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
식별자 및 물리적 특성
| CAS No. | 78755-81-4 |
|---|---|
| 분자식 | C15H14FN3O3 |
| 평균 분자량 | 303.29 g/mol |
| 단동위원소 질량 | 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 |
화학 및 물리적 성질
| XLogP | 1 |
|---|---|
| 극성 표면적 | 64.4 |
| 수소 결합 공여자 수 | 0 |
| 수소 결합 수용자 수 | 5 |
| 회전 가능 결합 수 | 3 |
| 무거운 원자 수 | 22 |
| 형식 전하 | 0 |
| 복잡도 | 461 |
| 의약품 | Pharmaceuticals -> Listed in ZINC15Pharmaceuticals -> Various |
| LogP(분배 계수) | 1.91.26 |
| 용해도 | 1.04e+00 g/LDMSO에서 25mM까지 용해 가능 |
| Human Drugs | Breast FeedingLactationMilk, HumanAntidotesGABA ModulatorsBenzodiazepinesFDA approved drugs -> Active ingredient |
| 녹는점 | 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)] |
| 끓는 점 | 528.0±50.0 °C(Predicted) |
| 밀도 | 1.39±0.1 g/cm3(Predicted) |
| 저장 조건 | Sealed in dry,2-8°C |
| 물리적 상태 | 고체 |
| pKa(산도 계수) | 0.86±0.20(Predicted) |
| 색상 | 하얀색 |
| 용해도 | 128mg/L |
| Merck | 14,4135 |
| 안정성 | 제공된 대로 구매일로부터 2년 동안 안정적입니다. DMSO 용액은 -20°C에서 최대 3개월 동안 보관할 수 있습니다. |
| 주요 응용 | 의약품(소분자) |
| 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 |
| NIST | Flumazenil(78755-81-4) |
화학적 성질
Flumazenil is a white to off-white crystalline compound with an octanol:buffer partition coefficient of 14 to 1 at pH 7.4. It is insoluble in water but slightly soluble in acidic aqueous solutions.
안전 및 규제
| GHS 분류 | 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%) |
| 유해 작용 | Serious Adverse Events |
| 독성 요약 | 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 |
| 수질 위해 등급(WGK) | 2 |
| RTECS 번호 | NI2922170 |
| 독성 | LD50 in mice, rats (mg/kg): 4000, 1360 i.p.4300, 6000 orally (Hunkeler) |
| 관세 코드 | 2933997500 |
| 위험 문구(R) | 36/37/38 |
| 위험 표시 | Xi |
| 안전 문구(S) | 26-27-36/37/39 |
| 저장 분류 | 11 - Combustible Solids |
용도
개요
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.
용도
Flumazenil is an imidazodiazepine which selectively blocks the central effects of classic benzodiazepines. It is used as benzodiazepine antagonist sedation reversal drug.
제조 및 합성 방법
제조 방법
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.