ethyl 12-fluoro-8-methyl-9-oxo-2,4,8-triazatricyclo[8.4.0.0^{2,6}]tetradeca-1(10),3,5,11,13-pentaene-5-carboxylate

• ChemBase编号: 1075
• 分子式: C15H14FN3O3
• 平均质量: 303.2883632
• 单一同位素质量: 303.10191954
• SMILES: Fc1cc2c(n3c(CN(C2=O)C)c(nc3)C(=O)OCC)cc1
• Canonical SMILES: CCOC(=O)c1ncn2c1CN(C)C(=O)c1c2ccc(c1)F
• InChI: InChI=1S/C15H14FN3O3/c1-3-22-15(21)13-12-7-18(2)14(20)10-6-9(16)4-5-11(10)19(12)8-17-13/h4-6,8H,3,7H2,1-2H3
• InChIKey: OFBIFZUFASYYRE-UHFFFAOYSA-N

名称和登记号

名称

• IUPAC标准名: ethyl 12-fluoro-8-methyl-9-oxo-2,4,8-triazatricyclo[8.4.0.0^{2,6}]tetradeca-1(10),3,5,11,13-pentaene-5-carboxylate; ethyl 12-fluoro-8-methyl-9-oxo-2,4,8-triazatricyclo[8.4.0.0^2,^6]tetradeca-1(10),3,5,11,13-pentaene-5-carboxylate; ethyl 12-fluoro-8-methyl-9-oxo-2,4,8-triazatricyclo[8.4.0.0^{2,6}]tetradeca-1(14),3,5,10,12-pentaene-5-carboxylate; ethyl 12-fluoro-8-methyl-9-oxo-2,4,8-triazatricyclo[8.4.0.0^2,^6]tetradeca-1(14),3,5,10,12-pentaene-5-carboxylate
• IUPAC传统名: flumazenil
• 商标名: Anexate; Flumazepil; Lanexat; Mazicon; Romazicon
• 别名: Flumazenilo [Spanish]; Flumazenilum [Latin]; Flumazenil; 8-Fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylic Acid Ethyl Ester; Flumenazil; Ro 15-1788/000; Ro 151788; Ro 1722; Ro 41-8157; Romazicon; Flumazepil; Ro 15-1788; Anexate; Lanexat; Mazicon; Ro15-1788; Flumazenil

登记号

• CAS号: 78755-81-4
• MDL号: MFCD00242764
• PubChem SID: 160964538; 46507438; 24278437
• PubChem CID: 3373

理论计算性质

JChem

• 质子受体: 3
• 质子供体: 0
• LogD (pH = 5.5): 0.32545927
• LogD (pH = 7.4): 0.32786918
• Log P: 0.3279
• 摩尔折射率: 87.9286 cm^3
• 极化性: 29.21609 Å^3
• 极化表面积: 64.43 Å^2
• 可自由旋转的化学键: 3
• 里宾斯基五规则: true

ALOGPS 2.1

• Log P: 1.54
• LOG S: -2.46
• 溶解度: 1.04e+00 g/l

分子性质

理化性质

• 溶解度: 128 mg/L; Chloroform; Methanol
• 外观: white solid; White Solid
• 熔点: 191-193°C
• 疏水性(logP): 1.9

安全信息

• 保存条件: -20°C; Refrigerator
• RTECS编号: NI2922170
• 德国WGK号: 2
• 个人保护装置: Eyeshields, Gloves, type N95 (US), type P1 (EN143) respirator filter
• 保存温度: 2-8°C

药理学性质

• 作用靶点: GABA transporter
• 相关基因信息: human ... BZRAP1(9256), GABRA1(2554), GABRA2(2555), GABRA3(2556), GABRA5(2558), GABRA6(2559), GABRG2(2566)rat ... Gabra2(29706), Gabrg1(140674)

产品相关信息

• 纯度: >99% (HPLC)
• 成盐信息: Free Base

详细说明

DrugBank - DB01205

• Drug Groups: approved
• Description: Fumazenil is an imidazobenzodiazepine derivative and a potent benzodiazepine receptor antagonist that competitively inhibits the activity at the benzodiazepine recognition site on the GABA/benzodiazepine receptor complex, thereby reversing the effects of benzodiazepine on the central nervous system.
• Indication: For the complete or partial reversal of the sedative effects of benzodiazepines in cases where general anesthesia has been induced and/or maintained with benzodiazepines, and where sedation has been produced with benzodiazepines for diagnostic and therapeutic procedures. Also for the management of benzodiazepine overdose as an adjunct for appropriate supportive and symptomatic measures.
• Pharmacology: Flumazenil antagonizes the CNS effects produced by benzodiazepines, but does not antagonize the central nervous system effects of drugs affecting GABA-ergic neurons by means other than the benzodiazepine receptor (including ethanol, barbiturates, or general anesthetics) and does not reverse the effects of opioids.
• Toxicity: In clinical studies, most adverse reactions to flumazenil were an extension of the pharmacologic effects of the drug in reversing benzodiazepine effects.
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic. Flumazenil is completely (99%) metabolized. The major metabolites of flumazenil identified in urine are the de-ethylated free acid and its glucuronide conjugate.
• Half Life: Initial distribution half-life is 4 to 11 minutes and the terminal half-life is 40 to 80 minutes. Prolongation of the half-life to 1.3 hours in patients with moderate hepatic impairment and 2.4 hours in severely impaired patients. Compared to adults, the elimination half-life in pediatric patients was more variable, averaging 40 minutes (range: 20 to 75 minutes).
• Protein Binding: Protein binding is approximately 50%, mostly (66%) to albumin. Protein binding is reduced in patients with hepatic cirrhosis.
• Elimination: Flumazenil is completely (99%) metabolized. Elimination of radiolabeled drug is essentially complete within 72 hours, with 90% to 95% of the radioactivity appearing in urine and 5% to 10% in the feces.
• Distribution: * 0.9 to 1.1 L/kg
• Clearance: * 1 L/hr/kg [healthy volunteers receiving a 5-minute infusion of a total of 1 mg]
• References: Ngo AS, Anthony CR, Samuel M, Wong E, Ponampalam R: Should a benzodiazepine antagonist be used in unconscious patients presenting to the emergency department? Resuscitation. 2007 Jul;74(1):27-37. Epub 2007 Feb 15. [Pubmed] ; Olkkola KT, Ahonen J: Midazolam and other benzodiazepines. Handb Exp Pharmacol. 2008;(182):335-60. [Pubmed] ; Maeda S, Miyawaki T, Higuchi H, Shimada M: Effect of flumazenil on disturbance of equilibrium function induced by midazolam. Anesth Prog. 2008 Fall;55(3):73-7. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

Selleck Chemicals - S1332

Research Area: Neurological Disease
Biological Activity:
Flumazenil, an imidazobenzodiazepine derivative, antagonizes the actions of benzodiazepines on the central nervous system. Flumazenil competitively inhibits the activity at the benzodiazepine recognition site on the GABA/benzodiazepine receptor complex. Flumazenil is a weak partial agonist in some animal models of activity, but has little or no agonist activity in humans. [1]

Sigma Aldrich - F6300

Biochem/physiol Actions
Highly specific benzodiazepine receptor antagonist.
Other Notes
Tandem Mass Spectrometry data independently generated by Scripps Center for Metabolomics is available to view or download in PDF. F6300.pdf Tested metabolites are featured on Scripps Center for Metabolomics METLIN Metabolite Database. To learn more, visit sigma.com/metlin.

Toronto Research Chemicals - F500450

Imidazodiazepine which selectively blocks the central effects of classic benzodiazepines. It is used as benzodiazepine antagonist.

参考文献

• Olkkola KT, Ahonen J: Midazolam and other benzodiazepines. Handb Exp Pharmacol. 2008;(182):335-60. Pubmed
• Ngo AS, Anthony CR, Samuel M, Wong E, Ponampalam R: Should a benzodiazepine antagonist be used in unconscious patients presenting to the emergency department? Resuscitation. 2007 Jul;74(1):27-37. Epub 2007 Feb 15. Pubmed
• Maeda S, Miyawaki T, Higuchi H, Shimada M: Effect of flumazenil on disturbance of equilibrium function induced by midazolam. Anesth Prog. 2008 Fall;55(3):73-7. Pubmed
• http://en.wikipedia.org/wiki/Flumazenil
• Hunkeler, W., et al.: Nature, 290, 514 (1981)
• Pole, P., et al.: Arch. Pharmacol., 316, 317 (1981)
• Timm, U., et al.: Arzneim.-Forsch., 33, 358 (1981)