디플루니살

디플루니살 · DIFLUSINAL · 5-(2,4-Difluorophenyl)-2-hydroxybenzoic acid · 2',4'-Difluoro-4-hydroxy-[1,1'-biphenyl]-3-carboxylic acid · mk647 · Adomal · MK 647 · Dolisal

https://huagongshe.com/ko/chemical/3059

식별자 및 물리적 특성

CAS No.	22494-42-4
분자식	C13H8F2O3
평균 분자량	250.2 g/mol
단동위원소 질량	250.04415056 g/mol
SMILES	O=C(O)c1cc(-c2ccc(F)cc2F)ccc1O
InChIKey	HUPFGZXOMWLGNK-UHFFFAOYSA-N
PubChem CID	3059
ChEMBL	CHEMBL898
ChEBI	CHEBI:39669
EC No.	245-034-9
DTXSID	DTXSID5022932
현지명	디플루니살

화학 및 물리적 성질

XLogP	4.4
극성 표면적	57.5
수소 결합 공여자 수	2
수소 결합 수용자 수	5
회전 가능 결합 수	2
무거운 원자 수	18
형식 전하	0
복잡도	311
의약품	DEA NFLIS-Drug Category -> AnalgesicsPharmaceuticals -> Musculo-skeletal system -> Anti-inflammatory and antirheumatic productsPharmaceuticals -> Listed in ZINC15
LogP(분배 계수)	4.7
용해도	Practically insoluble (14.5 mg/L) at neutral or acidic pH.7.11e-02 g/L물에는 거의 녹지 않으며, 에탄올에는 용해됩니다(96%). 알칼리 수산화물의 묽은 용액에 용해됩니다.
Human Drugs	Breast FeedingLactationMilk, HumanAnalgesic AgentsAnti-inflammatory Agents, NonsteroidalFDA approved drugs -> Active ingredientEMA approved medicines: Human medicine
녹는점	210-211210 - 221 °C207-209C
Physical Description	Solid
Dissociation Constants	3.3
Collision Cross Section	154.55 Å² [M+Na]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards]
끓는 점	386.9±42.0 °C(Predicted)
밀도	1.3505 (estimate)
저장 조건	Keep in dark place,Sealed in dry,Room Temperature
pKa(산도 계수)	pKa 3.3 (H2O I=0.1) (Uncertain)
물리적 상태	Solid
색상	하얀색
용해도	6.186mg/L(24.99ºC)
주요 응용	법의학 및 독성학의약품(소분자)
InChI	InChI=1S/C13H8F2O3/c14-8-2-3-9(11(15)6-8)7-1-4-12(16)10(5-7)13(17)18/h1-6,16H,(H,17,18)
InChIKey	HUPFGZXOMWLGNK-UHFFFAOYSA-N
SMILES	C1(C2=CC=C(F)C=C2F)=CC=C(O)C(C(O)=O)=C1
NIST	Diflunisal(22494-42-4)

화학적 성질

White Solid

안전 및 규제

GHS 분류	WarningH302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]P203, P261, P264, P264+P265, P270, P271, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P318, P319, P321, P330, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 42 reports by companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.
규제 정보	Hazard Traits - Developmental ToxicityReproductive Toxicity
기타 안전 정보	IMAP assessments - [1,1'-Biphenyl]-3-carboxylic acid, 2',4'-difluoro-4-hydroxy-: Human health tier I assessment
Hazard Classes and Categories	Acute Tox. 4 (100%)
Treatment	In the event of overdosage, the stomach should be emptied by inducing vomiting or by gastric lavage, and the patient carefully observed and given symptomatic and supportive treatment. Because of the high degree of protein binding, hemodialysis may not be effective. (L1712)
Hepatotoxicity	Diflunisal therapy is reported to be associated with a low rate of asymptomatic and transient serum aminotransferase elevations, which may resolve even with drug continuation. Marked aminotransferase elevations (>3 fold elevated) occur rarely. Clinically apparent liver injury with jaundice from diflunisal is uncommononly case reports have been published. The clinical and histologic features of diflunisal hepatotoxicity, however, are distinct and resemble an immunoallergic hepatitis, which is quite different from the liver injury that occurs with aspirin or other salicylates (Case 1). The latency to onset ranges from 1 to 4 weeks and the pattern of enzyme elevations is typically cholestatic, but can also be mixed. Most patients have immunoallergic manifestations such as rash, fever and arthralgiaseosinophilia or atypical lymphocytosis are also common. A history of aspirin allergy has not been reported among cases with allergic reactions to diflunisal. Diflunisal is not a commonly used drug and is not mentioned in large case series on drug induced liver injury or acute liver failure.
노출 경로	Rapidly and completely absorbed following oral administration, with a bioavailability of 80-90%. Peak plasma concentrations are achieved 2 - 3 hours following oral administration.

용도

개요

Diflunisal is more potent than aspirin but produces fewer side effects and has a biological half-life three to four times greater than that of aspirin. It is rapidly and completely absorbed on oral administration, with peak plasma levels being achieved within 2 to 3 hours of administration. It is highly bound (99%) to plasma proteins after absorption. Its elimination half-life is 8 to 12 hours, and it is excreted into urine primarily as glucuronide conjugates. The most frequently reported side effects include disturbances of the GI system (e.g., nausea, dyspepsia, and diarrhea), dermatological reactions, and CNS effects (e.g., dizziness and headache).

용도

As a prostaglandin synthetase inhibitor, diflunisal exhibits analgesic, fever-reducing, and anti-inflammatory action. It is used for long- and short-lasting symptomatic relief of low to moderate pain in osteoarthritis and rheumatoid arthritis.

일반 설명

Diflunisal (Dolobid), is a longer acting and more potent drugthan aspirin because of its hydrophobic, 2,4-difluorophenylgroup attached to the 5-position of the salicyclic acid. In alarge-scale comparative study with aspirin, it was also bettertolerated with less GI complications than aspirin. It ismarketed in tablet form for treating mild to moderate postoperativepain as well as RA and OA.Diflunisal is highly protein bound. Its metabolism is subjectto a dose-dependent, saturable, and capacity-limitedglucuronide formation. This unusual pharmacokineticprofile is a result of an enterohepatic circulation and the reabsorptionof 65% of the drug and its glucuronides, followedby cleavage of its unstable, acyl glucuronide back tothe active drug. Thus, diflunisal usage in patients with renalimpairment should be closely monitored.