Synthesis of low-cost inhibitors of Spleen Tyrosine Kinase (SyK) for veterinary applications

Resumen

Spleen tyrosine kinase (Syk) is a cytosolic enzyme that couples immune cell receptors to intracellular signaling, regulating inflammatory responses and supporting neoplastic cell survival. This study reports the synthesis of low-molecular-weight compounds with potential Syk inhibitory activity, designed as cost-effective candidates for veterinary applications.

Objective: To design, synthesize, and chemically characterize low-molecular-weight Syk inhibitors as potential anti-inflammatory and anticancer agents for veterinary use, employing a pharmacophore-based modeling strategy.

Design/Methodology/Approach: The synthetic strategy employed general pyrimidine modification protocols amenable to scale-up for pilot plant production. Blind docking simulations were conducted to estimate the interactions and binding affinities between the synthesized compounds and the Syk protein.

Results: Twenty trisubstituted pyrimidine derivatives were synthesized with yields ranging from 51% to 72%. These compounds incorporated diverse functional groups—aromatic, alkoxy, and nitrilomethylene—strategically introduced to enhance pharmacological potential while maintaining synthetic accessibility.

Limitations/Implications: This investigation was limited to laboratory-scale synthesis, chemical characterization, and blind docking analysis to estimate binding affinity. Further work is needed to optimize reaction conditions and purification protocols at the pilot-plant level to evaluate industrial scalability.

Findings/Conclusions: A total of 20 compounds bearing diverse substituents at the 2, 4, and 6 positions of the pyrimidine ring were synthesized and characterized. Notably, one compound exhibited 96% similarity in predicted binding affinity to the most potent known Syk inhibitor.