Synonym
PF-06281355; PF 06281355; PF06281355; PF-1355; PF 1355; PF1355.
IUPAC/Chemical Name
2-(6-(2,5-Dimethoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide
InChi Key
LJBUZOGABRDGBR-UHFFFAOYSA-N
InChi Code
InChI=1S/C14H15N3O4S/c1-20-8-3-4-11(21-2)9(5-8)10-6-13(19)16-14(22)17(10)7-12(15)18/h3-6H,7H2,1-2H3,(H2,15,18)(H,16,19,22)
SMILES Code
O=C(N)CN(C(N1)=S)C(C2=CC(OC)=CC=C2OC)=CC1=O
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
PF-1355 is a selective 2-thiouracil mechanism-based MPO inhibitor.
In vivo activity:
This study reports a selective 2-thiouracil mechanism-based MPO inhibitor (PF-1355 [2-(6-(2,5-dimethoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide) and demonstrate that MPO is a critical mediator of vasculitis in mouse disease models. Oral administration of PF-1355 reduced plasma MPO activity, vascular edema, neutrophil recruitment, and elevated circulating cytokines. In a model of anti-glomerular basement membrane disease, formerly known as Goodpasture disease, albuminuria and chronic renal dysfunction were completely suppressed by PF-1355 treatment.
Reference: J Pharmacol Exp Ther. 2015 May;353(2):288-98. https://pubmed.ncbi.nlm.nih.gov/25698787/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMSO |
30.0 |
93.36 |
|
| Ethanol |
5.0 |
15.56 |
|
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
321.35
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
Zheng W, Warner R, Ruggeri R, Su C, Cortes C, Skoura A, Ward J, Ahn K, Kalgutkar A, Sun D, Maurer TS, Bonin PD, Okerberg C, Bobrowski W, Kawabe T, Zhang Y, Coskran T, Bell S, Kapoor B, Johnson K, Buckbinder L. PF-1355, a mechanism-based myeloperoxidase inhibitor, prevents immune complex vasculitis and anti-glomerular basement membrane glomerulonephritis. J Pharmacol Exp Ther. 2015 May;353(2):288-98. doi: 10.1124/jpet.114.221788. Epub 2015 Feb 19. PMID: 25698787.
In vivo protocol:
Zheng W, Warner R, Ruggeri R, Su C, Cortes C, Skoura A, Ward J, Ahn K, Kalgutkar A, Sun D, Maurer TS, Bonin PD, Okerberg C, Bobrowski W, Kawabe T, Zhang Y, Coskran T, Bell S, Kapoor B, Johnson K, Buckbinder L. PF-1355, a mechanism-based myeloperoxidase inhibitor, prevents immune complex vasculitis and anti-glomerular basement membrane glomerulonephritis. J Pharmacol Exp Ther. 2015 May;353(2):288-98. doi: 10.1124/jpet.114.221788. Epub 2015 Feb 19. PMID: 25698787.
Ruggeri, R. B., Buckbinder, L., Bagley, S. W., Carpino, P. A., Conn, E. L., Dowling, M. S., ... & Kalgutkar, A. S. (2015). Discovery of 2-(6-(5-chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3, 4-dihydropyrimidin-1 (2 h)-yl) acetamide (pf-06282999): a highly selective mechanism-based myeloperoxidase inhibitor for the treatment of cardiovascular diseases. Journal of medicinal chemistry, 58(21), 8513-8528.
Bachmann, F., Duthaler, U., Rudin, D., Krähenbühl, S., & Haschke, M. (2018). N-demethylation of N-methyl-4-aminoantipyrine, the main metabolite of metamizole. European Journal of Pharmaceutical Sciences, 120, 172-180.
