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

• ChemBase编号: 1329
• 分子式: C16H12FN3O3
• 平均质量: 313.2831832
• 单一同位素质量: 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

名称和登记号

名称

• IUPAC标准名: 5-(2-fluorophenyl)-1-methyl-7-nitro-2,3-dihydro-1H-1,4-benzodiazepin-2-one
• IUPAC传统名: primun; fluniβ
• 商标名: Roipnol; Narcozep; Primun; Rohypnol
• 别名: 氟硝西泮; 氟硝西泮 溶液; 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

登记号

• CAS号: 1622-62-4
• EC号: 200-659-6; 216-597-8
• MDL号: MFCD00057906
• PubChem SID: 160964789; 46504553; 24894993
• PubChem CID: 3380
• ATC码: N05CD03
• CHEMBL: 13280
• Chemspider ID: 3263
• DrugBank ID: DB01544
• KEGG ID: D01230
• 美国药典/FDA物质标识码: 620X0222FQ
• 维基百科标题: Flunitrazepam

理论计算性质

JChem

• 质子受体: 4
• 质子供体: 0
• LogD (pH = 5.5): 2.55466
• LogD (pH = 7.4): 2.554727
• Log P: 2.554728
• 摩尔折射率: 82.5482 cm^3
• 极化性: 30.054867 Å^3
• 极化表面积: 78.49 Å^2
• 可自由旋转的化学键: 2
• 里宾斯基五规则: true

ALOGPS 2.1

• Log P: 2.2
• LOG S: -4.56
• 溶解度: 8.58e-03 g/l

分子性质

理化性质

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

安全信息

• RTECS编号: DF2385000
• 欧盟危险性物质标志: 有害性(Harmful) (Xn)
• 德国WGK号: 2
• 危险公开号: 22-36
• 安全公开号: 26-36
• GHS危险品标识: GHS07
• GHS警示词: Warning
• GHS危险声明: H302-H319
• GHS警示性声明: P305 + P351 + P338
• 个人保护装置: dust mask type N95 (US), Eyeshields, Faceshields, Gloves
• 毒品管制信息: USDEA Schedule IV; Home Office Schedule 3; psychotrope; kontrollierte Droge in Deutschland; regulated under CDSA - not available from Sigma-Aldrich Canada

药理学性质

• 给药途径: Oral
• 生物利用度: 50% (suppository); 64–77% (oral)
• 排泄: Renal
• 半衰期: 18–26 hours
• 代谢: Hepatic
• 法定药品分级: CD No Reg POM (UK); III (International); S8 (Australia); Schedule IV (US)
• 妊娠期药物分类: C (Australia)
• 相关基因信息: human ... GABRA1(2554), GABRA2(2555), GABRA3(2556), GABRA5(2558), GABRA6(2559)rat ... Gabra2(29706)

详细说明

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).

参考文献

• 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)