolomics METLIN Metabolite Database. To learn more, visit sigma.com/metlin.

REFERENCES

• Kemper N, Poser W, Poser S: [Benzodiazepine dependence: addiction potential of the benzodiazepines is greater than previously assumed (author's transl)] Dtsch Med Wochenschr. 1980 Dec 5;105(49):1707-12. Pubmed
• Lader M: Short-term versus long-term benzodiazepine therapy. Curr Med Res Opin. 1984;8 Suppl 4:120-6. Pubmed
• Maltais F, Laberge F, Laviolette M: A randomized, double-blind, placebo-controlled study of lorazepam as premedication for bronchoscopy. Chest. 1996 May;109(5):1195-8. Pubmed
• Heisterkamp DV, Cohen PJ: The effect of intravenous premedication with lorazepam (ativan), pentobarbitone or diazepam on recall. Br J Anaesth. 1975 Jan;47(1):79-81. Pubmed
• Milligan DW, Howard MR, Judd A: Premedication with lorazepam before bone marrow biopsy. J Clin Pathol. 1987 Jun;40(6):696-8. Pubmed