A5082905681- Cholinesterase and Neurodegenerative Diseases
- Carbohydrate Chemistry and Synthesis
- Computational Drug Discovery Methods
- Synthetic Organic Chemistry Methods
- Chemical synthesis and alkaloids
- Catalytic Alkyne Reactions
- Radical Photochemical Reactions
- Synthesis and biological activity
- Asymmetric Synthesis and Catalysis
- Cyclopropane Reaction Mechanisms
- Nicotinic Acetylcholine Receptors Study
- Catalytic C–H Functionalization Methods
- Alzheimer's disease research and treatments
- Chemical Synthesis and Analysis
- Oxidative Organic Chemistry Reactions
- Synthesis and Biological Evaluation
- Electron Spin Resonance Studies
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Synthesis of Organic Compounds
- Free Radicals and Antioxidants
- Sulfur-Based Synthesis Techniques
- Synthesis of heterocyclic compounds
- Click Chemistry and Applications
- Organic and Inorganic Chemical Reactions
Instituto de Química Orgánica General
2016-2025
Centre for Biomedical Network Research on Rare Diseases
2022-2025
Instituto de Salud Carlos III
2022-2025
Yunnan Normal University
2023
Forschungszentrum Jülich
2023
University of Jiroft
2023
Xiamen University
2023
Shanghai Institute of Organic Chemistry
2023
Chulalongkorn University
2023
Consejo Superior de Investigaciones Científicas
2008-2021
A new family of multitarget molecules able to interact with acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), as well monoamino oxidase (MAO) B, has been synthesized. Novel compounds (3–9) have designed using a conjunctive approach that combines the benzylpiperidine moiety AChE inhibitor donepezil (1) indolyl propargylamino MAO N-[(5-benzyloxy-1-methyl-1H-indol-2-yl)methyl]-N-methylprop-2-yn-1-amine (2), connected through an oligomethylene linker. The most promising hybrid (5)...
The versatile ketone C can be obtained by hydrolyzing cyclooctene B, which is formed in a PtCl2-catalyzed cycloisomerization reaction from the enyne precursor A. A carbene platinum complex invoked process, also represents one of few efficient syntheses functionalized cyclooctanes acyclic precursors. Supporting information for this article available on WWW under http://www.wiley-vch.de/contents/jc_2002/2002/z18566_s.pdf or author. Please note: publisher not responsible content functionality...
Organometallic chemistry provides powerful tools for the stereocontrolled synthesis of heterocycles and carbocycles. The electrophilic transition metals Pt(II) Au(I, III) are efficient catalysts in these transitions promote a variety organic transformations unsaturated precursors. These reactions produce functionalized cyclic acyclic scaffolds natural non-natural products efficiently, under mild conditions, with excellent chemoselectivity. Because strongly substrate-dependent, they versatile...
Novel multifunctional tacrines for Alzheimer's disease were obtained by Ugi-reaction between ferulic (or lipoic acid), a melatonin-like isocyanide, formaldehyde, and tacrine derivatives, according to the antioxidant additive approach in order modulate oxidative stress as therapeutic strategy. Compound 5c has been identified promising permeable agent showing excellent properties, strong cholinesterase inhibitory activity, less hepatotoxicity than tacrine, best neuroprotective capacity, being...
Abstract The therapy of complex neurodegenerative diseases requires the development multitarget‐directed drugs (MTDs). Novel indole derivatives with inhibitory activity towards acetyl/butyrylcholinesterases and monoamine oxidases A/B as well histamine H 3 receptor (H3R) were obtained by optimization neuroprotectant ASS234 incorporating generally accepted H3R pharmacophore motifs. These small‐molecule hits demonstrated balanced activities at targets, mostly in nanomolar concentration range....
We report the theoretical analysis of mechanism intramolecular cyclization biaryl alkynes and allenes, catalyzed by electrophilic transition metal complexes soft Lewis acids. These reactions proceed through initial π-complexation alkyne or allene moiety, which triggers nucleophilic attack arene via an endo- exo-dig pathway in a Friedel−Crafts-type mechanism. In addition, alternative reaction mechanisms have been considered to account for some experimental observations. The computed results...
Tacripyrines (1−14) have been designed by combining an AChE inhibitor (tacrine) with a calcium antagonist such as nimodipine and are targeted to develop multitarget therapeutic strategy confront AD. selective potent inhibitors in the nanomolar range. The mixed type inhibition of hAChE activity compound 11 (IC50 105 ± 15 nM) is associated 30.7 8.6% proaggregating action on Aβ moderate self-aggregation (34.9 5.4%). Molecular modeling indicates that binding PAS mainly involves (R)-11...
In this work we describe the synthesis and biological evaluation of tacrine-1,4-dihydropyridine (DHP) hybrids (3-11). These multipotent molecules are result juxtaposition an acetylcholinesterase inhibitor (AChEI) such as tacrine (1) a 1,4-DHP nimodipine (2). Compounds 3-11 very selective potent AChEIs show excellent neuroprotective profile moderate Ca2+ channel blockade effect. Consequently, these new potential drugs for treatment Alzheimer's disease.
The complex nature of Alzheimer's disease (AD) has prompted the design Multi-Target-Directed Ligands (MTDL) able to bind diverse biochemical targets involved in progress and development disease. In this context, we have designed a number MTD propargylamines showing antioxidant, anti-beta-amyloid, anti-inflammatory, as well cholinesterase monoamine oxidase inhibition capacities. Here, describe these properties MTDL ASS234, our lead-compound ready enter pre-clinical studies for AD, new...
Abstract Herein we describe the design, multicomponent synthesis, and biological, molecular modeling ADMET studies, as well in vitro PAMPA‐blood–brain barrier (BBB) analysis of new tacrine–ferulic acid hybrids (TFAHs). We identified ( E )‐3‐(hydroxy‐3‐methoxyphenyl)‐ N ‐{8[(7‐methoxy‐1,2,3,4‐tetrahydroacridin‐9‐yl)amino]octyl}‐ ‐[2‐(naphthalen‐2‐ylamino)2‐oxoethyl]acrylamide (TFAH 10 n ) a particularly interesting multipotent compound that shows moderate completely selective inhibition human...