Flumazenil
Romazicon · FMZ · ethyl 8-fluoro-5-Methyl-6-oxo-5,6-dihydro-4H-benzo[f]iMidazo[1,5-a][1,4]diazepine-3-carboxylate · YM-684 · Lanexat · Mazicon · Ro 1722 · ANEXATE
Identifikatoren & physikalische Daten
| CAS No. | 78755-81-4 |
|---|---|
| Summenformel | C15H14FN3O3 |
| Durchschnittliche Molmasse | 303,29 g/mol |
| Monoisotopische Masse | 303,10191953 g/mol |
| SMILES | CCOC(=O)c1ncn2c1CN(C)C(=O)c1cc(F)ccc1-2 |
| InChIKey | OFBIFZUFASYYRE-UHFFFAOYSA-N |
| PubChem CID | 3373 |
| ChEMBL | CHEMBL407 |
| ChEBI | CHEBI:5103 |
| EC No. | 616-650-9 |
| DTXSID | DTXSID2023064 |
Chemische & physikalische Eigenschaften
| XLogP | 1 |
|---|---|
| Polarare Oberfläche (TPSA) | 64,4 |
| H-Brücken-Donoren | 0 |
| H-Brücken-Akzeptoren | 5 |
| Frei drehbare Bindungen | 3 |
| Schwere Atome | 22 |
| Formalladung | 0 |
| Komplexität | 461 |
| Arzneimittel | Pharmaceuticals -> Listed in ZINC15Pharmaceuticals -> Various |
| LogP (Verteilungskoeffizient) | 1.91.26 |
| Löslichkeit | 1.04e+00 g/LSoluble in DMSO to 25mM128 mg/L |
| Human Drugs | Breast FeedingLactationMilk, HumanAntidotesGABA ModulatorsBenzodiazepinesFDA approved drugs -> Active ingredient |
| Schmelzpunkt | 201-203 °C201 - 203 °C201-203°C |
| Physical Description | Solid |
| Collision Cross Section | 164.31 Ų [M+H]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards]165.6 Ų [M+H]+ [CCS Type: TW165.8 Ų [M+H]+ [CCS Type: TWMethod: Major Mix IMS/Tof Calibration Kit (Waters)] |
| Siedepunkt | 528.0±50.0 °C(Predicted) |
| Dichte | 1.39±0.1 g/cm3(Predicted) |
| Lagerbedingungen | Sealed in dry,2-8°C |
| Aggregatzustand | solid |
| pKa (Säurekonstante) | 0.86±0.20(Predicted) |
| Farbe | white |
| Merck | 14,4135 |
| Stabilität | Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months. |
| Hauptanwendungen | pharmaceutical (small molecule) |
| 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 |
| SMILES | N12C=NC(C(OCC)=O)=C1CN(C)C(=O)C1=CC(F)=CC=C12 |
| CAS Datenbank | 78755-81-4(CAS DataBase Reference) |
| NIST chemische Informationen | Flumazenil(78755-81-4) |
Sicherheit & Vorschriften
| GHS-Einstufung | This chemical does not meet GHS hazard criteria for 20% (1 of 5) of reports.WarningH302 (80%): Harmful if swallowed [Warning Acute toxicity, oral]P261, P264, P270, P271, P301+P317, P304+P340, P317, P330, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 5 reports by companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
|---|---|
| Hazard Classes and Categories | Acute Tox. 4 (80%) |
| Unerwünschte Wirkungen | Serious Adverse Events |
| Toxizitätsübersicht | Flumazenil has some associations with the precipitation of seizures in patients with benzodiazepine dependency with a history of seizures. However, flumazenil overdose is extremely rare. |
| Drug Induced Liver Injury | Drug Induced Liver Injury Rank (DILIrank 2.0)FlumazenilvNo-DILI-concernNo matchDOI:10.1016/j.drudis.2016.02.015 |
| Effects During Pregnancy and Lactation | ◉ Summary of Use during Lactation |
| Wassergefährdungsklasse (WGK) | 2 |
| Zollcode | 2933997500 |
| RTECS-Nr. | NI2922170 |
| R-Sätze (R) | 36/37/38 |
| Toxizität | LD50 in mice, rats (mg/kg): 4000, 1360 i.p.4300, 6000 orally (Hunkeler) |
| Gefahrensymbole | Xi |
| Sicherheitshinweise (S) | 26-27-36/37/39 |
| Lagerklasse | 11 - Combustible Solids |
Anwendungen & Verwendung
Beschreibung
Flumazenil is a benzodiazepine antagonist useful as a fast-acting antidote in the treatment of benzodiazepine intoxication, and in reversing the central sedative effects of benzodiazepines during anesthesia.
Verwenden
Flumazenil is an imidazodiazepine which selectively blocks the central effects of classic benzodiazepines. It is used as benzodiazepine antagonist sedation reversal drug.
Herstellung & Synthese
synthetische
The Synthesis of FlumazenilStarting with 4-fluoroaniline (15) the isatin 17 is synthesized via the Sandmeyer synthesis; isatin is then oxidized with peracetic acid to the isatoic anhydride 18. Reaction with sarcosine in DMF leads to the benzodiazepine-2,5-dione 19. This is converted to the iminochloride by reaction with POCI3 . In the key step the imidazoester is built up by reaction with deprotonated ethyl isocyanoacetate [8]. Since ethyl isocyanoacetate is not very stable, an alternative synthesis based on the synthesis of midazolam was developed for large scale-production. Tnthis synthesis diethylmalonate is used. The diester 21 is then transformed to the monoester 22 hy deethoxycarbonylation. Nitrosation and catalytic reduction lead to the amino compound 23. The final carbon atom is introduced by reaction with the orthoester.