Related applications of 3-AMINO-6-BROMOPYRAZINE-2-CARBONITRILE(cas: 17231-51-5)

Product Manager: Selina Zhang; Email: selina@coreychem.com

3-Amino-6-bromopyrazine-2-carbonitrile (CAS: 17231-51-5) is a functionalized heterocyclic building block featuring a pyrazine core substituted with amino, bromo, and nitrile groups. With the molecular formula C₅H₃BrN₄ and a molecular weight of 199.01, this compound is characterized by its three orthogonal reactive handles, enabling diverse and targeted chemical transformations. The bromo substituent allows for palladium-catalyzed cross-coupling reactions (such as Suzuki-Miyaura, Buchwald-Hartwig, and Sonogashira couplings), the amino group enables amidation, reductive amination, and diazotization chemistry, while the nitrile group can be hydrolyzed, reduced, or converted to tetrazoles. This compound is primarily employed as a versatile intermediate in medicinal chemistry, drug discovery, and chemical biology for the preparation of heterocyclic pharmaceuticals, kinase inhibitors, and bioactive small molecules. Its primary applications are outlined below:

1. Medicinal Chemistry & Drug Discovery
Synthesis of Kinase Inhibitors

3-Amino-6-bromopyrazine-2-carbonitrile is a key building block for the synthesis of kinase inhibitors targeting pathways involved in cancer, inflammatory diseases, and metabolic disorders. The pyrazine core is a privileged scaffold in kinase inhibitor design, and the defined substitution pattern enables the construction of inhibitor libraries with predictable vector geometry for structure-activity relationship (SAR) studies.

EGFR and Other Receptor Tyrosine Kinase Inhibitors

Researchers have utilized this compound in the synthesis of heterocyclic inhibitors targeting EGFR and other receptor tyrosine kinases. Its bromo and amino handles allow for the introduction of diverse pharmacophores through sequential functionalization, facilitating the optimization of potency, selectivity, and pharmacokinetic properties.

Hedgehog Signaling Pathway Inhibitors

The compound serves as an intermediate in the preparation of small-molecule inhibitors of the Hedgehog signaling pathway, which is implicated in various cancers. For instance, its derivatives have been explored as antagonists of Smoothened (SMO) for the treatment of medulloblastoma and basal cell carcinoma.

2. Antiviral & Antimicrobial Research
Antiviral Agent Development

Heterocyclic compounds derived from 3-amino-6-bromopyrazine-2-carbonitrile have been screened for activity against viruses including hepatitis C virus (HCV), HIV, and influenza. The pyrazine-based scaffolds enable the discovery of novel antiviral agents by providing hydrogen-bonding and π-stacking interactions with viral proteins.

Antibacterial and Antifungal Studies

Pyrazine derivatives bearing amino and nitrile functionalities have demonstrated antibacterial and antifungal activities. Researchers use this compound as a precursor for synthesizing and screening novel antimicrobial agents against drug-resistant pathogens.

3. Oncology Research
PI3K/Akt/mTOR Pathway Modulation

The compound is used in the synthesis of inhibitors targeting the PI3K/Akt/mTOR signaling axis, a critical pathway frequently dysregulated in human cancers. Pyrazine-containing inhibitors have been optimized for improved potency, water solubility, and oral bioavailability.

DNA Repair Enzyme Inhibitors

Derivatives of 3-amino-6-bromopyrazine-2-carbonitrile have been investigated as inhibitors of DNA repair enzymes, including PARP (poly ADP-ribose polymerase), supporting research into synthetic lethality approaches for cancer therapy.

4. Chemical Biology & Probe Development
Chemical Probe Synthesis

The compound is employed as a core scaffold for the synthesis of chemical probes for target validation studies. Its multiple functional groups enable the incorporation of affinity tags, fluorescent labels, or photocrosslinkers for studying protein-ligand interactions and cellular mechanisms.

Fragment-Based Drug Discovery (FBDD)

With its relatively low molecular weight and three distinct binding motifs, this pyrazine compound serves as a versatile fragment for fragment-based drug discovery campaigns. Its bromine atom provides a convenient handle for crystallographic studies through anomalous scattering or heavy-atom derivatization.

5. Organic Synthesis & Heterocyclic Chemistry
Multi-Step Synthetic Route Development

The orthogonal reactivity of the amino, bromo, and nitrile groups enables sequential functionalization, allowing researchers to build structural complexity in a controlled and convergent manner. This makes the compound a valuable precursor for the synthesis of fused heterocycles, including pyrazolopyrazines, imidazopyrazines, and quinolines.

Aminopyrazine Scaffold Library Generation

Researchers utilize this compound to generate focused libraries of aminopyrazine derivatives for SAR studies. Libraries can be quickly diversified by exploiting the bromo handle via Suzuki cross-coupling with an array of boronic acids or boronic esters.

6. Radiochemistry & Isotope Labeling
Radioactive Labeling for Bioimaging and Biodistribution Studies

The bromine substituent of 3-amino-6-bromopyrazine-2-carbonitrile serves as a key functional handle for radiohalogenation using isotopes such as 76Br, 77Br, or 80mBr, generating radiolabeled probes for in vivo imaging applications (including PET and SPECT) and for tracking biodistribution and pharmacokinetics during drug development.

Synthesis of PET Tracers

Researchers have utilized this compound to access fluorine-18 labeled analogs, developing tracers targeting kinases and other disease-relevant proteins. The 3-aminopyrazine-2-carbonitrile scaffold is used as a platform for designing PET ligands with suitable physicochemical properties for central nervous system (CNS) imaging.

7. Handling & Storage
Storage Conditions

Store in tightly sealed containers under dry, cool, and well-ventilated conditions. Protect from moisture, excessive heat, and direct sunlight. Avoid contamination with strong oxidizing agents, acids, and bases. Appropriate laboratory safety procedures should be followed during handling.

Intended Use

This product is intended strictly for laboratory research, medicinal chemistry, drug discovery, chemical biology, and scientific investigation. It is not intended for therapeutic, diagnostic, food, or household applications without appropriate regulatory approval. Standard laboratory safety practices and protective equipment should be used during handling.

Summary

The value of 3-Amino-6-bromopyrazine-2-carbonitrile (CAS: 17231-51-5) lies in its unique combination of three orthogonal reactive handles, privileged pyrazine core, and defined substitution pattern. Its role as a key building block for kinase inhibitors, anticancer agents, antiviral compounds, chemical probes, and heterocyclic drug candidates makes it an indispensable tool for medicinal chemistry, drug discovery, and chemical biology research. The compound supports advanced investigations into kinase signaling pathways, cancer therapeutics, infectious disease research, and the development of next-generation pharmaceutical candidates across multiple disease areas.

For more information, please contact: selina@coreychem.com