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 ID: 1075
• Molecular Formular: C15H14FN3O3
• Molecular Mass: 303.2883632
• Monoisotopic Mass: 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

NAMES AND DATABASE IDS

Names

• IUPAC name: 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 Traditional name: flumazenil
• Brand Name: Anexate; Flumazepil; Lanexat; Mazicon; Romazicon
• Synonyms: 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

Database IDs

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

CALCULATED PROPERTIES

JChem

• H Acceptors: 3
• H Donor: 0
• LogD (pH = 5.5): 0.32545927
• LogD (pH = 7.4): 0.32786918
• Log P: 0.3279
• Molar Refractivity: 87.9286 cm^3
• Polarizability: 29.21609 Å^3
• Polar Surface Area: 64.43 Å^2
• Rotatable Bonds: 3
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 1.54
• LOG S: -2.46
• Solubility (Water): 1.04e+00 g/l

PROPERTIES

Physical Property

• Solubility: 128 mg/L; Chloroform; Methanol
• Apperance: white solid; White Solid
• Melting Point: 191-193°C
• Hydrophobicity(logP): 1.9

Safety Information

• Storage Condition: -20°C; Refrigerator
• RTECS: NI2922170
• German water hazard class: 2
• Personal Protective Equipment: Eyeshields, Gloves, type N95 (US), type P1 (EN143) respirator filter
• Storage Temperature: 2-8°C

Pharmacology Properties

• Target: GABA transporter
• Gene Information: human ... BZRAP1(9256), GABRA1(2554), GABRA2(2555), GABRA3(2556), GABRA5(2558), GABRA6(2559), GABRG2(2566)rat ... Gabra2(29706), Gabrg1(140674)

Product Information

• Purity: >99% (HPLC)
• Salt Data: Free Base

DETAILS

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.

REFERENCES

• 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)