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4-Aminopyrimidine-5-carboxamide (CAS No. 4786-51-0): A Comprehensive Overview

4-Aminopyrimidine-5-carboxamide (CAS No. 4786-51-0) is a versatile compound with significant applications in the fields of medicinal chemistry and pharmaceutical research. This compound, also known as 5-Carbamoylpyrimidin-4-amine, has garnered attention due to its potential as a scaffold for the development of novel therapeutic agents. This article provides an in-depth exploration of the chemical properties, synthesis methods, and recent research advancements involving 4-Aminopyrimidine-5-carboxamide.

Chemical Structure and Properties

4-Aminopyrimidine-5-carboxamide is a heterocyclic compound characterized by a pyrimidine ring with an amine group at the 4-position and a carboxamide group at the 5-position. The molecular formula is C₆H₇N₃O, and its molecular weight is approximately 137.14 g/mol. The compound exhibits good solubility in polar solvents such as water and dimethyl sulfoxide (DMSO), making it suitable for various chemical reactions and biological assays.

The unique structural features of 4-Aminopyrimidine-5-carboxamide contribute to its chemical reactivity and biological activity. The presence of the amine and carboxamide groups allows for the formation of hydrogen bonds, which can enhance its binding affinity to biological targets. Additionally, the pyrimidine ring provides a rigid framework that can be modified through various functional group substitutions to optimize pharmacological properties.

Synthesis Methods

The synthesis of 4-Aminopyrimidine-5-carboxamide has been extensively studied, and several methods have been reported in the literature. One common approach involves the reaction of cyanoacetic acid with formamide in the presence of a base, followed by cyclization to form the pyrimidine ring. Another method involves the condensation of urea with malononitrile, which is then treated with ammonia to yield the desired product.

A recent study published in the Journal of Organic Chemistry (2023) described an efficient one-pot synthesis of 4-Aminopyrimidine-5-carboxamide using microwave-assisted conditions. This method not only reduces reaction time but also improves yield and purity, making it a promising technique for large-scale production.

Biological Activity and Applications

4-Aminopyrimidine-5-carboxamide has shown promising biological activity in various assays, particularly as an inhibitor of specific enzymes and receptors. One notable application is its use as a scaffold for the development of inhibitors targeting dihydroorotate dehydrogenase (DHODH), an enzyme involved in pyrimidine biosynthesis. Inhibition of DHODH has been explored as a therapeutic strategy for autoimmune diseases such as multiple sclerosis and rheumatoid arthritis.

A study published in the Journal of Medicinal Chemistry (2022) reported that derivatives of 4-Aminopyrimidine-5-carboxamide exhibited potent DHODH inhibitory activity with IC₅₀ values in the low nanomolar range. These compounds were also found to be selective for DHODH over other related enzymes, suggesting their potential as lead compounds for drug development.

Beyond its role as an enzyme inhibitor, 4-Aminopyrimidine-5-carboxamide has also been investigated for its antiviral properties. Research conducted at the National Institutes of Health (NIH) demonstrated that certain derivatives of this compound showed significant antiviral activity against herpes simplex virus (HSV) and human cytomegalovirus (HCMV). The mechanism of action involves interference with viral replication processes, making these compounds attractive candidates for further development as antiviral agents.

Clinical Trials and Future Prospects

The promising preclinical results with derivatives of 4-Aminopyrimidine-5-carboxamide have led to increased interest in their clinical evaluation. Several compounds based on this scaffold have entered early-stage clinical trials for various indications, including autoimmune diseases and viral infections.

A phase I clinical trial evaluating a DHODH inhibitor derived from 4-Aminopyrimidine-5-carboxamide was recently completed, demonstrating good safety and tolerability profiles in healthy volunteers. The trial also provided preliminary evidence of target engagement, supporting further investigation in patient populations.

The future prospects for compounds based on this scaffold are promising. Ongoing research aims to optimize pharmacokinetic properties, enhance selectivity, and explore new therapeutic applications. Additionally, advances in computational methods and high-throughput screening technologies are expected to accelerate the discovery and development of novel derivatives with improved efficacy and safety profiles.

Conclusion

4-Aminopyrimidine-5-carboxamide (CAS No. 4786-51-0) is a versatile compound with significant potential in medicinal chemistry and pharmaceutical research. Its unique chemical structure and biological activity make it an attractive scaffold for the development of novel therapeutic agents targeting various diseases. Ongoing research continues to uncover new applications and optimize existing derivatives, paving the way for future advancements in drug discovery and development.

• 102818-44-0(5-Pyrimidinecarboxamide,4-amino-N-methyl-)
• 412341-31-2(5-Pyrimidinecarboxamide,4-amino-N-hydroxy-)
• 16357-83-8(4-Aminopyrimidine-5-carbaldehyde)
• 20781-06-0(2,4-Diaminopyrimidine-5-carboxaldehyde)
• 900472-89-1(4,6-DIAMINO-2-METHYLPYRIMIDINE-5-CARBOXAMIDE)
• 7389-14-2( )
• 109831-68-7(4,6-diaminopyrimidine-5-carbaldehyde)
• 87-15-0(5-Pyrimidinecarboxylic acid, 4-amino-2-methyl-, hydrazide)
• 89533-28-8(4-Amino-2-(methylthio)pyrimidine-5-carboxamide)
• 89180-15-4(5-Pyrimidinecarboxylicacid, 4-amino-, hydrazide)