Compounds > pf-06282999
Page last updated: 2024-11-13

pf-06282999

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Description

2-(6-(5-chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide: a myeloperoxidase inhibitor for treatment of cardiovascular diseases; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID71571306
CHEMBL ID3633460
SCHEMBL ID14936135
MeSH IDM000614917

Synonyms (28)

Synonym
bdbm50133595
chembl3633460 ,
ICYNYWFGIDGBRD-UHFFFAOYSA-N ,
2-(6-(5-chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2h)-yl)acetamide
2-(6-(5-chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2h)-yl) acetamide
S6648
SCHEMBL14936135
pf-06282999
1(2h)-pyrimidineacetamide, 6-(5-chloro-2-methoxyphenyl)-3,4-dihydro-4-oxo-2-thioxo-
YO3O4Q2NC8 ,
unii-yo3o4q2nc8
1435467-37-0
HY-19321
CS-6095
gtpl10053
2-[6-(5-chloro-2-methoxyphenyl)-4-oxo-2-sulfanylidenepyrimidin-1-yl]acetamide
compound 8 [pmid: 26509551]
DB11683
AKOS032945085
BCP20203
EX-A2535
BS-15745
pf06282999
pf 06282999
Q27294622
D84053
AC-36118
A902781

Research Excerpts

Pharmacokinetics

ExcerptReferenceRelevance
" Human pharmacokinetic predictions using single-species scaling of dog and/or monkey pharmacokinetics were consistent with the parameters observed in the first-in-human study, conducted in healthy volunteers at a dose range of 20-200 mg PF-06282999."( Pharmacokinetics and Disposition of the Thiouracil Derivative PF-06282999, an Orally Bioavailable, Irreversible Inactivator of Myeloperoxidase Enzyme, Across Animals and Humans.
Di, L; Dong, JQ; Feng, B; Kalgutkar, AS; Ryder, T; Sagawa, K; Terra, SG; Varma, MV; Wolford, A, 2016)		0.86

Bioavailability

ExcerptReferenceRelevance
" Pharmacokinetics in preclinical species characterized by low to moderate plasma clearances, good oral bioavailability at 3- to 5-mg/kg doses, and renal clearance as the projected major clearance mechanism in humans."( Pharmacokinetics and Disposition of the Thiouracil Derivative PF-06282999, an Orally Bioavailable, Irreversible Inactivator of Myeloperoxidase Enzyme, Across Animals and Humans.
Di, L; Dong, JQ; Feng, B; Kalgutkar, AS; Ryder, T; Sagawa, K; Terra, SG; Varma, MV; Wolford, A, 2016)		0.67
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (2)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
MyeloperoxidaseHomo sapiens (human)IC50 (µMol)17.84350.02001.88117.6800AID1875005; AID1875007
MyeloperoxidaseHomo sapiens (human)Ki0.31620.00190.13600.3162AID1256933
Thyroid peroxidaseHomo sapiens (human)IC50 (µMol)0.99000.40001.69253.3800AID1875008
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (19)

Processvia Protein(s)Taxonomy
hydrogen peroxide catabolic processMyeloperoxidaseHomo sapiens (human)
response to yeastMyeloperoxidaseHomo sapiens (human)
hypochlorous acid biosynthetic processMyeloperoxidaseHomo sapiens (human)
respiratory burst involved in defense responseMyeloperoxidaseHomo sapiens (human)
defense responseMyeloperoxidaseHomo sapiens (human)
response to oxidative stressMyeloperoxidaseHomo sapiens (human)
response to mechanical stimulusMyeloperoxidaseHomo sapiens (human)
removal of superoxide radicalsMyeloperoxidaseHomo sapiens (human)
response to foodMyeloperoxidaseHomo sapiens (human)
response to lipopolysaccharideMyeloperoxidaseHomo sapiens (human)
low-density lipoprotein particle remodelingMyeloperoxidaseHomo sapiens (human)
hydrogen peroxide catabolic processMyeloperoxidaseHomo sapiens (human)
negative regulation of apoptotic processMyeloperoxidaseHomo sapiens (human)
defense response to fungusMyeloperoxidaseHomo sapiens (human)
response to gold nanoparticleMyeloperoxidaseHomo sapiens (human)
defense response to bacteriumMyeloperoxidaseHomo sapiens (human)
thyroid hormone generationThyroid peroxidaseHomo sapiens (human)
response to oxidative stressThyroid peroxidaseHomo sapiens (human)
embryonic hemopoiesisThyroid peroxidaseHomo sapiens (human)
hormone biosynthetic processThyroid peroxidaseHomo sapiens (human)
hydrogen peroxide catabolic processThyroid peroxidaseHomo sapiens (human)
cellular oxidant detoxificationThyroid peroxidaseHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (8)

Processvia Protein(s)Taxonomy
chromatin bindingMyeloperoxidaseHomo sapiens (human)
peroxidase activityMyeloperoxidaseHomo sapiens (human)
protein bindingMyeloperoxidaseHomo sapiens (human)
heparin bindingMyeloperoxidaseHomo sapiens (human)
heme bindingMyeloperoxidaseHomo sapiens (human)
metal ion bindingMyeloperoxidaseHomo sapiens (human)
iodide peroxidase activityThyroid peroxidaseHomo sapiens (human)
peroxidase activityThyroid peroxidaseHomo sapiens (human)
calcium ion bindingThyroid peroxidaseHomo sapiens (human)
heme bindingThyroid peroxidaseHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (13)

Processvia Protein(s)Taxonomy
extracellular regionMyeloperoxidaseHomo sapiens (human)
extracellular spaceMyeloperoxidaseHomo sapiens (human)
nucleusMyeloperoxidaseHomo sapiens (human)
nucleoplasmMyeloperoxidaseHomo sapiens (human)
lysosomeMyeloperoxidaseHomo sapiens (human)
secretory granuleMyeloperoxidaseHomo sapiens (human)
azurophil granule lumenMyeloperoxidaseHomo sapiens (human)
azurophil granuleMyeloperoxidaseHomo sapiens (human)
intracellular membrane-bounded organelleMyeloperoxidaseHomo sapiens (human)
extracellular exosomeMyeloperoxidaseHomo sapiens (human)
phagocytic vesicle lumenMyeloperoxidaseHomo sapiens (human)
extracellular spaceMyeloperoxidaseHomo sapiens (human)
extracellular spaceThyroid peroxidaseHomo sapiens (human)
plasma membraneThyroid peroxidaseHomo sapiens (human)
cell surfaceThyroid peroxidaseHomo sapiens (human)
extracellular spaceThyroid peroxidaseHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (62)

Assay IDTitleYearJournalArticle
AID1256996Mutagenicity in Salmonella typhi by Ames test2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256932Lipophilicity, log D of the compound at pH 7.4 by shake-flask method2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256961Elimination half life in Beagle dog at 1 mg/kg, iv and 3 or 5 mg/kg, po2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1875005Inhibition of MPO (unknown origin) measured after 15 mins in presence of H2O2 by chemiluminescence assay2022Journal of medicinal chemistry, 09-08, Volume: 65, Issue:17
Discovery of AZD4831, a Mechanism-Based Irreversible Inhibitor of Myeloperoxidase, As a Potential Treatment for Heart Failure with Preserved Ejection Fraction.
AID1256979Reversible inhibition of CYP2C9 in human liver microsomes by LC-MS/MS analysis2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256963Elimination half life in cynomolgus monkey at 1 mg/kg, iv and 3 or 5 mg/kg, po2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256970Oral bioavailability in CD-1 mouse at 3 or 5 mg/kg2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1875007Inhibition of MPO in human HL-60 cells measured after 15 mins in presence of H2O2 by chemiluminescence assay2022Journal of medicinal chemistry, 09-08, Volume: 65, Issue:17
Discovery of AZD4831, a Mechanism-Based Irreversible Inhibitor of Myeloperoxidase, As a Potential Treatment for Heart Failure with Preserved Ejection Fraction.
AID1256953Plasma clearance in Beagle dog at 1 mg/kg, iv and 3 or 5 mg/kg, po2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256977Reversible inhibition of CYP2B6 bupropion hydroxylase activity in human liver microsomes by LC-MS/MS analysis2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256962Elimination half life in CD-1 mouse at 1 mg/kg, iv and 3 or 5 mg/kg, po2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256986Time-dependent inhibition of CYP2C9 in human liver microsomes2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256974Fraction unbound in dog plasma at 2 uM by equilibrium dialysis method2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256966Tmax in CD-1 mouse at 3 or 5 mg/kg, po2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256971Oral bioavailability in cynomolgus monkey at 3 or 5 mg/kg2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1875010Irreversible inhibition of MPO (unknown origin) assessed as fold shift in EC50 incubated with compound followed by drug washing and later treated with H2O2 for enzyme reactivation by chemiluminescence assay2022Journal of medicinal chemistry, 09-08, Volume: 65, Issue:17
Discovery of AZD4831, a Mechanism-Based Irreversible Inhibitor of Myeloperoxidase, As a Potential Treatment for Heart Failure with Preserved Ejection Fraction.
AID1256990Fraction unbound in human plasma at 2 uM by equilibrium dialysis method2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256984Time-dependent inhibition of CYP2B6 in human liver microsomes2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256960Elimination half life in Wistar rat at 1 mg/kg, iv and 3 or 5 mg/kg, po2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256987Time-dependent inhibition of CYP2C19 in human liver microsomes2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256983Time-dependent inhibition of CYP1A2 in human liver microsomes2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256930Inhibition of TPO (unknown origin) using Amplex Red as substrate assessed as formation of resorufin by measuring ratio of Kinact to Ki measured every 20 secs by spectrophotometric analysis2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256945Apparent permeability across RRCK cells2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256956Volume of distribution at steady state in Wistar rat at 1 mg/kg, iv and 3 or 5 mg/kg, po2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1875009Selectivity ratio of IC50 for human recombinant TPO (1 to 839 residues) expressed in baculovirus-infected insect cells to IC50 for MPO in human HL-60 cells2022Journal of medicinal chemistry, 09-08, Volume: 65, Issue:17
Discovery of AZD4831, a Mechanism-Based Irreversible Inhibitor of Myeloperoxidase, As a Potential Treatment for Heart Failure with Preserved Ejection Fraction.
AID1256969Oral bioavailability in Beagle dog at 3 or 5 mg/kg2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256934Inhibition of peroxidase activity of MPO isolated from human polynuclear leukocytes using Amplex Red as substrate assessed as formation of resorufin by measuring ratio of Kinact to Ki measured every 20 secs by spectrophotometric analysis2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256948Drug metabolism in sodium phosphate buffer assessed as formation of GSH adduct at 10 uM after 60 mins by LC-MS/MS analysis in presence of human MPO/H2O2/Cl-/excess GSH2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256933Inhibition of peroxidase activity of MPO isolated from human polynuclear leukocytes using Amplex Red as substrate assessed as formation of resorufin measured every 20 secs by spectrophotometric analysis2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256957Volume of distribution at steady state in Beagle dog at 1 mg/kg, iv and 3 or 5 mg/kg, po2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256994Drug excretion in Beagle dog urine at 1 mg/kg, iv2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256965Tmax in Beagle dog at 3 or 5 mg/kg, po2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256972Fraction unbound in mouse plasma at 2 uM by equilibrium dialysis method2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256980Reversible inhibition of CYP2C19 (S)-Mephenytoin 4'-hydroxylase activity in human liver microsomes by LC-MS/MS analysis2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256975Fraction unbound in monkey plasma at 2 uM by equilibrium dialysis method2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256981Reversible inhibition of CYP2D6 dextromethorphan O-demethylase activity in human liver microsomes by LC-MS/MS analysis2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256997In vivo inhibition of MPO in LPS-stimulated po dosed cynomolgous monkey administered 1 hr post LPS challenge measured after 2 hrs2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256995Drug excretion in cynomolgus monkey urine at 1 mg/kg, iv2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256973Fraction unbound in rat plasma at 2 uM by equilibrium dialysis method2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256989Time-dependent inhibition of CYP3A4 in human liver microsomes2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256931Inhibition of peroxidase activity of MPO isolated from human polynuclear leukocytes using Amplex Red as substrate assessed as partition ratio preincubated for 15 mins with H2O2 followed by 300 fold dilution measured immediately post dilution by spectropho2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256950Intrinsic apparent clearance in human liver microsomes2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256952Plasma clearance in Wistar rat at 1 mg/kg, iv and 3 or 5 mg/kg, po2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256955Plasma clearance in cynomolgus monkey at 1 mg/kg, iv and 3 or 5 mg/kg, po2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256992Metabolic stability in cryopreserved human hepatocytes assessed as GSH adduct formation2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256982Reversible inhibition of CYP3A4 in human liver microsomes by LC-MS/MS analysis2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256958Volume of distribution at steady state in CD-1 mouse at 1 mg/kg, iv and 3 or 5 mg/kg, po2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256968Oral bioavailability in Wistar rat at 3 or 5 mg/kg2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256985Time-dependent inhibition of CYP2C8 in human liver microsomes2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256959Volume of distribution at steady state in cynomolgus monkey at 1 mg/kg, iv and 3 or 5 mg/kg, po2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256954Plasma clearance in CD-1 mouse at 1 mg/kg, iv and 3 or 5 mg/kg, po2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256935Irreversible inhibition of MPO in LPS-stimulated human whole blood after 4 hrs by Amplex Red/H2O2-based fluorescence plate reader analysis2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256951Intrinsic apparent clearance in human hepatocytes assessed per 10'6 cells2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256964Tmax in Wistar rat at 3 or 5 mg/kg, po2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256978Reversible inhibition of CYP2C8 amodiaquine-N-deethylase activity in human liver microsomes by LC-MS/MS analysis2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256993Drug excretion in Wistar rat urine at 1 mg/kg, iv2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1875008Inhibition of human recombinant TPO (1 to 839 residues) expressed in baculovirus-infected insect cells measured after 15 mins in presence of H2O2 by chemiluminescence assay2022Journal of medicinal chemistry, 09-08, Volume: 65, Issue:17
Discovery of AZD4831, a Mechanism-Based Irreversible Inhibitor of Myeloperoxidase, As a Potential Treatment for Heart Failure with Preserved Ejection Fraction.
AID1256976Reversible inhibition of CYP1A2 phenacetin O-deethylase activity in human liver microsomes by LC-MS/MS analysis2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256967Tmax in cynomolgus monkey at 3 or 5 mg/kg, po2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256988Time-dependent inhibition of CYP2D6 in human liver microsomes2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1256991Metabolic stability in NADPH-supplemented human liver microsomes assessed as GSH adduct formation2015Journal of medicinal chemistry, Nov-12, Volume: 58, Issue:21
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.
AID1347411qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: primary screen against the NCATS Mechanism Interrogation Plate v5.0 (MIPE) Libary2020ACS chemical biology, 07-17, Volume: 15, Issue:7
High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (6)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's0 (0.00)29.6817
2010's4 (66.67)24.3611
2020's2 (33.33)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 (%)
Trials0 (0.00%)5.53%
Reviews0 (0.00%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other6 (100.00%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]
SubstanceRelationship StrengthStudiesTrialsClassesRoles
propylthiouracil
Propylthiouracil: A thiourea antithyroid agent. Propythiouracil inhibits the synthesis of thyroxine and inhibits the peripheral conversion of throxine to tri-iodothyronine. It is used in the treatment of hyperthyroidism. (From Martindale, The Extra Pharmacopeoia, 30th ed, p534). 6-propyl-2-thiouracil : A pyrimidinethione consisting of uracil in which the 2-oxo group is substituted by a thio group and the hydrogen at position 6 is substituted by a propyl group.		2.1110pyrimidinethioneantidote to paracetamol poisoning;
antimetabolite;
antioxidant;
antithyroid drug;
carcinogenic agent;
EC 1.14.13.39 (nitric oxide synthase) inhibitor;
hormone antagonist
thiouracil
Thiouracil: Occurs in seeds of Brassica and Crucifera species. Thiouracil has been used as antithyroid, coronary vasodilator, and in congestive heart failure although its use has been largely supplanted by other drugs. It is known to cause blood dyscrasias and suspected of terato- and carcinogenesis.. thiouracil : A nucleobase analogue that is uracil in which the oxo group at C-2 is replaced by a thioxo group.		7.1310nucleobase analogue;
thiocarbonyl compound		antithyroid drug;
metabolite
mocetinostat
mocetinostat: undergoing phase II clinical trials for treatment of cancer. mocetinostat : A benzamide obtained by formal condensation of the carboxy group of 4-({[4-(pyridin-3-yl)pyrimidin-2-yl]amino}methyl)benzoic acid with one of the amino groups of benzene-1,2-diamine. It is an orally active and isotype-selective HDAC inhibitor which exhibits antitumour activity (IC50 = 0.15, 0.29, 1.66 and 0.59 muM for HDAC1, HDAC2, HDAC3 and HDAC11).		3.0640aminopyrimidine;
benzamides;
pyridines;
secondary amino compound;
secondary carboxamide;
substituted aniline		antineoplastic agent;
apoptosis inducer;
autophagy inducer;
cardioprotective agent;
EC 3.5.1.98 (histone deacetylase) inhibitor;
hepatotoxic agent
pyrimidinones
Pyrimidinones: Heterocyclic compounds known as 2-pyrimidones (or 2-hydroxypyrimidines) and 4-pyrimidones (or 4-hydroxypyrimidines) with the general formula C4H4N2O.		3.0640
ConditionIndicatedRelationship StrengthStudiesTrials
Cardiovascular Diseases
Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.		07.1110
Cardiac Failure
[description not available]		02.4110
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.		02.4110
Atherogenesis
[description not available]		02.2110
Atheroma
[description not available]		02.2110
Atherosclerosis
A thickening and loss of elasticity of the walls of ARTERIES that occurs with formation of ATHEROSCLEROTIC PLAQUES within the ARTERIAL INTIMA.		02.2110