A5075652944- Synthesis and Reactivity of Heterocycles
- Adenosine and Purinergic Signaling
- Receptor Mechanisms and Signaling
- Synthesis and Biological Evaluation
- Synthesis and biological activity
- Synthesis and Characterization of Heterocyclic Compounds
- Synthesis and Reactions of Organic Compounds
- Chemical Synthesis and Analysis
- Phenothiazines and Benzothiazines Synthesis and Activities
- Crystallization and Solubility Studies
- Pharmacological Receptor Mechanisms and Effects
- X-ray Diffraction in Crystallography
- Multicomponent Synthesis of Heterocycles
- Click Chemistry and Applications
- Neuropeptides and Animal Physiology
- Migraine and Headache Studies
- Quinazolinone synthesis and applications
- Psychosomatic Disorders and Their Treatments
- Cannabis and Cannabinoid Research
- Neurotransmitter Receptor Influence on Behavior
- Phosphodiesterase function and regulation
- Neuroscience and Neuropharmacology Research
- Monoclonal and Polyclonal Antibodies Research
- Chemical synthesis and pharmacological studies
- Chemical Synthesis and Reactions
Universidade de Santiago de Compostela
2016-2025
Center for Research in Molecular Medicine and Chronic Diseases
2015-2025
Centro Singular de Investigación en Química Biológica y Materiales Moleculares
2010-2021
Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria
2021
Hospital Clínico Universitario de Valladolid
2014-2020
Universidad de Valladolid
2018-2019
Uppsala University
2017
Centro de Investigación en Sanidad Animal
2013
Centro Regional de Selección y Reproducción Animal
2013
Institute of Industrial Organic Chemistry
2010
Two 3D-hybrid monolithic catalysts containing immobilized copper and palladium species on a silica support were synthesized by 3D printing subsequent surface functionalization protocol. The resulting monoliths provided structure with pore sizes around 300 μm, high mechanical strength, easy catalyst recyclability. devices designed to perform heterogeneous multicatalytic multicomponent reactions (MMCRs) based alkyne–azide cycloaddition (CuAAC) + catalyzed cross-coupling (PCCC) strategy, which...
Three novel families of A2B adenosine receptor antagonists were identified in the context structural exploration 3,4-dihydropyrimidin-2(1H)-one chemotype. The most appealing series contain imidazole, 1,2,4-triazole, or benzimidazole rings fused to 2,3-positions parent diazinone core. optimization process enabled identification a highly potent (3.49 nM) ligand that exhibits complete selectivity toward A1, A2A, and A3 receptors. results functional cAMP experiments confirmed antagonistic...
Pancreatic cancer (PC) is an aggressive subtype presenting unmet clinical challenges. Conventional chemotherapy, which includes antimetabolite gemcitabine (GEM), seriously undermined by a short half-life, its lack of targeting ability, and systemic toxicity. GEM incorporation in self-assembled nanosystems still underexplored due to GEM’s hydrophilicity hinders efficient encapsulation. We hypothesized that vitamin E succinate–GEM prodrug (VES-GEM conjugate) combines hydrophobicity...
Abstract New supported catalysts for the Huisgen’s [3+2] azide‐alkyne cycloaddition have been prepared by immobilization of copper species on commercially available polymeric matrixes incorporating 1,5,7‐triazabicyclo[4.4.0]dec‐5‐ene (TBD) template. The synergic exploitation exceptional chelating ability and basicity profile TBD framework, in addition to ensuring effective stabilization species, allows implementation three‐component strategies. new catalytic systems enabled development...
We describe the discovery and optimization of 3,4-dihydropyrimidin-2(1H)-ones as a novel family (nonxanthine) A2B receptor antagonists that exhibit an unusually high selectivity profile. The Biginelli-based hit process enabled thoughtful exploration structure-activity structure-selectivity relationships for this chemotype, enabling identification ligands combine structural simplicity with excellent hA2B AdoR affinity remarkable profiles.
Two regioisomeric series of diaryl 2- or 4-amidopyrimidines have been synthesized and their adenosine receptor affinities were determined in radioligand binding assays at the four human receptors (hARs). Some ligands prepared herein exhibit remarkable (Ki < 10 nm) and, most noticeably, absence activity A1, A2A, A2B receptors. The structural determinants that support affinity selectivity profiles highlighted through an integrated computational approach, combining a 3D-QSAR model built on...
Blood/brain-glutamate grabbing is an emerging concept in the treatment of acute ischemic stroke, where essentially deleterious effects glutamate after ischemia are ameliorated by coaxing to enter bloodstream and thus reducing its concentration brain. Aiming demonstrate clinical efficacy blood grabbers patients with this study, we resorted a drug-repositioning strategy for discovery new glutamate-grabbing drugs.The ability 1,120 compounds (90% which were drugs approved US Food Drug...
We have here assessed, using Δ9-tetrahydrocannabinol (Δ9-THC) for comparison, the effect of Δ9-tetrahydrocannabinolic acid (Δ9-THCA) and Δ9-tetrahydrocannabivarin (Δ9-THCV) that is mediated by human versions CB1, CB2, CB1-CB2 receptor functional units, expressed in a heterologous system. Binding to CB1 CB2 receptors was addressed living cells means homogeneous assay. A biphasic competition curve binding receptor, obtained Δ9-THCV expressing two receptors. Signaling studies included cAMP...
A practical, integrated and versatile U-4CR-based assembly of 1,4-benzodiazepin-2-ones exhibiting functionally, skeletally, stereochemically diverse substitution patterns is described. By virtue its convergence, atom economy, bond-forming efficiency, the methodology documented herein exemplifies reconciliation structural complexity experimental simplicity in context medicinal chemistry projects.
The four receptors that signal for adenosine, A₁, A2A, A2B and A₃ ARs, belong to the superfamily of G protein-coupled (GPCRs). They mediate a number (patho)physiological functions have attracted interest biopharmaceutical sector decades as potential drug targets. many crystal structures lately A₁ allow use advanced computational, structure-based ligand design methodologies. Over last decade, we assessed efficient synthesis novel ligands specifically addressed each ARs. We herein review...
We present and thoroughly characterize a large collection of 3,4-dihydropyrimidin-2(1H)-ones as A2BAR antagonists, an emerging strategy in cancer (immuno) therapy. Most compounds selectively bind A2BAR, with number potent selective antagonists further confirmed by functional cyclic adenosine monophosphate experiments. The series was analyzed one the most exhaustive free energy perturbation studies on GPCR, obtaining accurate model structure–activity relationship this chemotype....
We present a robust protocol based on iterations of free energy perturbation (FEP) calculations, chemical synthesis, biophysical mapping and X-ray crystallography to reveal the binding mode an antagonist series A2A adenosine receptor (AR). Eight AR site mutations from experiments were initially analyzed with sidechain FEP simulations, performed alternate modes. The results distinctively supported one mode, which was subsequently used design new chromone derivatives. Their affinities for...
A systematic exploration of bioisosteric replacements for furan and thiophene cores in a series potent A2BAR antagonists has been carried out using the nitrogen-walk approach. collection 42 novel alkyl 4-substituted-2-methyl-1,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-3-carboxylates, which contain 18 different pentagonal heterocyclic frameworks at position 4, was synthesized evaluated. This study enabled identification new ligands that combine remarkable affinity (Ki < 30 nM) exquisite...
A novel family of structurally simple, potent, and selective nonxanthine A2BAR ligands was identified, its antagonistic behavior confirmed through functional experiments. The reported alkyl 2-cyanoimino-4-substituted-6-methyl-1,2,3,4-tetrahy-dropyrimidine-5-carboxylates (16) were designed by bioisosteric replacement the carbonyl group at position 2 in a series 3,4-dihydropyrimidin-2-ones. scaffold documented herein contains chiral center heterocycle. Accordingly, most attractive ligand...