5-(2-fluorophenyl)-1-methyl-7-nitro-2,3-dihydro-1H-1,4-benzodiazepin-2-one

• ChemBase ID: 1329
• Molecular Formular: C16H12FN3O3
• Molecular Mass: 313.2831832
• Monoisotopic Mass: 313.08626948
• SMILES: Fc1c(C2=NCC(=O)N(c3c2cc([N+](=O)[O-])cc3)C)cccc1
• Canonical SMILES: CN1C(=O)CN=C(c2c1ccc(c2)[N+](=O)[O-])c1ccccc1F
• InChI: InChI=1S/C16H12FN3O3/c1-19-14-7-6-10(20(22)23)8-12(14)16(18-9-15(19)21)11-4-2-3-5-13(11)17/h2-8H,9H2,1H3
• InChIKey: PPTYJKAXVCCBDU-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 5-(2-fluorophenyl)-1-methyl-7-nitro-2,3-dihydro-1H-1,4-benzodiazepin-2-one
• IUPAC Traditional name: primun; fluniβ
• Brand Name: Roipnol; Narcozep; Primun; Rohypnol
• Synonyms: 5-(2-Fluorophenyl)-1,3-dihydro-1-methyl-7-nitro-2H-1,4-benzodiazepin-2-one; 5-(o-Fluorophenyl)-1,3-dihydro-1-methyl-7-nitro-2H-1,4-benzodiazepin-2-one; 5-(2-Fluorophenyl)-1-methyl-7-nitro-1,3-dihydrobenzo[e][1,4]diazepin-2-one; 7-Nitro-1-methyl-5-(2-fluorophenyl)-3H-1,4-benzodiazepin-2(1H)-one; Flunidazepam; Flunipam; Fluridrazepam; Narcozep; Rohypnol; Roipnol; Silece; 5-(2-Fluorophenyl)-1-methyl-7-nitro-3H-1,4-benzodiazepin-2(1H)-one; Ro 5-4200; Flunitrazepam; Flunitrazepam solution; Flunitrazepamum [inn-latin]; Flunitrazepam; 氟硝西泮; 氟硝西泮 溶液

Database IDs

• CAS Number: 1622-62-4
• EC Number: 216-597-8; 200-659-6
• MDL Number: MFCD00057906
• PubChem SID: 46504553; 160964789; 24894993
• PubChem CID: 3380
• ATC CODE: N05CD03
• CHEMBL: 13280
• Chemspider ID: 3263
• DrugBank ID: DB01544
• KEGG ID: D01230
• Unique Ingredient Identifier: 620X0222FQ
• Wikipedia Title: Flunitrazepam

CALCULATED PROPERTIES

JChem

• H Acceptors: 4
• H Donor: 0
• LogD (pH = 5.5): 2.55466
• LogD (pH = 7.4): 2.554727
• Log P: 2.554728
• Molar Refractivity: 82.5482 cm^3
• Polarizability: 30.054867 Å^3
• Polar Surface Area: 78.49 Å^2
• Rotatable Bonds: 2
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 2.2
• LOG S: -4.56
• Solubility (Water): 8.58e-03 g/l

PROPERTIES

Physical Property

• Solubility: 45% (w/v) aq 2-hydroxypropyl-β-cyclodextrin: soluble1 mg/mL; DMF: soluble; ethanol: soluble
• Hydrophobicity(logP): 2.06 [HANSCH,C ET AL. (1995)]

Safety Information

• RTECS: DF2385000
• European Hazard Symbols: Harmful (Xn)
• German water hazard class: 2
• Risk Statements: 22-36
• Safety Statements: 26-36
• GHS Pictograms: GHS07
• GHS Signal Word: Warning
• GHS Hazard statements: H302-H319
• GHS Precautionary statements: P305 + P351 + P338
• Personal Protective Equipment: dust mask type N95 (US), Eyeshields, Faceshields, Gloves
• Drug Control: USDEA Schedule IV; Home Office Schedule 3; psychotrope; kontrollierte Droge in Deutschland; regulated under CDSA - not available from Sigma-Aldrich Canada

Pharmacology Properties

• Admin Routes: Oral
• Bioavailability: 50% (suppository); 64–77% (oral)
• Excretion: Renal
• Half Life: 18–26 hours
• Metabolism: Hepatic
• Legal Status: CD No Reg POM (UK); III (International); S8 (Australia); Schedule IV (US)
• Pregnancy Category: C (Australia)
• Gene Information: human ... GABRA1(2554), GABRA2(2555), GABRA3(2556), GABRA5(2558), GABRA6(2559)rat ... Gabra2(29706)

DETAILS

DrugBank - DB01544

• Drug Groups: illicit; approved
• Description: A benzodiazepine with pharmacologic actions similar to those of diazepam that can cause anterograde amnesia. Some reports indicate that it is used as a date rape drug and suggest that it may precipitate violent behavior. The United States Government has banned the importation of this drug. [PubChem]
• Indication: For short-term treatment of severe insomnias, that are not responsive to other hypnotics.
• Pharmacology: Flunitrazepam is a powerful hypnotic drug that is a benzodiazepine derivative. It has powerful hypnotic, sedative, anxiolytic, and skeletal muscle relaxant properties. The drug is sometimes used as a date rape drug. In the United States, the drug has not been approved by the Food and Drug Administration for medical use, and is considered to be an illegal drug. It has however been approved in the United Kingdom and other countries.
• Toxicity: Symptoms of overdose include confusion, coma, impaired coordination, sleepiness, and slowed reaction time.
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic.
• Absorption: 50% (suppository) and 64-77% (oral)
• Half Life: 18-26 hours
• References: Rickels K: The clinical use of hypnotics: indications for use and the need for a variety of hypnotics. Acta Psychiatr Scand Suppl. 1986;332:132-41. [Pubmed] ; Robertson MD, Drummer OH: Postmortem drug metabolism by bacteria. J Forensic Sci. 1995 May;40(3):382-6. [Pubmed] ; Oelschlager H: [Chemical and pharmacologic aspects of benzodiazepines] Schweiz Rundsch Med Prax. 1989 Jul 4;78(27-28):766-72. [Pubmed] ; Usami N, Yamamoto T, Shintani S, Ishikura S, Higaki Y, Katagiri Y, Hara A: Substrate specificity of human 3(20)alpha-hydroxysteroid dehydrogenase for neurosteroids and its inhibition by benzodiazepines. Biol Pharm Bull. 2002 Apr;25(4):441-5. [Pubmed] ; Tokunaga S, Takeda Y, Shinomiya K, Hirase M, Kamei C: Effects of some H1-antagonists on the sleep-wake cycle in sleep-disturbed rats. J Pharmacol Sci. 2007 Feb;103(2):201-6. Epub 2007 Feb 8. [Pubmed]
• External Links: Wikipedia

Sigma Aldrich - F9261

Biochem/physiol Actions
Hypnotic; anxiolytic; ligand for the GABAA receptor benzodiazepine modulatory site.

Toronto Research Chemicals - F500700

Flunitrazepam is used as an hypnotic. This is a controlled substance (depressant).

REFERENCES

• Rickels K: The clinical use of hypnotics: indications for use and the need for a variety of hypnotics. Acta Psychiatr Scand Suppl. 1986;332:132-41. Pubmed
• Oelschlager H: [Chemical and pharmacologic aspects of benzodiazepines] Schweiz Rundsch Med Prax. 1989 Jul 4;78(27-28):766-72. Pubmed
• Usami N, Yamamoto T, Shintani S, Ishikura S, Higaki Y, Katagiri Y, Hara A: Substrate specificity of human 3(20)alpha-hydroxysteroid dehydrogenase for neurosteroids and its inhibition by benzodiazepines. Biol Pharm Bull. 2002 Apr;25(4):441-5. Pubmed
• Tokunaga S, Takeda Y, Shinomiya K, Hirase M, Kamei C: Effects of some H1-antagonists on the sleep-wake cycle in sleep-disturbed rats. J Pharmacol Sci. 2007 Feb;103(2):201-6. Epub 2007 Feb 8. Pubmed
• Robertson MD, Drummer OH: Postmortem drug metabolism by bacteria. J Forensic Sci. 1995 May;40(3):382-6. Pubmed
• Sternbach, L.H., et al.: J. Med. Chem., 6, 261 (1963)
• Eidelberg, E., et al.: Neurology, 5, 223 (1963)
• Caplan, Y., et al.: J. Anal. Toxicol., 25, 396 (1963)
• Wood, M., et al.: Forensic Sci. Int., 150, 227 (1963)