Identification and study of new NF-κB-inducing kinase ligands derived from the imidazolone scaffold.

Chronic kidney disease (CKD) is a growing health concern, projected to be a major cause of death by 2040, due to an increasing risk of acute kidney injury (AKI). Systems biology-derived data suggest that the unmet need for an orally available drug to treat AKI and improve CKD outcomes may be addressed by targeting kidney inflammation and, specifically, nuclear factor κB-inducing kinase (NIK), a key signaling molecule that activates the noncanonical nuclear factor κB (NF-κB) pathway. We have prepared and identified a small family of imidazolone derivatives that bind NIK and inhibit the noncanonical NF-κB activation pathway.

Selective Synthesis of Boron-Functionalized Indenes and Benzofulvenes by BCl-Promoted Cyclizations of -Alkynylstyrenes.

A selective, metal-free synthesis of boron-functionalized indenes and benzofulvenes via BCl-mediated cyclization of -alkynylstyrenes is described. The method allows precise control over product formation by adjusting reaction conditions. These borylated products were utilized in diverse C-B bond derivatizations and in the total synthesis of Sulindac, a nonsteroidal anti-inflammatory drug, demonstrating the versatility and practicality of the developed methodology for synthetic applications.

Synthesis of Seven- and Eight-Membered Rings by a Brønsted Acid Catalyzed Cationic Carbocyclization of Biphenyl Embedded Enynes.

A Brønsted acid catalyzed cyclization of -alkenyl--alkynylbiaryls for the synthesis of biologically relevant dibenzo-fused medium-sized rings has been developed. The outcome of the cyclization is determined by the nature of the substituent at the alkyne, with arenes favoring seven-membered rings and alkyl substituents producing eight-membered rings. These reactions proceed via a vinyl cation, which is captured by water and, notably, by C-nucleophiles, such as electron-rich (hetero)arenes.

Validation of the RIM Score-COVID in the Spanish SEMI-COVID-19 Registry.

The significant impact of COVID-19 worldwide has made it necessary to develop tools to identify patients at high risk of severe disease and death. This work aims to validate the RIM Score-COVID in the SEMI-COVID-19 Registry. The RIM Score-COVID is a simple nomogram with high predictive capacity for in-hospital death due to COVID-19 designed using clinical and analytical parameters of patients diagnosed in the first wave of the pandemic.

Metal-Free Temperature-Controlled Regiodivergent Borylative Cyclizations of Enynes: BCl -Promoted Skeletal Rearrangement.

Metal-free borylative cyclization of biphenyl-embedded 1,3,5-trien-7-ynes in the presence of simple and inexpensive BCl provided synthetically useful borylated building blocks. The outcome of the process depends on the reaction temperature, with borylated phenanthrenes obtained at 60 °C and phenanthrene-fused borylated cyclobutanes formed at 0 °C. Based on DFT calculations, a mechanism for these novel transformations has been proposed, which involves an uncommon skeletal rearrangement, including migration of a methyl group and alkyne fragmentation, unprecedented in BCl -promoted cyclization reactions.