A5024020550- Receptor Mechanisms and Signaling
- Catalytic C–H Functionalization Methods
- Catalytic Cross-Coupling Reactions
- Neurotransmitter Receptor Influence on Behavior
- Cancer, Lipids, and Metabolism
- SARS-CoV-2 and COVID-19 Research
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- COVID-19 Clinical Research Studies
- Neuropeptides and Animal Physiology
- Asymmetric Hydrogenation and Catalysis
- Pharmacological Receptor Mechanisms and Effects
- Computational Drug Discovery Methods
- Chemical Synthesis and Analysis
- Diabetes Treatment and Management
- Peroxisome Proliferator-Activated Receptors
- Adipose Tissue and Metabolism
- Virus-based gene therapy research
- Lipid metabolism and biosynthesis
- Cyclopropane Reaction Mechanisms
- Oxidative Organic Chemistry Reactions
- Inflammatory mediators and NSAID effects
- Cytokine Signaling Pathways and Interactions
- Pancreatic function and diabetes
- Chemical synthesis and alkaloids
University of Bristol
2018-2024
Universidad Complutense de Madrid
2012-2022
Centro de Investigaciones Biológicas Margarita Salas
2020-2021
The activation of σ-bonds by transition metals underpins a wide range methods for the synthesis complex molecules. Within this context, C–N bond has emerged recently as powerful strategy preparation or utilization nitrogen-containing compounds, due to prevalence bonds in organic compounds. A key challenge area is that most are relatively inert, and makes their difficult task. Since turn millennium number published articles regarding grown exponentially, providing important improvements...
Upregulation of fatty acid synthase (FASN) is a common event in cancer, although its mechanistic and potential therapeutic roles are not completely understood. In this study, we establish key role FASN during transformation. required for eliciting the anaplerotic shift Krebs cycle observed cancer cells. However, main to consume acetyl-CoA, which unlocks isocitrate dehydrogenase (IDH)-dependent reductive carboxylation, producing power necessary quench reactive oxygen species (ROS) originated...
Fatty acid synthase (FASN) is a lipogenic enzyme that highly expressed in different human cancers. Here we report the development of new series polyphenolic compounds 5-30 have been evaluated for their cytotoxic capacity SK-Br3 cells, breast cancer cell line with high FASN expression. The an IC(50) < 50 μM tested ability to inhibit activity. Among them, derivative 30 blocks 90% activity at low concentration (4 μM), broad panel tumor induces apoptosis, and activation HER2, AKT, ERK pathways....
The unprecedent situation generated by the COVID-19 global emergency has prompted us to actively work fight against this pandemic searching for repurposable agents among FDA approved drugs shed light into immediate opportunities treatment of patients. In attempt proceed toward a proper rationalization search new antivirals drugs, we carried out hierarchical in silico/in vitro protocol which successfully combines virtual and biological screening speed up identification host-directed therapies...
Serotonin 5-HT6 receptor has been proposed as a promising therapeutic target for cognition enhancement though the development of new antagonists is still needed to validate these molecules drug class treatment Alzheimer's disease and other pathologies associated with memory deficiency. As part our efforts receptor, benzimidazole-based compounds have designed synthesized. Site-directed mutagenesis homology models show importance halogen bond interaction between chlorine atom identified herein...
The 5-HT2CR agonist lorcaserin, clinically approved for the treatment of obesity, causes important side effects mainly related to subtype selectivity. In search allosteric modulators as safer antiobesity drugs, a chemical library from Vivia Biotech was screened using ExviTech platform. Structural modifications identified hit VA240 in synthesized analogues 6–41 afforded compound 11 (N-[(1-benzyl-1H-indol-3-yl)methyl]pyridin-3-amine, VA012), which exhibited dose-dependent enhancement serotonin...
Structurally complex benzo- and spiro-fused N-polyheterocycles can be accessed via intramolecular Pd(0)-catalyzed alkene 1,2-aminoarylation reactions. The method uses N-(pentafluorobenzoyloxy)carbamates as the initiating motif, this allows aza-Heck-type amino-palladation in advance of C–H palladation aromatic component. chemistry is showcased first total synthesis alkaloid (+)-pileamartine A, which has resulted reassignment its absolute stereochemistry.
Peptidic agonists of the glucagon-like peptide-1 receptor (GLP-1R) have gained a prominent role in therapy type-2 diabetes and are being considered for reducing food intake obesity. Potential advantages small molecules acting as positive allosteric modulators (PAMs) GLP-1R, including oral administration reduced unwanted effects, could improve utility this class drugs. Here, we describe discovery compound 9...
We report a strategy for the C‐N cross‐coupling of tertiary amines via in situ generation and displacement N‐acyl ammonium species. Specifically, treatment diverse with TFAA or choroformates presence NaI leads to efficient alkyl iodides, which can be engaged directly Ni‐catalyzed cross‐couplings. The protocol is applicable acyclic cyclic systems, including highly hindered variants. Applications late‐stage modification complex heterocycles are presented.
Tolerance development caused by dopamine replacement with l-DOPA and therapeutic drawbacks upon activation of dopaminergic receptors orthosteric agonists reveal a significant unmet need for safe effective treatment Parkinson's disease. In search selective modulators the D1 receptor, screening chemical library subsequent medicinal chemistry program around an identified hit resulted in new synthetic compound 26 [UCM-1306, 2-(fluoromethoxy)-4′-(S-methanesulfonimidoyl)-1,1′-biphenyl] that...
Abstract We report a strategy for the formal C−N cross‐coupling of tertiary amines via in situ generation and displacement N‐acyl ammonium species. Specifically, treatment diverse with TFAA or chloroformates presence NaI leads to efficient alkyl iodides, which can be engaged directly Ni‐catalyzed cross‐couplings. The protocol is applicable acyclic cyclic systems, including highly hindered variants. Applications late‐stage modification complex heterocycles are presented.
Abstract The unprecedent situation generated by the COVID-19 global emergency prompted us to actively work fight against this pandemic searching for repurposable agents among FDA approved drugs shed light into immediate opportunities treatment of patients. In attempt proceed toward a proper rationalization search new antivirals drugs, we carried out hierarchical in silico/in vitro protocol which successfully combines virtual and biological screening speed up identification host-directed...