Discovery of Potent and Highly Selective A_2B Adenosine Receptor Antagonist Chemotypes

Three novel families of A_2B adenosine receptor antagonists were identified in the context of the structural exploration of the 3,4-dihydropyrimidin-2­(1<i>H</i>)-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) A_2B ligand that exhibits complete selectivity toward A₁, A_2A, 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 A_2A receptor

Three-Dimensional Printing in Catalysis: Combining 3D Heterogeneous Copper and Palladium Catalysts for Multicatalytic Multicomponent Reactions

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

Discovery of Potent and Highly Selective A_2B Adenosine Receptor Antagonist Chemotypes

Three novel families of A_2B adenosine receptor antagonists were identified in the context of the structural exploration of the 3,4-dihydropyrimidin-2­(1<i>H</i>)-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) A_2B ligand that exhibits complete selectivity toward A₁, A_2A, 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 A_2A receptor