PZ0375

PF-06282999

≥98% (HPLC)

• Synonym(s): 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide, 6-(5-Chloro-2-methoxyphenyl)-3,4-dihydro-4-oxo-2-thioxo-1(2H)-pyrimidineacetamide, PF 06282999, PF06282999
• Empirical Formula (Hill Notation): C₁₃H₁₂ClN₃O₃S
• CAS Number: 1435467-37-0
• Molecular Weight: 325.77
• MDL number: MFCD30533689
• UNSPSC Code: 51111800
• NACRES: NA.77

Properties

• Assay: ≥98% (HPLC)
• form: powder
• color: white to beige
• solubility: DMSO: 2 mg/mL, clear
• storage temp.: room temp
• SMILES string: O=C(N)CN(C(N1)=S)C(C2=CC(Cl)=CC=C2OC)=CC1=O
• InChI: 1S/C13H12ClN3O3S/c1-20-10-3-2-7(14)4-8(10)9-5-12(19)16-13(21)17(9)6-11(15)18/h2-5H,6H2,1H3,(H2,15,18)(H,16,19,21)
• InChI key: ICYNYWFGIDGBRD-UHFFFAOYSA-N

Description

Biochem/physiol Actions

PF-06282999 is an orally active thiouracil class myeloperoxidase (MPO) suicide substrate (k_inact/K_I = 11600 M^-1s^-1) that targets MPO heme group for mechanism-based irreversible inactivation wtih high selectivity over thyroid peroxidase (TPO k_inact/K_I <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).

Safety Information

• Storage Class Code: 11 - Combustible Solids
• WGK: WGK 3
• Flash Point(F): Not applicable
• Flash Point(C): Not applicable