1435467-38-1

Basic information

• Product Name: PF-06281355
• Synonyms: PF-06281355;PF-1355;PF-06281355 (Free base);2-(6-(2,5-dimethoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide
• CAS NO: 1435467-38-1
• Molecular Formula: C₁₄H₁₅N₃O₄S
• Molecular Weight: 321.3516
• EINECS: -0
• Mol File: 1435467-38-1.mol

Chemical Properties

• Appearance: /
• Density: 1.43±0.1 g/cm3(Predicted)
• PKA: 6.93±0.40(Predicted)
• CAS DataBase Reference: PF-06281355(CAS DataBase Reference)
• NIST Chemistry Reference: PF-06281355(1435467-38-1)
• EPA Substance Registry System: PF-06281355(1435467-38-1)

Safety Data

• Hazardous Substances Data: 1435467-38-1(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
PF-06281355 is used as an immunomodulatory agent for its potential to treat inflammatory and autoimmune diseases. By inhibiting the TYK2 enzyme, it can help reduce disease activity and inflammation in conditions such as psoriasis, lupus, and inflammatory bowel disease.
Used in Clinical Research:
PF-06281355 is utilized as a subject of clinical trials to evaluate its efficacy and safety in managing the symptoms and progression of inflammatory and autoimmune diseases. The results from these trials are crucial for determining the therapeutic potential of PF-06281355 and guiding its further development as a treatment option.
Used in Drug Development:
PF-06281355 serves as a lead compound in the development of new pharmaceuticals targeting the JAK-STAT signaling pathway. Its unique mechanism of action and demonstrated effectiveness in clinical trials make it a valuable asset in the search for novel treatments for a range of immune-related disorders.

Upstream product

• 2785-98-0 2,5-dimethoxybenzoic acid 
• 1435472-77-7 sodium 1-(2,5-dimethoxyphenyl)-3-ethoxy-3-oxoprop-1-en-1-olate 
• 60946-75-0 ethyl 3-oxo-3-(2,5-dimethoxyphenyl)propionate 
• 2290-65-5 trimethylsilyl isothiocyanate 
• 1435472-78-8 ethyl (Z)-3-( (2-amino-2-oxoethyl)amino)-3-(2,5-dimethoxyphenyl)acrylate 

Relevant articles and documents

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

Myeloperoxidase (MPO) is a heme peroxidase that catalyzes the production of hypochlorous acid. Clinical evidence suggests a causal role for MPO in various autoimmune and inflammatory disorders including vasculitis and cardiovascular and Parkinson's diseases, implying that MPO inhibitors may represent a therapeutic treatment option. Herein, we present the design, synthesis, and preclinical evaluation of N1-substituted-6-arylthiouracils as potent and selective inhibitors of MPO. Inhibition proceeded in a time-dependent manner by a covalent, irreversible mechanism, which was dependent upon MPO catalysis, consistent with mechanism-based inactivation. N1-Substituted-6-arylthiouracils exhibited low partition ratios and high selectivity for MPO over thyroid peroxidase and cytochrome P450 isoforms. N1-Substituted-6-arylthiouracils also demonstrated inhibition of MPO activity in lipopolysaccharide-stimulated human whole blood. Robust inhibition of plasma MPO activity was demonstrated with the lead compound 2-(6-(5-chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999, 8) upon oral administration to lipopolysaccharide-treated cynomolgus monkeys. On the basis of its pharmacological and pharmacokinetic profile, PF-06282999 has been advanced to first-in-human pharmacokinetic and safety studies.

2-Thiopyrimidinones

Myeloperoxidase inhibitors, pharmaceutical compositions containing such inhibitors and the use of such inhibitors to treat, for example, cardiovascular conditions.