기본 정보
- CAS
133099-04-4- 표준 SMILES
NC(=O)C(c1ccccc1)(c1ccccc1)[C@@H]1CCN(CCc2ccc3c(c2)CCO3)C1- InChIKey
HXGBXQDTNZMWGS-RUZDIDTESA-N- 분자식
- C28H30N2O2
- 평균 분자량
- 426.5 g/mol
- 단동위원소 질량
- 426.2307282
개요
Darifenacin is 2-[(3S)-1-Ethylpyrrolidin-3-yl]-2,2-diphenylacetamide in which one of the hydrogens at the 2-position of the ethyl group is substituted by a 2,3-dihydro-1-benzofuran-5-yl group. It is a selective antagonist for the M3 muscarinic acetylcholine receptor, which is primarily responsible for bladder muscle contractions, and is used as the hydrobromide salt in the management of urinary incontinence. It has a role as a muscarinic antagonist and an antispasmodic drug. It is a monocarboxylic acid amide, a member of pyrrolidines and a member of 1-benzofurans.
이름 및 식별자
- 우선 이름
- Darifenacin
- IUPAC
- 2-[(3S)-1-[2-(2,3-dihydro-1-benzofuran-5-yl)ethyl]pyrrolidin-3-yl]-2,2-diphenylacetamide
- 현지명
- 다리페나신
- 영어명
- Darifenacin
- 분자식
- C28H30N2O2
- 분자량
- 426.55
이름 및 동의어
Darifenacin133099-04-42-[(3S)-1-[2-(2,3-dihydro-1-benzofuran-5-yl)ethyl]pyrrolidin-3-yl]-2,2-diphenylacetamideUK-88525darifenacineDarifenacinaDarifenacin extended releaseAPG9819VLMUK88525(S)-1-(2-(2,3-Dihydro-5-benzofuranyl)ethyl)-alpha,alpha-diphenyl-3-pyrrolidineacetamideDTXSID2048290CHEBI:391960
이름 더 보기
다리페나신CS-773UK 88525Darifenacin, >=98%Darifenacin USP/EP/BPTolafentrine Impurity 162-{(3S)-1-[2-(2,3-dihydro-1-benzofuran-5-yl)ethyl]pyrrolidin-3-yl}-2,2-dip2-{(3S)-1-[2-(2,3-dihydro-1-benzofuran-5-yl)ethyl]pyrrolidin-3-yl}-2,2-diphe
2-{(3S)-1-[2-(2,3-dihydro-1-benzofuran-5-yl)ethyl]pyrrolidin-3-yl}-2,2-diphenylacetamide3-Pyrrolidineacetamide, 1-(2-(2,3-dihydro-5-benzofuranyl)ethyl)-alpha,alpha-diphenyl-, (3S)-darifenicinDarifenacinum2-((3S)-1-(2-(2,3-dihydro-1-benzofuran-5-yl)ethyl)pyrrolidin-3-yl)-2,2-diphenylacetamide2-((3S)-1-(2-(2,3-dihydro-1-benzofuran-5-yl)ethyl)pyrrolidin-3-yl)-2,2-di(phenyl)acetamide2-[(3S)-1-[2-(2,3-dihydro-1-benzofuran-5-yl)ethyl]pyrrolidin-3-yl]-2,2-di(phenyl)acetamideRefChem:57150
물성
구조 계산 물성
- XLogP
- 4.6
- 극성 표면적
- 55.6 Ų
- 수소 결합 공여자 수
- 1
- 수소 결합 수용자 수
- 3
- 회전 가능 결합 수
- 7
- 무거운 원자 수
- 32
- 형식 전하
- 0
- 복잡도
- 607
실험 및 물리화학적 성질
DrugsPharmaceuticals -> Listed in ZINC15
LogP4.5
Solubility2.98e-04 g/L
Endocrine DisruptorsPotential endocrine disrupting compound
Physical DescriptionSolid
물리화학적 성질
- 끓는 점
- 614.3 · 614.3±55.0 °C(Predicted)
- 밀도
- 1.192 · 1.192±0.06 g/cm3(Predicted)
- 저장 조건
- 2 · 2-8°C
- 용해도
- DMSO에 용해됨
- 물리적 상태
- 가루
- 산도 계수 (pKa)
- pKa (25°): 9.2
- 색상
- White to off-white
안전 및 규제
안전 정보는 참고용이며, 공급업체의 물질안전보건자료(SDS), 관련 법규 및 전문가 평가를 대체하지 않습니다.
독성 정보
Hepatotoxicity
Like most anticholinergic agents, darifenacin has not been linked to liver enzyme elevations during therapy or to instances of clinically apparent liver injury with symptoms or jaundice. In multiple prospective clinical trial of darifenacin in patients with overactive bladder syndrome, ALT elevations were reported in less than 1% of treated subjects, rates similar to that of placebo recipients. Despite widespread clinical use for almost two decades, there have been no published case reports of clinically apparent liver injury convincingly attributed to darifenacin use.
Exposure RoutesThe mean oral bioavailability at steady state is estimated to be 15% and 19% for 7.5 mg and 15 mg tablets, respectively.
Toxicity SummaryDarifenacin selectively antagonizes the muscarinic M3 receptor. M3 receptors are involved in contraction of human bladder and gastrointestinal smooth muscle, saliva production, and iris sphincter function.
Signs and SymptomsOverdosage can potentially result in severe central anticholinergic effects.
Carcinogen ClassificationNo indication of carcinogenicity to humans (not listed by IARC).
Drug Induced Liver Injury
Drug-Induced Liver Injury Severity and Toxicity (DILIst)
darifenacin
DILI Negative
Oral
DOI:10.1016/j.drudis.2019.09.022
화학 및 산업
약리 정보
ATC Code
G04BD10
G - Genito urinary system and sex hormones
QG - Genito urinary system and sex hormones
Protein BindingDarifenacin is approximately 98% bound to plasma proteins (primarily to alpha-1-acid-glycoprotein).
Pharmacodynamics
Darifenacin is a competitive muscarinic receptor antagonist. <i>In vitro</i> studies using human recombinant muscarinic receptor subtypes show that darifenacin has greater affinity for the M3 receptor than for the other known muscarinic receptors (9 and 12-fold greater affinity for M3 compared to M1 and M5, respectively, and 59-fold greater affinity for M3 compared to both M2 and M4). Muscarinic receptors play an important role in several major cholinergically mediated functions, including contractions of the urinary bladder smooth muscle and stimulation of salivary secretion. Adverse drug effects such as dry mouth, constipation and abnormal vision may be mediated through effects on M3 receptors in these organs.
Mechanism of ActionDarifenacin selectively antagonizes the muscarinic M3 receptor. M3 receptors are involved in contraction of human bladder and gastrointestinal smooth muscle, saliva production, and iris sphincter function.
Biological Half-LifeThe elimination half-life of darifenacin following chronic dosing is approximately 13-19 hours.
Metabolism/Metabolites
Hepatic. Primarily mediated by the cytochrome P450 enzymes CYP2D6 and CYP3A4.
Hepatic. Primarily mediated by the cytochrome P450 enzymes CYP2D6 and CYP3A4. Half Life: The elimination half-life of darifenacin following chronic dosing is approximately 13-19 hours.
FDA Pharmacological Classification
APG9819VLM
DARIFENACIN
Established Pharmacologic Class [EPC] - Cholinergic Muscarinic Antagonist
Mechanisms of Action [MoA] - Cholinergic Muscarinic Antagonists
Darifenacin is a Cholinergic Muscarinic Antagonist. The mechanism of action of darifenacin is as a Cholinergic Muscarinic Antagonist.
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6건
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