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Details

Stereochemistry ACHIRAL
Molecular Formula C20H21N3O
Molecular Weight 319.4002
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of IMIDAFENACIN

SMILES

CC1=NC=CN1CCC(C(N)=O)(C2=CC=CC=C2)C3=CC=CC=C3

InChI

InChIKey=SQKXYSGRELMAAU-UHFFFAOYSA-N
InChI=1S/C20H21N3O/c1-16-22-13-15-23(16)14-12-20(19(21)24,17-8-4-2-5-9-17)18-10-6-3-7-11-18/h2-11,13,15H,12,14H2,1H3,(H2,21,24)

HIDE SMILES / InChI
Molecular Formula C20H21N3O
Molecular Weight 319.4002
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: Description was created based on several sources, including http://www.ncbi.nlm.nih.gov/pubmed/25636812

Imidafenacin (KRP-197/ONO-8025) is the latest antimuscarinic (AM) developed for the treatment of overactive bladder syndrome (OAB) and, at the moment, it is marketed only in Japan. It has high affinities for the M3 and M1 muscarinic receptor subtypes, a low affinity for M2 receptors, and a potent inhibitory activity against rhythmic bladder contractions. Imidafenacin has excellent efficacy, tolerability, and safety. It is indicated for patients with nocturia, nocturnal polyuria, and benign prostatic hyperplasia.

CNS Activity

CNS Penetrant
2554
Curator's Comment: Imidafenacin showed little binding to brain muscarinic receptors.

Originator

Approval Year

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
 6.8 nM [IC50]
Antagonist
2778
 7.55 nM [Ki]
Antagonist
2778
 1.42 nM [Ki]
Inhibitor
8297
 0.747 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8429
Uritos

Approved Use

For the treatment of Overactive bladder

Launch Date

2007
PubMed

PubMed

TitleDatePubMed
Synthesis and antimuscarinic activity of a series of 4-(1-Imidazolyl)-2,2-diphenylbutyramides: discovery of potent and subtype-selective antimuscarinic agents.
1999 Jun
Biomimetic oxidation of 2-methylimidazole derivative with a chemical model system for cytochrome P-450.
2002 Aug
Pharmacological effects of KRP-197 on the human isolated urinary bladder.
2003
Pharmacological effects of imidafenacin (KRP-197/ONO-8025), a new bladder selective anti-cholinergic agent, in rats. Comparison of effects on urinary bladder capacity and contraction, salivary secretion and performance in the Morris water maze task.
2007
Effects of imidafenacin (KRP-197/ONO-8025), a new anti-cholinergic agent, on muscarinic acetylcholine receptors. High affinities for M3 and M1 receptor subtypes and selectivity for urinary bladder over salivary gland.
2007
Drug-drug interactions in the metabolism of imidafenacin: role of the human cytochrome P450 enzymes and UDP-glucuronic acid transferases, and potential of imidafenacin to inhibit human cytochrome P450 enzymes.
2007 Feb
Synthesis of the metabolites of 4-(2-methyl-1H-imidazol-1-yl)-2,2-diphenylbutanamide (KRP-197/ONO-8025).
2007 Jul
Development and validation of bioanalytical methods for Imidafenacin (KRP-197/ONO-8025) and its metabolites in human plasma by liquid chromatography-tandem mass spectrometry.
2007 Jun 15
Absorption, metabolism, and excretion of [14C]imidafenacin, a new compound for treatment of overactive bladder, after oral administration to healthy male subjects.
2007 Sep
Development and validation of bioanalytical methods for imidafenacin (KRP-197/ONO-8025) and its metabolites in human urine by using liquid chromatography-tandem mass spectrometry.
2007 Sep
Population pharmacokinetic analysis of a novel muscarinic receptor antagonist, imidafenacin, in healthy volunteers and overactive bladder patients.
2008
No effect of imidafenacin, a novel antimuscarinic drug, on digoxin pharmacokinetics in healthy subjects.
2008
Absolute bioavailability of imidafenacin after oral administration to healthy subjects.
2008 Feb
Validation and application of a 96-well format solid-phase extraction and liquid chromatography-tandem mass spectrometry method for the quantitation of digoxin in human plasma.
2008 Jun 15
Effect of itraconazole on the pharmacokinetics of imidafenacin in healthy subjects.
2008 Mar
[Pharmacological and clinical profile of imidafenacin developed as a new therapeutic agent for overactive bladder].
2008 May
Long-term safety, tolerability, and efficacy of the novel anti-muscarinic agent imidafenacin in Japanese patients with overactive bladder.
2008 Oct
A randomized, double-blind, placebo-controlled phase II dose-finding study of the novel anti-muscarinic agent imidafenacin in Japanese patients with overactive bladder.
2008 Sep
Response to "Suspected differential interactions of digoxin with imidafenacin and propantheline; some thoughts for introspection".
2009
Suspected differential interactions of digoxin with imidafenacin and propantheline; some thoughts for introspection.
2009
Comparison of the effect of anti-muscarinic agents on bladder activity, urinary ATP level, and autonomic nervous system in rats.
2009 Apr
A randomized, double-blind, placebo- and propiverine-controlled trial of the novel antimuscarinic agent imidafenacin in Japanese patients with overactive bladder.
2009 May
The add-on effect of solifenacin for patients with remaining overactive bladder after treatment with tamsulosin for lower urinary tract symptoms suggestive of benign prostatic obstruction.
2010
Noninvasive evaluation of brain muscarinic receptor occupancy of oxybutynin, darifenacin and imidafenacin in rats by positron emission tomography.
2010 Jul 31
Application of a novel combination of near-infrared spectroscopy and a humidity-controlled 96-well plate to the characterization of the polymorphism of imidafenacin.
2010 Nov
Patents

Patents

07868183
1
JP2003201281A
1
JP2010013485A
1

Sample Use Guides

In Vivo Use Guide
Usually, for adults, a single dose of 0.1mg as imidafenacin is orally administered, twice daily, after each meal in the morning and evening. If the desired efficacy is not observed a single dose can be increased up to 0.2mg (0.4mg daily).
Route of Administration: Oral
In Vitro Use Guide
10(–8) to 10(–7) M Imidafenacin (KRP-197) significantly decreased electrical field stimulation-induced acetylcholine release and the contractile responses in a concentration-dependent manner.
Substance Class Chemical
Created
by admin
on Fri Dec 15 17:10:16 GMT 2023
Edited
by admin
on Fri Dec 15 17:10:16 GMT 2023
Record UNII
XJR8Y07LJO
Record Status Validated (UNII)
Record Version
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Name Type Language
IMIDAFENACIN
INN   JAN   MART.   WHO-DD  
INN  
Official Name English
URITOS
Brand Name English
STAYBLA
Brand Name English
IMIDAFENACIN [JAN]
Common Name English
KRP-197
Code English
IMIDAFENACIN [MART.]
Common Name English
ONO-8025
Code English
Imidafenacin [WHO-DD]
Common Name English
imidafenacin [INN]
Common Name English
IMIDAFENACIN [MI]
Common Name English
4-(2-METHYL-1H-IMIDAZOL-1-YL)-2,2-DIPHENYLBUTANAMIDE
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C29704
Created by admin on Fri Dec 15 17:10:16 GMT 2023 , Edited by admin on Fri Dec 15 17:10:16 GMT 2023
Code System Code Type Description
DRUG CENTRAL
4902
Created by admin on Fri Dec 15 17:10:16 GMT 2023 , Edited by admin on Fri Dec 15 17:10:16 GMT 2023
PRIMARY
MERCK INDEX
m11873
Created by admin on Fri Dec 15 17:10:16 GMT 2023 , Edited by admin on Fri Dec 15 17:10:16 GMT 2023
PRIMARY
MESH
C120953
Created by admin on Fri Dec 15 17:10:16 GMT 2023 , Edited by admin on Fri Dec 15 17:10:16 GMT 2023
PRIMARY
DRUG BANK
DB09262
Created by admin on Fri Dec 15 17:10:16 GMT 2023 , Edited by admin on Fri Dec 15 17:10:16 GMT 2023
PRIMARY
EPA CompTox
DTXSID00870104
Created by admin on Fri Dec 15 17:10:16 GMT 2023 , Edited by admin on Fri Dec 15 17:10:16 GMT 2023
PRIMARY
FDA UNII
XJR8Y07LJO
Created by admin on Fri Dec 15 17:10:16 GMT 2023 , Edited by admin on Fri Dec 15 17:10:16 GMT 2023
PRIMARY
NCI_THESAURUS
C83789
Created by admin on Fri Dec 15 17:10:16 GMT 2023 , Edited by admin on Fri Dec 15 17:10:16 GMT 2023
PRIMARY
PUBCHEM
6433090
Created by admin on Fri Dec 15 17:10:16 GMT 2023 , Edited by admin on Fri Dec 15 17:10:16 GMT 2023
PRIMARY
CAS
170105-16-5
Created by admin on Fri Dec 15 17:10:16 GMT 2023 , Edited by admin on Fri Dec 15 17:10:16 GMT 2023
PRIMARY
WIKIPEDIA
IMIDAFENACIN
Created by admin on Fri Dec 15 17:10:16 GMT 2023 , Edited by admin on Fri Dec 15 17:10:16 GMT 2023
PRIMARY
INN
8402
Created by admin on Fri Dec 15 17:10:16 GMT 2023 , Edited by admin on Fri Dec 15 17:10:16 GMT 2023
PRIMARY
SMS_ID
100000124434
Created by admin on Fri Dec 15 17:10:16 GMT 2023 , Edited by admin on Fri Dec 15 17:10:16 GMT 2023
PRIMARY
ChEMBL
CHEMBL53366
Created by admin on Fri Dec 15 17:10:16 GMT 2023 , Edited by admin on Fri Dec 15 17:10:16 GMT 2023
PRIMARY
EVMPD
SUB32180
Created by admin on Fri Dec 15 17:10:16 GMT 2023 , Edited by admin on Fri Dec 15 17:10:16 GMT 2023
PRIMARY
Related Record Type Details
MUSCARINIC ACETYLCHOLINE RECEPTOR M1
TARGET -> INHIBITOR
CYTOCHROME P450 3A4
METABOLIC ENZYME -> SUBSTRATE
Structure of IMIDAFENACIN
EXCRETED UNCHANGED
URINE
MUSCARINIC ACETYLCHOLINE RECEPTOR M3
TARGET -> INHIBITOR
URIDINE DIPHOSPHATE GLUCURONOSYLTRANSFERASE 1A4
METABOLIC ENZYME -> SUBSTRATE
Related Record Type Details
Structure of 4-(2-METHYL-4,5-DIOXOIMIDAZOLIDIN-1-YL)-2,2-DIPHENYLBUTANAMIDE
METABOLITE -> PARENT
2h plasma
PLASMA
Structure of 4-((ACETIMIDOYL)AMINO)-2,2-DIPHENYLBUTANAMIDE
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2h plasma
PLASMA
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Structure of 3,3-DIPHENYL-2-PYRROLIDINONE
METABOLITE -> PARENT
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Structure of 4-(2-METHYLIMIDAZOL-1-YL)-2,2-DIPHENYL-BUTANAMIDE N-OXIDE
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Structure of N-(3-CARBAMOYL-3-(4-HYDROXYPHENYL)-3-PHENYLPROPYL)OXAMIDE
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Structure of 2-((4-AMINO-4-OXO-3,3-DIPHENYLBUTYL)AMINO)-2-OXOACETIC ACID
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URINE
Structure of (2S,3S,4S,5R,6R)-6-(3-(4-AMINO-4-OXO-3,3-DIPHENYL-BUTYL)-2-METHYL-IMIDAZOL-1-YL)-3,4,5-TRIHYDROXY-TETRAHYDROPYRAN-2-CARBOXYLIC ACID
METABOLITE -> PARENT
2h plasma
PLASMA
Related Record Type Details
Structure of IMIDAFENACIN
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC
NIH
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