Compounds > n-(4-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenyl)acetamide
Page last updated: 2024-11-12

n-(4-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenyl)acetamide

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

Description

N-(4-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenyl)acetamide: a metabolite of levosimendan; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID10131079
CHEMBL ID47975
SCHEMBL ID3723998
MeSH IDM0371010

Synonyms (12)

Synonym
n-[4-(4-methyl-6-oxo-4,5-dihydro-1h-pyridazin-3-yl)phenyl]acetamide
sk&f-93741
sk-93741
CHEMBL47975
FT-0661145
BRD-A69127847-001-01-1
SCHEMBL3723998
6-(4-acetylaminophenyl)-5-methyl-4,5-dihydro-3(2h)-pyridazinone
n-[4-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl]acetamide
DTXSID101154920
36725-27-6
n-(4-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenyl)acetamide

Research Excerpts

Pharmacokinetics

ExcerptReferenceRelevance
"The purpose of this study was to investigate the pharmacokinetics of levosimendan and to determine the primary pharmacokinetic parameters of the pharmacologically active metabolite OR-1896 in rapid and slow acetylators."( Pharmacokinetics of levosimendan and its active metabolite OR-1896 in rapid and slow acetylators.
Antila, S; Lehtonen, L; Nikkanen, H; Pesonen, U; Scheinin, H; Tapanainen, P; Vaahtera, K, 2004)		0.32
" In addition, pharmacokinetic parameters of total radiocarbon and the deacetylated congener, OR-1855, were determined."( Pharmacokinetics and excretion balance of OR-1896, a pharmacologically active metabolite of levosimendan, in healthy men.
Häkkinen, S; Koskinen, M; Laine, T; Pentikäinen, P; Pradhan, R; Puttonen, J; Ramela, M; Zhang, W, 2007)		0.34
" The pharmacokinetic parameters were calculated by three-compartmental methods."( Pharmacokinetics and excretion balance of OR-1896, a pharmacologically active metabolite of levosimendan, in healthy men.
Häkkinen, S; Koskinen, M; Laine, T; Pentikäinen, P; Pradhan, R; Puttonen, J; Ramela, M; Zhang, W, 2007)		0.34
" Mean terminal elimination half-life of OR-1896 (t(1/2)) was 70."( Pharmacokinetics and excretion balance of OR-1896, a pharmacologically active metabolite of levosimendan, in healthy men.
Häkkinen, S; Koskinen, M; Laine, T; Pentikäinen, P; Pradhan, R; Puttonen, J; Ramela, M; Zhang, W, 2007)		0.34
" The aim of this exploratory study was to assess the hemodynamic and pharmacokinetic interactions between digoxin and oral levosimendan as well as the proarrhythmic potential of this combination in patients with chronic heart failure."( The hemodynamic and pharmacokinetic interactions between chronic use of oral levosimendan and digoxin in patients with NYHA Classes II-III heart failure.
Harjola, VP; Jurkko, R; Nieminen, MS; Oikarinen, L; Puttonen, J; Sarapohja, T; Sundberg, S; Toivonen, L, 2008)		0.35
" Pharmacokinetic variables of levosimendan and digoxin were calculated in both treatment periods."( The hemodynamic and pharmacokinetic interactions between chronic use of oral levosimendan and digoxin in patients with NYHA Classes II-III heart failure.
Harjola, VP; Jurkko, R; Nieminen, MS; Oikarinen, L; Puttonen, J; Sarapohja, T; Sundberg, S; Toivonen, L, 2008)		0.35
" In contrast to the earlier data with intravenous levosimendan, the results indicate a pharmacokinetic interaction between levosimendan and digoxin."( The hemodynamic and pharmacokinetic interactions between chronic use of oral levosimendan and digoxin in patients with NYHA Classes II-III heart failure.
Harjola, VP; Jurkko, R; Nieminen, MS; Oikarinen, L; Puttonen, J; Sarapohja, T; Sundberg, S; Toivonen, L, 2008)		0.35
" In light of LVSMD pharmacological characteristics, we hypothesized that ECMO may induce major pharmacokinetic (PK) modifications for LVSMD and its metabolites."( Population Pharmacokinetics of Levosimendan and its Metabolites in Critically Ill Neonates and Children Supported or Not by Extracorporeal Membrane Oxygenation.
Berthomieu, L; Bourgoin, P; Chenouard, A; Davril, E; Duflot, T; Joram, N; Lamoureux, F; Lecomte, J; Oualha, M; Pereira, T, 2023)		0.91

Dosage Studied

ExcerptRelevanceReference
" Simulated data revealed that standard dosing may not be appropriate for patients under ECMO, with a decrease in the steady-state concentration of LVSMD and lower exposure to the active metabolite OR-1896."( Population Pharmacokinetics of Levosimendan and its Metabolites in Critically Ill Neonates and Children Supported or Not by Extracorporeal Membrane Oxygenation.
Berthomieu, L; Bourgoin, P; Chenouard, A; Davril, E; Duflot, T; Joram, N; Lamoureux, F; Lecomte, J; Oualha, M; Pereira, T, 2023)		0.91
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Bioassays (14)

Assay IDTitleYearJournalArticle
AID467618Vasodilatory activity in Wistar rat thoracic aortic ring assessed as inhibition of phenylephrine-induced contraction at 10 uM treated after phenylephrine challenge2009European journal of medicinal chemistry, Nov, Volume: 44, Issue:11
Synthesis and vasodilatory activity of some amide derivatives of 6-(4-carboxymethyloxyphenyl)-4,5-dihydro-3(2H)-pyridazinone.
AID176932Dose required to produce a 50% increase in blood flow to the autoperfused hindquarters of the anesthetized rat1988Journal of medicinal chemistry, Feb, Volume: 31, Issue:2
Design and synthesis of a series of combined vasodilator/beta-adrenoceptor antagonists based on 6-arylpyridazinones.
AID39457The dose required to cause 50% increase in the contractility and inotropic activity as dLVP/dt(max) in anesthetized cat1990Journal of medicinal chemistry, Jun, Volume: 33, Issue:6
1,4-bis(3-oxo-2,3-dihydropyridazin-6-yl)benzene analogues: potent phosphodiesterase inhibitors and inodilators.
AID59542Evaluated for percent increase in heart rate in anesthetized dogs1986Journal of medicinal chemistry, Oct, Volume: 29, Issue:10
Dihydropyridazinone cardiotonics: the discovery and inotropic activity of 1,3-dihydro-3,3-dimethyl-5-(1,4,5,6-tetrahydro-6-oxo-3-pyridazinyl)-2H -indol-2- one.
AID47756Compound was evaluated for inotropic activity in cat papillary muscles at concentration of (10e -4)M1986Journal of medicinal chemistry, Oct, Volume: 29, Issue:10
Dihydropyridazinone cardiotonics: the discovery and inotropic activity of 1,3-dihydro-3,3-dimethyl-5-(1,4,5,6-tetrahydro-6-oxo-3-pyridazinyl)-2H -indol-2- one.
AID47759Compound was evaluated for inotropic activity in cat papillary muscles at concentration of (10e-5) M1986Journal of medicinal chemistry, Oct, Volume: 29, Issue:10
Dihydropyridazinone cardiotonics: the discovery and inotropic activity of 1,3-dihydro-3,3-dimethyl-5-(1,4,5,6-tetrahydro-6-oxo-3-pyridazinyl)-2H -indol-2- one.
AID60457Compound was tested for cardiovascular profile in conscious dogs at dose of 500 ug/kg po1986Journal of medicinal chemistry, Oct, Volume: 29, Issue:10
Dihydropyridazinone cardiotonics: the discovery and inotropic activity of 1,3-dihydro-3,3-dimethyl-5-(1,4,5,6-tetrahydro-6-oxo-3-pyridazinyl)-2H -indol-2- one.
AID467619Vasodilatory activity in Wistar rat thoracic aortic ring assessed as inhibition of phenylephrine-induced contraction treated after phenylephrine challenge2009European journal of medicinal chemistry, Nov, Volume: 44, Issue:11
Synthesis and vasodilatory activity of some amide derivatives of 6-(4-carboxymethyloxyphenyl)-4,5-dihydro-3(2H)-pyridazinone.
AID60617Evaluated for percent decrease in maximum arterial blood pressure in anesthetized dogs1986Journal of medicinal chemistry, Oct, Volume: 29, Issue:10
Dihydropyridazinone cardiotonics: the discovery and inotropic activity of 1,3-dihydro-3,3-dimethyl-5-(1,4,5,6-tetrahydro-6-oxo-3-pyridazinyl)-2H -indol-2- one.
AID159191Inhibition of phosphodiesterase 3 enzyme activity by 50%1990Journal of medicinal chemistry, Jun, Volume: 33, Issue:6
1,4-bis(3-oxo-2,3-dihydropyridazin-6-yl)benzene analogues: potent phosphodiesterase inhibitors and inodilators.
AID39456ED15 is the dose producing 15% decrease in autoperfused hindquarters perfusion pressure in anesthetized cat1990Journal of medicinal chemistry, Jun, Volume: 33, Issue:6
1,4-bis(3-oxo-2,3-dihydropyridazin-6-yl)benzene analogues: potent phosphodiesterase inhibitors and inodilators.
AID177366Dose required to produce a fall in blood pressure of 40 mmHg in the anesthetized rat1988Journal of medicinal chemistry, Feb, Volume: 31, Issue:2
Design and synthesis of a series of combined vasodilator/beta-adrenoceptor antagonists based on 6-arylpyridazinones.
AID47760Compound was evaluated for inotropic activity in cat papillary muscles at concentration of (10e-6) M1986Journal of medicinal chemistry, Oct, Volume: 29, Issue:10
Dihydropyridazinone cardiotonics: the discovery and inotropic activity of 1,3-dihydro-3,3-dimethyl-5-(1,4,5,6-tetrahydro-6-oxo-3-pyridazinyl)-2H -indol-2- one.
AID59502Tested for cardiovascular contractility in anesthetized dogs1986Journal of medicinal chemistry, Oct, Volume: 29, Issue:10
Dihydropyridazinone cardiotonics: the discovery and inotropic activity of 1,3-dihydro-3,3-dimethyl-5-(1,4,5,6-tetrahydro-6-oxo-3-pyridazinyl)-2H -indol-2- one.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (24)

TimeframeStudies, This Drug (%)All Drugs %
pre-19902 (8.33)18.7374
1990's1 (4.17)18.2507
2000's15 (62.50)29.6817
2010's4 (16.67)24.3611
2020's2 (8.33)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 11.66

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be weak demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index11.66 (24.57)
Research Supply Index3.40 (2.92)
Research Growth Index5.06 (4.65)
Search Engine Demand Index0.00 (26.88)
Search Engine Supply Index0.00 (0.95)

This Compound (11.66)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials5 (20.83%)5.53%
Reviews0 (0.00%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other19 (79.17%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]
SubstanceRelationship StrengthStudiesTrialsClassesRoles
bupranolol
Bupranolol: An adrenergic-beta-2 antagonist that has been used for cardiac arrhythmia, angina pectoris, hypertension, glaucoma, and as an antithrombotic.		210aromatic ether
hydralazine
Hydralazine: A direct-acting vasodilator that is used as an antihypertensive agent.. hydralazine : The 1-hydrazino derivative of phthalazine; a direct-acting vasodilator that is used as an antihypertensive agent.		2.420azaarene;
hydrazines;
ortho-fused heteroarene;
phthalazines		antihypertensive agent;
vasodilator agent
isoproterenol
Isoproterenol: Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.. isoprenaline : A secondary amino compound that is noradrenaline in which one of the hydrogens attached to the nitrogen is replaced by an isopropyl group. A sympathomimetic acting almost exclusively on beta-adrenergic receptors, it is used (mainly as the hydrochloride salt) as a bronghodilator and heart stimulant for the management of a variety of cardiac disorders.		2.4120catechols;
secondary alcohol;
secondary amino compound		beta-adrenergic agonist;
bronchodilator agent;
cardiotonic drug;
sympathomimetic agent
milrinone
[no description available]		2.420bipyridines;
nitrile;
pyridone		cardiotonic drug;
EC 3.1.4.17 (3',5'-cyclic-nucleotide phosphodiesterase) inhibitor;
platelet aggregation inhibitor;
vasodilator agent
oxprenolol
Oxprenolol: A beta-adrenergic antagonist used in the treatment of hypertension, angina pectoris, arrhythmias, and anxiety.		1.9710aromatic ether
pindolol
Pindolol: A moderately lipophilic beta blocker (ADRENERGIC BETA-ANTAGONISTS). It is non-cardioselective and has intrinsic sympathomimetic actions, but little membrane-stabilizing activity. (From Martindale, The Extra Pharmocopoeia, 30th ed, p638). pindolol : A member of the class of indols which is the 2-hydroxy-3-(isopropylamino)propyl ether derivative of 1H-indol-4-ol.		1.9710indoles;
secondary amine		antiglaucoma drug;
antihypertensive agent;
beta-adrenergic antagonist;
serotonergic antagonist;
vasodilator agent
propranolol
Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for MYOCARDIAL INFARCTION; ARRHYTHMIA; ANGINA PECTORIS; HYPERTENSION; HYPERTHYROIDISM; MIGRAINE; PHEOCHROMOCYTOMA; and ANXIETY but adverse effects instigate replacement by newer drugs.. propranolol : A propanolamine that is propan-2-ol substituted by a propan-2-ylamino group at position 1 and a naphthalen-1-yloxy group at position 3.		1.9710naphthalenes;
propanolamine;
secondary amine		anti-arrhythmia drug;
antihypertensive agent;
anxiolytic drug;
beta-adrenergic antagonist;
environmental contaminant;
human blood serum metabolite;
vasodilator agent;
xenobiotic
valine
Valine: A branched-chain essential amino acid that has stimulant activity. It promotes muscle growth and tissue repair. It is a precursor in the penicillin biosynthetic pathway.. valine : A branched-chain amino acid that consists of glycine in which one of the hydrogens attached to the alpha-carbon is substituted by an isopropyl group.. L-valine : The L-enantiomer of valine.		2.0510L-alpha-amino acid zwitterion;
L-alpha-amino acid;
proteinogenic amino acid;
pyruvate family amino acid;
valine		algal metabolite;
Escherichia coli metabolite;
human metabolite;
micronutrient;
mouse metabolite;
nutraceutical;
Saccharomyces cerevisiae metabolite
dobutamine
Dobutamine: A catecholamine derivative with specificity for BETA-1 ADRENERGIC RECEPTORS. It is commonly used as a cardiotonic agent after CARDIAC SURGERY and during DOBUTAMINE STRESS ECHOCARDIOGRAPHY.. dobutamine : A catecholamine that is 4-(3-aminobutyl)phenol in which one of the hydrogens attached to the nitrogen is substituted by a 2-(3,4-dihydroxyphenyl)ethyl group. A beta1-adrenergic receptor agonist that has cardiac stimulant action without evoking vasoconstriction or tachycardia, it is used as the hydrochloride to increase the contractility of the heart in the management of acute heart failure.		2.0410catecholamine;
secondary amine		beta-adrenergic agonist;
cardiotonic drug;
sympathomimetic agent
imazodan
imazodan: RN & structure given in first source;		2.3720
valsartan
Valsartan: A tetrazole derivative and ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKER that is used to treat HYPERTENSION.. valsartan : A monocarboxylic acid amide consisting of L-valine in which the amino hydrogens have been replaced by a pentanoyl and a [2'-(1H-tetrazol-5-yl)biphenyl]-4-yl]methyl group. It exhibits antihypertensive activity.		2.0510biphenylyltetrazole;
monocarboxylic acid amide;
monocarboxylic acid		angiotensin receptor antagonist;
antihypertensive agent;
environmental contaminant;
xenobiotic
simendan
Simendan: A hydrazone and pyridazine derivative; the levo-form is a phosphodiesterase III inhibitor, calcium-sensitizing agent, and inotropic agent that is used in the treatment of HEART FAILURE.		6.89155
prizidilol
prizidilol: RN given refers to parent cpd; synonyms prizidilol & SK&F 92657 refer to di-HCl		1.9710
y 590
[no description available]		1.9610
emd 53998
EMD 53998: EMD 53998 is racemic; EMD 57439 is the (-)-isomer; EMD 57033 is the (+)-isomer		2.0210
digoxin
Digoxin: A cardiotonic glycoside obtained mainly from Digitalis lanata; it consists of three sugars and the aglycone DIGOXIGENIN. Digoxin has positive inotropic and negative chronotropic activity. It is used to control ventricular rate in ATRIAL FIBRILLATION and in the management of congestive heart failure with atrial fibrillation. Its use in congestive heart failure and sinus rhythm is less certain. The margin between toxic and therapeutic doses is small. (From Martindale, The Extra Pharmacopoeia, 30th ed, p666). digoxin : A cardenolide glycoside that is digitoxin beta-hydroxylated at C-12. A cardiac glycoside extracted from the foxglove plant, Digitalis lanata, it is used to control ventricular rate in atrial fibrillation and in the management of congestive heart failure with atrial fibrillation, but the margin between toxic and therapeutic doses is small.		3.4311cardenolide glycoside;
steroid saponin		anti-arrhythmia drug;
cardiotonic drug;
EC 3.6.3.9 (Na(+)/K(+)-transporting ATPase) inhibitor;
epitope
4,5-dihydro-6-(4-(imidazol-1-yl)phenyl)-5-methyl-3(2h)-pyridazinone
4,5-dihydro-6-(4-(imidazol-1-yl)phenyl)-5-methyl-3(2H)-pyridazinone: RN & structure given in first source		1.9710
indolidan
indolidan: structure given in first source		1.9610
ConditionIndicatedRelationship StrengthStudiesTrials
Blood Pressure, High
[description not available]		02.4520
Hypertension
Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.		02.4520
Critical Illness
A disease or state in which death is possible or imminent.		02.610
Auricular Fibrillation
[description not available]		02.610
Atrial Fibrillation
Abnormal cardiac rhythm that is characterized by rapid, uncoordinated firing of electrical impulses in the upper chambers of the heart (HEART ATRIA). In such case, blood cannot be effectively pumped into the lower chambers of the heart (HEART VENTRICLES). It is caused by abnormal impulse generation.		02.610
Chronic Illness
[description not available]		03.4311
Cardiac Failure
[description not available]		05.4453
Chronic Disease
Diseases which have one or more of the following characteristics: they are permanent, leave residual disability, are caused by nonreversible pathological alteration, require special training of the patient for rehabilitation, or may be expected to require a long period of supervision, observation, or care (Dictionary of Health Services Management, 2d ed). For epidemiological studies chronic disease often includes HEART DISEASES; STROKE; CANCER; and diabetes (DIABETES MELLITUS, TYPE 2).		03.4311
Heart Failure
A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION.		05.4453
Cardiac Remodeling, Ventricular
[description not available]		02.0510
Cardiac Hypertrophy
Enlargement of the HEART due to chamber HYPERTROPHY, an increase in wall thickness without an increase in the number of cells (MYOCYTES, CARDIAC). It is the result of increase in myocyte size, mitochondrial and myofibrillar mass, as well as changes in extracellular matrix.		02.0510
Albuminuria
The presence of albumin in the urine, an indicator of KIDNEY DISEASES.		02.0510
Cardiomegaly
Enlargement of the HEART, usually indicated by a cardiothoracic ratio above 0.50. Heart enlargement may involve the right, the left, or both HEART VENTRICLES or HEART ATRIA. Cardiomegaly is a nonspecific symptom seen in patients with chronic systolic heart failure (HEART FAILURE) or several forms of CARDIOMYOPATHIES.		02.0510
Diabetes Mellitus, Adult-Onset
[description not available]		02.0510
Cirrhosis
[description not available]		02.0510
Innate Inflammatory Response
[description not available]		02.0510
Cardiovascular Stroke
[description not available]		02.0510
Diabetes Mellitus, Type 2
A subclass of DIABETES MELLITUS that is not INSULIN-responsive or dependent (NIDDM). It is characterized initially by INSULIN RESISTANCE and HYPERINSULINEMIA; and eventually by GLUCOSE INTOLERANCE; HYPERGLYCEMIA; and overt diabetes. Type II diabetes mellitus is no longer considered a disease exclusively found in adults. Patients seldom develop KETOSIS but often exhibit OBESITY.		02.0510
Fibrosis
Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.		02.0510
Inflammation
A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.		02.0510
Myocardial Infarction
NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).		02.0510
Metabolic Acidosis
[description not available]		02.0110
Acidosis
A pathologic condition of acid accumulation or depletion of base in the body. The two main types are RESPIRATORY ACIDOSIS and metabolic acidosis, due to metabolic acid build up.		02.0110