기본 정보
- 표준 SMILES
CCOC(=O)c1ncn2c1CN(C)C(=O)c1cc(F)ccc1-2- InChIKey
OFBIFZUFASYYRE-UHFFFAOYSA-N- 분자식
- C15H14FN3O3
- 평균 분자량
- 303.29 g/mol
- 단동위원소 질량
- 303.10191953
개요
Flumazenil is an organic heterotricyclic compound that is 5,6-dihydro-4H-imidazo[1,5-a][1,4]benzodiazepine which is substituted at positions 3, 5, 6, and 8 by ethoxycarbonyl, methyl, oxo, and fluoro groups, respectively. It is used as an antidote to benzodiazepine overdose. It has a role as a GABA antagonist and an antidote to benzodiazepine poisoning. It is an imidazobenzodiazepine, an ethyl ester and an organofluorine compound.
이름 및 식별자
- 우선 이름
- Flumazenil
- IUPAC
- ethyl 8-fluoro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate
- 영어명
- Flumazenil
- 분자식
- C15H14FN3O3
- 분자량
- 303.29
이름 및 동의어
이름 더 보기
데이터베이스 식별자
- CAS
78755-81-4- PubChem CID
- 3373
- DTXSID
DTXSID2023064- ChEMBL
CHEMBL407- ChEBI
CHEBI:5103- UNII
- 40P7XK9392
- EC Number
- 616-650-9
- Nikkaji
- J23.594F
물성
구조 계산 물성
- XLogP
- 1
- 극성 표면적
- 64.4 Ų
- 수소 결합 공여자 수
- 0
- 수소 결합 수용자 수
- 5
- 회전 가능 결합 수
- 3
- 무거운 원자 수
- 22
- 형식 전하
- 0
- 복잡도
- 461
실험 및 물리화학적 성질
Drugs
Pharmaceuticals -> Listed in ZINC15
Pharmaceuticals -> Various
LogP
1.9
1.26
Human Drugs
Breast Feeding; Lactation; Milk, Human; Antidotes; GABA Modulators; Benzodiazepines
FDA approved drugs -> Active ingredient
FDA approved drugs -> Active ingredient
Melting Point
201-203 °C
201 - 203 °C
Collision Cross Section
164.31 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]
165.6 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]
165.8 Ų [M+H]+ [CCS Type: TW; Method: Major Mix IMS/Tof Calibration Kit (Waters)]
물리화학적 성질
- 녹는점
- 201 · 201-203°C
- 끓는 점
- 528 · 528.0±50.0 °C(Predicted)
- 밀도
- 1.39 · 1.39±0.1 g/cm3(Predicted)
- 저장 조건
- 2 · Sealed in dry,2-8°C
- 용해도
- 25 mM까지 · DMSO에서 25mM까지 용해 가능
- 물리적 상태
- 고체
- 산도 계수 (pKa)
- 0.86 · 0.86±0.20(Predicted)
- 색상
- 하얀색
- 수용성
- 128 mg/L · 128mg/L
- Merck
- 14 · 14,4135
- 안정성
- 2 · 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
GHS Classification
This chemical does not meet GHS hazard criteria for 20% (1 of 5) of reports.
Warning
H302 (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.
유해성 정보
독성 정보
Drug Induced Liver Injury
Drug Induced Liver Injury Rank (DILIrank 2.0)
Flumazenil
vNo-DILI-concern
0
No match
DOI:10.1016/j.drudis.2016.02.015
안전 데이터
- wgk
- 2
- rtecs
- NI2922170
- 독성
- LD50 in mice, rats (mg/kg): 4000, 1360 i.p.; 4300, 6000 orally (Hunkeler)
- HS 번호
- 2933997500
- risk_code
- 36/37/38
- hazard_code
- Xi
- safety_code
- 26-27-36/37/39
- 스토리지 클래스
- 11 - Combustible Solids
화학 및 산업
약리 정보
ATC Code
V - Various
QV - Various
Pharmacodynamics
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.
Mechanism of Action
Flumazenil, an imidazobenzodiazepine derivative, is a benzodiazepine antagonist. It competitively inhibits the benzodiazepine binding 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 man.
Biological 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).
FDA Pharmacological Classification
40P7XK9392
FLUMAZENIL
Established Pharmacologic Class [EPC] - Benzodiazepine Antagonist
Flumazenil is a Benzodiazepine Antagonist.
FLUMAZENIL
Benzodiazepine Antagonist [EPC]
MeSH Pharmacological Classification
Agents counteracting or neutralizing the action of POISONS.
Substances that do not act as agonists or antagonists but do affect the GAMMA-AMINOBUTYRIC ACID receptor-ionophore complex. GABA-A receptors (RECEPTORS, GABA-A) appear to have at least three allosteric sites at which modulators act: a site at which BENZODIAZEPINES act by increasing the opening frequency of GAMMA-AMINOBUTYRIC ACID-activated chloride channels; a site at which BARBITURATES act to prolong the duration of channel opening; and a site at which some steroids may act. GENERAL ANESTHETICS probably act at least partly by potentiating GABAergic responses, but they are not included here.
Absorption, Distribution and Excretion
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.
0.9 to 1.1 L/kg
1 L/hr/kg [healthy volunteers receiving a 5-minute infusion of a total of 1 mg]
응용 분야
개요Flumazenil 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.
용도Flumazenil is an imidazodiazepine which selectively blocks the central effects of classic benzodiazepines. It is used as benzodiazepine antagonist sedation reversal drug.
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.
상·하류 제품 정보
상류 원료
하류 제품
공급사50 곳
추가 설명
정의ChEBI: Flumazenil is an organic heterotricyclic compound that is 5,6-dihydro-4H-imidazo[1,5-a][1,4]benzodiazepine which is substituted at positions 3, 5, 6, and 8 by ethoxycarbonyl, methyl, oxo, and fluoro groups, respectively. It is used as an antidote to benzodiazepine overdose. It has a role as a GABA antagonist and an antidote to benzodiazepine poisoning. It is an ethyl ester, an organofluorine compound and an imidazobenzodiazepine.
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