Three novel families of A2B adenosine receptor antagonists were identified in the context of the structural exploration of the 3,4-dihydropyrimidin-2(1H)-one chemotype. The most appealing series contain imidazole, 1,2,4-triazole, or benzimidazole rings fused to the 2,3-positions of the parent diazinone core. The optimization process enabled identification of a highly potent (3.49 nM) A2B ligand that exhibits complete selectivity toward A1, A2A, and A3 receptors. The results of functional cAMP experiments confirmed the antagonistic behavior of representative ligands. The main SAR trends identified within the series were substantiated by a molecular modeling study based on a receptor-driven docking model constructed on the basis of the crystal structure of the human A2A receptor.

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Two 3D-hybrid monolithic catalysts containing immobilized copper and palladium species on a silica support were synthesized by 3D printing and a subsequent surface functionalization protocol. The resulting 3D monoliths provided a structure with pore sizes around 300 μm, high mechanical strength, and easy catalyst recyclability. The devices were designed to perform heterogeneous multicatalytic multicomponent reactions (MMCRs) based on a copper alkyne–azide cycloaddition (CuAAC) + palladium catalyzed cross-coupling (PCCC) strategy, which allowed the rapid assembly of variously substituted 1,2,3-triazoles using a mixture of tBuOH/H2O as solvent. The reusable multicatalytic system developed in this work is an example of a practical miniaturized and compartmental heterogeneous 3D-printed metal catalyst to perform MMCRs for solution chemistry.