1435467-37-0

Basic information

• Product Name: PF-06282999
• Synonyms: PF-06282999;PF-06282999 (Free base);2-(6-(5-chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide
• CAS NO: 1435467-37-0
• Molecular Formula: C₁₃H₁₂ClN₃O₃S
• Molecular Weight: 325.77068
• EINECS: -0
• Mol File: 1435467-37-0.mol

Chemical Properties

• Appearance: /
• Density: 1.52±0.1 g/cm3(Predicted)
• Storage Temp.: room temp
• PKA: 6.85±0.40(Predicted)
• CAS DataBase Reference: PF-06282999(CAS DataBase Reference)
• NIST Chemistry Reference: PF-06282999(1435467-37-0)
• EPA Substance Registry System: PF-06282999(1435467-37-0)

Safety Data

• Hazardous Substances Data: 1435467-37-0(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
PF-06282999 is used as a migraine treatment agent for its ability to effectively reduce the frequency and severity of migraine attacks. Its mechanism of action involves blocking the CGRP receptor, which is instrumental in the transmission of pain signals associated with migraines.
Used in Migraine Prevention:
PF-06282999 is used as a preventive measure for migraines, offering a potential oral treatment option. It is being investigated as an alternative to existing therapies, such as triptans and monoclonal antibodies that target the CGRP pathway, due to its demonstrated efficacy and favorable safety profile.

Upstream product

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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.