Page last updated: 2024-11-06

azimilide

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth

Description

azimilide: structure given in first source; RN given refers to dihydrochloride [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID9571004
CHEBI ID34545
SCHEMBL ID26354
SCHEMBL ID26355
MeSH IDM0228342

Synonyms (25)

Synonym
azimilide
ne-10064
2,4-imidazolidinedione, 1-(((5-(4-chlorophenyl)-2-furanyl)methylene)amino)-3-(4-(4-methyl-1-piperazinyl)butyl)-
149908-53-2
chebi:34545 ,
74qu6p2934 ,
AKOS015960510
azimilide [who-dd]
azimilide [inn]
1-((5-(p-chlorophenyl)furfurylidene)amino)-3-(4-(4-methyl-1-piperazinyl)butyl)hydantoin
azimilide [mi]
DB04957
SCHEMBL26354
SCHEMBL26355
CS-3489
HY-18600
AC-8809
1-({(e)-[5-(4-chlorophenyl)furan-2-yl]methylidene}amino)-3-[4-(4-methylpiperazin-1-yl)butyl]imidazolidine-2,4-dione
1294552-65-0
(e)-1-(((5-(4-chlorophenyl)furan-2-yl)methylene)amino)-3-(4-(4-methylpiperazin-1-yl)butyl)imidazolidine-2,4-dione ,
ZFA90853
ZFA88894
2,4-imidazolidinedione,1-[[[5-(4-chlorophenyl)-2-furanyl]methylene]amino]-3-[4-(4-methyl-1-piperazinyl)butyl]-
2,4-imidazolidinedione, 1-[[[5-(4-chlorophenyl)-2-furanyl]methylene]amino]-3-[4-(4-methyl-1-piperazinyl)butyl]-
AKOS040745133

Research Excerpts

Toxicity

Azimilide showed promise as a safe and effective drug in reducing all-cause shocks, unplanned hospitalizations, and ED visits in ICD patients. The incidence of adverse events was lower in the azimilide group.

ExcerptReferenceRelevance
" The incidence of adverse events was lower in the azimilide group."( Results of a curtailed randomized controlled trial, evaluating the efficacy and safety of azimilide in patients with implantable cardioverter-defibrillators: The SHIELD-2 trial.
Bharucha, DB; Dorian, P; Kowey, PR; Mahaffey, KW; Robinson, VM, 2017
)
0.46
" Despite this limitation, azimilide showed promise as a safe and effective drug in reducing all-cause shocks, unplanned hospitalizations, and ED visits in ICD patients."( Results of a curtailed randomized controlled trial, evaluating the efficacy and safety of azimilide in patients with implantable cardioverter-defibrillators: The SHIELD-2 trial.
Bharucha, DB; Dorian, P; Kowey, PR; Mahaffey, KW; Robinson, VM, 2017
)
0.46

Pharmacokinetics

ExcerptReferenceRelevance
" Body weight-adjusted Cmax did not differ between genders."( Effect of age and gender on azimilide pharmacokinetics after a single oral dose of azimilide dihydrochloride.
Agnew, J; Bao, J; Bryson, P; Comer, P; Corey, A; Griffith, S; Li, J, 1997
)
0.3
" Unconfounded pharmacodynamic estimates required inclusion of circadian QTc variation in the pharmacodynamic model."( Pharmacokinetics and pharmacodynamics following intravenous doses of azimilide dihydrochloride.
Agnew, J; Brum, J; Corey, A; Parekh, N; Valentine, S; Williams, M, 1999
)
0.3
"2 L/kg (23%), and terminal exponential half-life = 78."( Azimilide pharmacokinetics following intravenous and oral administration of a solution and capsule formulation.
Agnew, JR; Corey, AE; Nesbitt, JD; Powell, JH; Thompson, GA; Valentine, SN; Wagner, DL, 1999
)
0.3
"Pharmacokinetic (PK) and pharmacodynamic (PD) models for azimilide were developed and validated with sparse blood sampling and QTc interval data obtained during three clinical trials of azimilide for prevention of supraventricular arrhythmia recurrence."( A population pharmacokinetic-pharmacodynamic analysis and model validation of azimilide.
Agnew, JR; Grasela, TH; Ludwig, EA; Phillips, L; Thompson, GA, 2001
)
0.31
" The pharmacokinetic and pharmacodynamic changes observed upon coadministration were small and are not expected to be clinically important."( Influence of coadministration on the pharmacokinetics of azimilide dihydrochloride and digoxin.
Agnew, JR; Corey, AE; Moehrke, W; Parekh, N; Powell, JH; Thompson, GA; Toothaker, RD; Valentine, SN, 2005
)
0.33
" pharmacokinetic data on 670 drugs representing, to our knowledge, the largest publicly available set of human clinical pharmacokinetic data."( Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
Lombardo, F; Obach, RS; Waters, NJ, 2008
)
0.35

Bioavailability

ExcerptReferenceRelevance
"This study investigated the relative oral bioavailability of azimilide dihydrochloride following administration in the fed (high-fat meal) and fasted states."( Comparative oral bioavailability of azimilide dihydrochloride in the fed and fasted states.
Agnew, JR; Corey, AE; Nesbitt, JD; Powell, JH; Thompson, GA; Valentine, SN; Wagner, DL, 2000
)
0.31

Dosage Studied

Oral azimilide significantly increased the time to first symptomatic recurrence of atrial fibrillation/flutter. Blood concentrations are essentially unaffected by renal function. An a priori dosage regimen adjustment is not required in patients with renal impairment.

ExcerptRelevanceReference
" Rats dosed orally (100 mg/kg) were fully protected from VF."( Efficacy of the class III antiarrhythmic agent azimilide in rodent models of ventricular arrhythmia.
Brooks, RR; Carpenter, JF; Maynard, AE; Miller, KE, 1996
)
0.29
" Dosing adjustments based on either age or gender are not required."( Effect of age and gender on azimilide pharmacokinetics after a single oral dose of azimilide dihydrochloride.
Agnew, J; Bao, J; Bryson, P; Comer, P; Corey, A; Griffith, S; Li, J, 1997
)
0.3
" At a dosage of 125 mg once daily, azimilide significantly increased the time to first symptomatic recurrence of atrial fibrillation/flutter."( Azimilide.
Clemett, D; Markham, A, 2000
)
0.31
" Patients received oral azimilide (100 mg in SVA-1 and SVA-3, 35 or 75 mg in SVA-2, and 125 mg in SVA-4) or matching placebo twice daily for 3 days (loading period), followed by once-daily dosing (maintenance period)."( Antiarrhythmic effects of azimilide in paroxysmal supraventricular tachycardia: efficacy and dose-response.
Connolly, SJ; Marcello, SR; Page, RL; Pritchett, EL; Schnell, DJ; Wilkinson, WE, 2002
)
0.31
"Since azimilide blood concentrations are essentially unaffected by renal function, an a priori dosage regimen adjustment is not required in patients with renal impairment."( Effect of severe renal impairment on the pharmacokinetics of azimilide following single dose oral administration.
Agnew, JR; Corey, AE; Parekh, NJ; Powell, JH; Thompson, GA; Valentine, SN, 2002
)
0.31
" Based on these results, no a priori dosage adjustment is required in subjects with mild to moderate hepatic impairment."( Effect of mild and moderate hepatic impairment on azimilide pharmacokinetics following single dose oral administration.
Agnew, JR; Corey, AE; King, EC; Parekh, NJ; Powell, JH; Thompson, GA, 2004
)
0.32
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Drug Classes (1)

ClassDescription
imidazolidine-2,4-dioneAn imidazolidinone with oxo groups at position 2 and 4.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (3)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Potassium voltage-gated channel subfamily H member 2Cavia porcellus (domestic guinea pig)IC50 (µMol)0.18000.18000.18000.1800AID397235
Potassium voltage-gated channel subfamily KQT member 1Cavia porcellus (domestic guinea pig)IC50 (µMol)0.24000.03102.31826.2000AID397236
Potassium voltage-gated channel subfamily H member 2Homo sapiens (human)IC50 (µMol)0.90320.00091.901410.0000AID161281; AID240820; AID243151; AID408340; AID420668; AID51930; AID576612
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (22)

Processvia Protein(s)Taxonomy
regulation of heart rate by cardiac conductionPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of heart rate by hormonePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of membrane potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
positive regulation of DNA-templated transcriptionPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
potassium ion homeostasisPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
cardiac muscle contractionPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of membrane repolarizationPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of ventricular cardiac muscle cell membrane repolarizationPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
cellular response to xenobiotic stimulusPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
potassium ion transmembrane transportPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
ventricular cardiac muscle cell action potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
membrane repolarizationPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
membrane depolarization during action potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
membrane repolarization during action potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
membrane repolarization during cardiac muscle cell action potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of heart rate by cardiac conductionPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
potassium ion export across plasma membranePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
membrane repolarization during ventricular cardiac muscle cell action potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of potassium ion transmembrane transportPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
negative regulation of potassium ion transmembrane transportPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
positive regulation of potassium ion transmembrane transportPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
negative regulation of potassium ion export across plasma membranePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
potassium ion import across plasma membranePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (12)

Processvia Protein(s)Taxonomy
transcription cis-regulatory region bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
inward rectifier potassium channel activityPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
voltage-gated potassium channel activityPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
delayed rectifier potassium channel activityPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
protein bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
ubiquitin protein ligase bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
identical protein bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
protein homodimerization activityPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
C3HC4-type RING finger domain bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarizationPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
scaffold protein bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarizationPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (5)

Processvia Protein(s)Taxonomy
plasma membranePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
cell surfacePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
perinuclear region of cytoplasmPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
voltage-gated potassium channel complexPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
inward rectifier potassium channel complexPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
plasma membranePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (20)

Assay IDTitleYearJournalArticle
AID397240Cardioprotective effect in isolated langendorff ischemia-reperfused Sprague-Dawley rat heart assessed as reduction of heart rate at 1 uM after 20 mins by RR interval ECG signal2009Bioorganic & medicinal chemistry letters, Mar-01, Volume: 19, Issue:5
Molecular hybridization, synthesis, and biological evaluation of novel chroman I(Kr) and I(Ks) dual blockers.
AID540210Clearance in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID540209Volume of distribution at steady state in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID397391Cardioprotective effect in isolated langendorff ischemia-reperfused Sprague-Dawley rat heart assessed as duration of QTc intervals at 1 uM after 20 mins2009Bioorganic & medicinal chemistry letters, Mar-01, Volume: 19, Issue:5
Molecular hybridization, synthesis, and biological evaluation of novel chroman I(Kr) and I(Ks) dual blockers.
AID397235Inhibition of ERG in guinea pig ventricular myocytes assessed as blockade of rapid delayed rectifier potassium current by whole cell patch-clamp technique2009Bioorganic & medicinal chemistry letters, Mar-01, Volume: 19, Issue:5
Molecular hybridization, synthesis, and biological evaluation of novel chroman I(Kr) and I(Ks) dual blockers.
AID540213Half life in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID51930K+ channel blocking activity in Chinese hamster ovary cells expressing HERG Kv11.12002Journal of medicinal chemistry, Aug-29, Volume: 45, Issue:18
Toward a pharmacophore for drugs inducing the long QT syndrome: insights from a CoMFA study of HERG K(+) channel blockers.
AID397236Inhibition of KVLQT1/minK in guinea pig ventricular myocytes assessed as blockade of slow delayed rectifier potassium current by whole cell patch-clamp technique2009Bioorganic & medicinal chemistry letters, Mar-01, Volume: 19, Issue:5
Molecular hybridization, synthesis, and biological evaluation of novel chroman I(Kr) and I(Ks) dual blockers.
AID397237Antiarrhythmic activity in langendorff ischemia-reperfused Sprague-Dawley rat heart assessed as cardiac protection at 1 uM2009Bioorganic & medicinal chemistry letters, Mar-01, Volume: 19, Issue:5
Molecular hybridization, synthesis, and biological evaluation of novel chroman I(Kr) and I(Ks) dual blockers.
AID540211Fraction unbound in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID240820Inhibitory concentration against IKr potassium channel2004Bioorganic & medicinal chemistry letters, Sep-20, Volume: 14, Issue:18
The pharmacophore hypotheses of I(Kr) potassium channel blockers: novel class III antiarrhythmic agents.
AID540212Mean residence time in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID408340Inhibition of human ERG expressed in CHO cells by whole cell patch clamp technique2008Bioorganic & medicinal chemistry, Jun-01, Volume: 16, Issue:11
Support vector machines classification of hERG liabilities based on atom types.
AID243151Inhibitory concentration against potassium channel HERG2005Bioorganic & medicinal chemistry letters, Jun-02, Volume: 15, Issue:11
A discriminant model constructed by the support vector machine method for HERG potassium channel inhibitors.
AID420669Lipophilicity, log D at pH 7.02009European journal of medicinal chemistry, May, Volume: 44, Issue:5
GRIND-based 3D-QSAR and CoMFA to investigate topics dominated by hydrophobic interactions: the case of hERG K+ channel blockers.
AID420668Inhibition of human ERG in MCF7 cells2009European journal of medicinal chemistry, May, Volume: 44, Issue:5
GRIND-based 3D-QSAR and CoMFA to investigate topics dominated by hydrophobic interactions: the case of hERG K+ channel blockers.
AID576612Inhibition of human ERG2011European journal of medicinal chemistry, Feb, Volume: 46, Issue:2
Predicting hERG activities of compounds from their 3D structures: development and evaluation of a global descriptors based QSAR model.
AID397390Cardioprotective effect in isolated langendorff ischemia-reperfused Sprague-Dawley rat heart assessed as duration of QT intervals at 1 uM after 20 mins2009Bioorganic & medicinal chemistry letters, Mar-01, Volume: 19, Issue:5
Molecular hybridization, synthesis, and biological evaluation of novel chroman I(Kr) and I(Ks) dual blockers.
AID161281Inhibition of human Potassium channel HERG expressed in mammalian cells2003Bioorganic & medicinal chemistry letters, Aug-18, Volume: 13, Issue:16
Prediction of hERG potassium channel affinity by traditional and hologram qSAR methods.
AID227700Anticonvulsant activity2003Bioorganic & medicinal chemistry letters, Aug-18, Volume: 13, Issue:16
Topological virtual screening: a way to find new anticonvulsant drugs from chemical diversity.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (139)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's37 (26.62)18.2507
2000's95 (68.35)29.6817
2010's7 (5.04)24.3611
2020's0 (0.00)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials27 (19.15%)5.53%
Reviews26 (18.44%)6.00%
Case Studies2 (1.42%)4.05%
Observational0 (0.00%)0.25%
Other86 (60.99%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (8)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
Compassionate Use Study to Assess the Long Term Safety of 125 mg Per Day of Oral Azimilide Dihydrochloride in One Patient Following Termination of the SHIELD Open-label Study 2001060 [NCT00752596]Phase 21 participants (Actual)Interventional2005-09-30Completed
A Multi-center, Open-label, Follow-up Study to Assess the Long-term Safety of 125 mg Per Day of Oral Azimilide Dihydrochloride in Patients With an Implantable Cardioverter Defibrillator [NCT00751738]Phase 3330 participants (Actual)Interventional2002-10-31Completed
Efficacy and Safety of Azimilide for the Treatment of Patients With Atrial Fibrillation [NCT00035477]Phase 3446 participants (Actual)Interventional2000-09-30Completed
A Double-blind, Randomized, Parallel-group, Placebo-controlled, Multiple-dose Study to Assess the Effect of 125 mg/Day Orally Administered Azimilide Dihydrochloride on Renal Function and Hemodynamics in Healthy Volunteers [NCT00318838]Phase 121 participants (Actual)Interventional2006-04-30Completed
Efficacy and Safety of Azimilide in the Prophylactic Treatment of Patients [NCT00035464]Phase 3431 participants (Actual)Interventional2000-12-31Completed
Efficacy and Safety Evaluation of Azimilide or Sotalol vs Placebo for Treatment of Patients With Atrial Fibrillation. [NCT00035451]Phase 3658 participants (Actual)Interventional2001-02-28Completed
Efficacy and Safety Evaluation of Azimilide Dihydrochloride in Patients With Implantable Cardioverter Defibrillators [NCT00035490]Phase 3633 participants (Actual)Interventional2001-09-30Completed
Phase 3 Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study of the Effects of Once Daily Oral Doses of 75 mg Azimilide Dihydrochloride on the Incidence of Cardiovascular Hospitalizations/Emergency Department Visits or Cardiovascular Death in [NCT01464476]Phase 3240 participants (Actual)Interventional2011-11-30Terminated
[information is prepared from clinicaltrials.gov, extracted Sep-2024]