9 research outputs found

    Integrated Ugi-Based Assembly of Functionally, Skeletally, and Stereochemically Diverse 1,4-Benzodiazepin-2-ones

    Get PDF
    A practical, integrated and versatile U-4CR-based assembly of 1,4-benzodiazepin-2-ones exhibiting functionally, skeletally, and stereochemically diverse substitution patterns is described. By virtue of its convergence, atom economy, and bond-forming efficiency, the methodology documented herein exemplifies the reconciliation of structural complexity and experimental simplicity in the context of medicinal chemistry projects.This work was financially supported by the Galician Government (Spain), Projects: 09CSA016234PR and GPC-2014-PG037. J.A. thanks FUNDAYACUCHO (Venezuela) for a predoctoral grant and Deputación da Coruña (Spain) for a postdoctoral research grant. A.N.-V. thanks the Spanish government for a Ramón y Cajal research contract

    Multicomponent Assembly of Diverse Pyrazin-2(1<i>H</i>)‑one Chemotypes

    No full text
    An expedient and concise Ugi-based approach for the rapid assembly of pyrazin-2­(1<i>H</i>)-one-based frameworks has been developed. This convergent approach encompasses skeletal, functional and stereochemical diversity, exhibiting an unusually high bond-forming efficiency as well as high structure and step economies. The method involves the use of readily available commercial reagents and is an example of the reconciliation of structural complexity with operational simplicity in a time- and cost-effective manner

    Multicomponent Assembly of Diverse Pyrazin-2(1<i>H</i>)‑one Chemotypes

    No full text
    An expedient and concise Ugi-based approach for the rapid assembly of pyrazin-2­(1<i>H</i>)-one-based frameworks has been developed. This convergent approach encompasses skeletal, functional and stereochemical diversity, exhibiting an unusually high bond-forming efficiency as well as high structure and step economies. The method involves the use of readily available commercial reagents and is an example of the reconciliation of structural complexity with operational simplicity in a time- and cost-effective manner

    Copper-Catalyzed Huisgen 1,3-Dipolar Cycloaddition under Oxidative Conditions: Polymer-Assisted Assembly of 4‑Acyl-1-Substituted-1,2,3-Triazoles

    No full text
    We herein document the first example of a reliable copper-catalyzed Huisgen 1,3-dipolar cycloaddition under oxidative conditions. The combined use of two polymer-supported reagents (polystyrene-1,5,7-triaza­bicyclo­[4,4,0]­dec-5-ene/Cu and polystyrene-2-iodoxy­benzamide) overcomes the thermodynamic instability of copper­(I) species toward oxidation, enabling the reliable Cu-catalyzed Huisgen 1,3-dipolar cycloadditions in the presence of an oxidant agent. This polymer-assisted pathway, not feasible under conventional homogeneous conditions, provides a direct assembly of 4-acyl-1-substituted-1,2,3-triazoles, contributing to expand the reliability and scope of Cu­(I)-catalyzed alkyne–azide cycloaddition

    Three-Component Assembly of Structurally Diverse 2‑Aminopyrimidine-5-carbonitriles

    No full text
    An expedient route for the synthesis of libraries of diversely decorated 2-aminopyrimidine-5-carbonitriles is reported. This approach is based on a three-component reaction followed by spontaneous aromatization

    Discovery of Potent and Highly Selective A<sub>2B</sub> Adenosine Receptor Antagonist Chemotypes

    No full text
    Three novel families of A<sub>2B</sub> 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<sub>2B</sub> ligand that exhibits complete selectivity toward A<sub>1</sub>, A<sub>2A</sub>, and A<sub>3</sub> 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<sub>2A</sub> receptor

    Discovery of Potent and Highly Selective A<sub>2B</sub> Adenosine Receptor Antagonist Chemotypes

    No full text
    Three novel families of A<sub>2B</sub> 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<sub>2B</sub> ligand that exhibits complete selectivity toward A<sub>1</sub>, A<sub>2A</sub>, and A<sub>3</sub> 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<sub>2A</sub> receptor

    Discovery of 3,4-Dihydropyrimidin-2(1<i>H</i>)‑ones As a Novel Class of Potent and Selective A<sub>2B</sub> Adenosine Receptor Antagonists

    No full text
    We describe the discovery and optimization of 3,4-dihydropyrimidin-2­(1<i>H</i>)-ones as a novel family of (nonxanthine) A<sub>2B</sub> receptor antagonists that exhibit an unusually high selectivity profile. The Biginelli-based hit optimization process enabled a thoughtful exploration of the structure–activity and structure–selectivity relationships for this chemotype, enabling the identification of ligands that combine structural simplicity with excellent hA<sub>2B</sub> AdoR affinity and remarkable selectivity profiles
    corecore