| Identification | Back Directory | [Name]
PF-06282999 | [CAS]
1435467-37-0 | [Synonyms]
CS-2543
PF-06282999
PF-06282999 (Free base)
PF-06282999 >=98% (HPLC)
PF-06282999;PF 06282999;PF06282999
1(2H)-Pyrimidineacetamide, 6-(5-chloro-2-methoxyphenyl)-3,4-dihydro-4-oxo-2-thioxo-
2-(6-(5-chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide | [Molecular Formula]
C13H12ClN3O3S | [MDL Number]
MFCD30533689 | [MOL File]
1435467-37-0.mol | [Molecular Weight]
325.77 |
| Chemical Properties | Back Directory | [density ]
1.52±0.1 g/cm3(Predicted) | [storage temp. ]
room temp | [solubility ]
DMSO:30.0(Max Conc. mg/mL);92.1(Max Conc. mM) | [form ]
powder | [pka]
6.85±0.40(Predicted) | [color ]
white to beige |
| Hazard Information | Back Directory | [Biological Activity]
PF-06282999 is an orally active thiouracil class myeloperoxidase (MPO) suicide substrate (kinact/KI = 11600 M-1s-1) th at targets MPO heme group for mechanism-based irreversible inactivation wtih high selectivity over thyroid peroxidase (TPO kinact/KI <3 M-1s-1) and heme-containing cytochrome P450 (CYP) isoforms (IC50 >100 μM). PF-06282999 effectively inhibits MPO activity in human blood stimulated by LPS ex vivo (IC50 = 1.9 μM) and in blood of LPS-treated cynomolgus monkeys in vivo (5-80 mg/kg p.o. 1hr post LPS i.v.) with good pharmacokinetics and oral availability (100%/86%/75%/76% in mice/rats/dogs/monkeys). PF-06282999 also exhibits weak PXR activating activity (EC50/Emax = 279 μM/9.36-fold vs.0.8 μM/19.6-fold with rifampin). |
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