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

• ChemBase编号: 71
• 分子式: C15H10Cl2N2O2
• 平均质量: 321.1581
• 单一同位素质量: 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

名称和登记号

名称

• IUPAC标准名: 7-chloro-5-(2-chlorophenyl)-3-hydroxy-2,3-dihydro-1H-1,4-benzodiazepin-2-one
• IUPAC传统名: @lorazepam; lorazepam
• 商标名: 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
• 别名: 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

登记号

• CAS号: 846-49-1
• EC号: 212-687-6
• MDL号: MFCD00063406
• PubChem SID: 24896291; 160963534; 46508468
• PubChem CID: 3958
• ATC码: N05BA06
• CHEMBL: 580
• Chemspider ID: 3821
• DrugBank ID: DB00186
• KEGG ID: D00365
• 美国药典/FDA物质标识码: O26FZP769L
• 维基百科标题: Lorazepam
• Medline Plus: a682053

理论计算性质

JChem

• Acid pKa: 10.606301
• 质子受体: 3
• 质子供体: 2
• LogD (pH = 5.5): 3.527322
• LogD (pH = 7.4): 3.527058
• Log P: 3.5273254
• 摩尔折射率: 82.6992 cm^3
• 极化性: 31.031853 Å^3
• 极化表面积: 61.69 Å^2
• 可自由旋转的化学键: 1
• 里宾斯基五规则: true

ALOGPS 2.1

• Log P: 2.98
• LOG S: -4.26
• 溶解度: 1.76e-02 g/l

分子性质

理化性质

• 溶解度: 0.08 mg/mL
• 疏水性(logP): 3.5

安全信息

• RTECS编号: DF0350000
• 欧盟危险性物质标志: 有害性(Harmful) (Xn)
• 德国WGK号: 3
• 危险公开号: 63
• 安全公开号: 36/37
• GHS危险品标识: GHS08
• GHS警示词: Warning
• GHS危险声明: H361
• GHS警示性声明: P281
• 个人保护装置: 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
• 毒品管制信息: USDEA Schedule IV; Home Office Schedule 4.1; psychotrope; kontrollierte Droge in Deutschland; regulated under CDSA - not available from Sigma-Aldrich Canada

药理学性质

• 给药途径: Oral, intramuscular, intravenous, sublingual, and transdermal
• 生物利用度: 85% of oral dose
• 排泄: Renal
• 半衰期: 9–16 hours
• 代谢: Hepatic glucuronidation
• 法定药品分级: CD (Benz) POM (UK); Schedule IV (Canada); Schedule IV (US)
• 妊娠期药物分类: D (US)

详细说明

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.

参考文献

• 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