基本情報
- CAS
133099-04-4- 標準SMILES
NC(=O)C(c1ccccc1)(c1ccccc1)[C@@H]1CCN(CCc2ccc3c(c2)CCO3)C1- InChIKey
HXGBXQDTNZMWGS-RUZDIDTESA-N- 分子式
- C28H30N2O2
- 平均分子量
- 426.5 g/mol
- 単同位体質量
- 426.2307282
概要
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.
名称と識別子
- 優先名称
- Darifenacin
- IUPAC
- 2-[(3S)-1-[2-(2,3-dihydro-1-benzofuran-5-yl)ethyl]pyrrolidin-3-yl]-2,2-diphenylacetamide
- 現地名
- ダリフェナシン
- 英語名
- Darifenacin
- 分子式
- C28H30N2O2
- 分子量
- 426.55
名称と別名
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
名称をさらに表示
ダリフェナシン2-[(3S)-1-[2-(2,3-ジヒドロ-1-ベンゾフラン-5-イル)エチル]ピロリジン-3-イル]-2,2-ジフェニルアセトアミドジフェニル[(3S)-1-[2-(2,3-ジヒドロベンゾフラン-5-イル)エチル]ピロリジン-3-イル]アセトアミド(3S)-1-[2-[(2,3-ジヒドロベンゾフラン)-5-イル]エチル]-α,α-ジフェニル-3-ピロリジンアセトアミドCS-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
物性
構造計算による物性
- XLogP
- 4.6
- 極性表面積
- 55.6 Ų
- 水素結合供与体数
- 1
- 水素結合受容体数
- 3
- 回転可能結合数
- 7
- 重原子数
- 32
- 形式電荷
- 0
- 複雑度
- 607
実験および物理化学的性質
DrugsPharmaceuticals -> Listed in ZINC15
LogP4.5
Solubility2.98e-04 g/L
Endocrine DisruptorsPotential endocrine disrupting compound
Physical DescriptionSolid
物理化学的性質
- 比旋光度
- 25 D · 25D -20.6° (c = 1.0 in methylene chloride)
- 沸点
- 614.3 · 614.3±55.0 °C(Predicted)
- 比重(密度)
- 1.192 · 1.192±0.06 g/cm3(Predicted)
- 貯蔵温度
- 2 · 2-8°C
- 溶解性
- Soluble in DMSO
- 外見
- Powder
- 酸解離定数(Pka)
- pKa (25°): 9.2
- 色
- White to off-white
安全と法規制
安全情報は参考情報です。供給元の安全データシート（SDS）、適用法令、専門家による評価に代わるものではありません。
毒性情報
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
化学と産業
薬理情報
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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