A5000329987- Multicomponent Synthesis of Heterocycles
- Click Chemistry and Applications
- Chemical Synthesis and Analysis
- Synthesis and biological activity
- Protein Degradation and Inhibitors
- Ion Channels and Receptors
- Synthesis and Biological Evaluation
- Ubiquitin and proteasome pathways
- Peptidase Inhibition and Analysis
- Cyclization and Aryne Chemistry
- Chemical Reactions and Isotopes
- Histone Deacetylase Inhibitors Research
- Tryptophan and brain disorders
- Catalytic Alkyne Reactions
- Catalytic C–H Functionalization Methods
- Bioactive Compounds and Antitumor Agents
- Pharmacogenetics and Drug Metabolism
- Pharmacological Receptor Mechanisms and Effects
- Monoclonal and Polyclonal Antibodies Research
- Herbal Medicine Research Studies
- Synthesis and Characterization of Heterocyclic Compounds
- Synthesis and Catalytic Reactions
- Quinazolinone synthesis and applications
- Mass Spectrometry Techniques and Applications
- Synthetic Organic Chemistry Methods
Università degli Studi del Piemonte Orientale “Amedeo Avogadro”
2016-2025
Istituto di Farmacologia Traslazionale
2015-2017
University of Edinburgh
2012
Institut de Chimie des Substances Naturelles
2006-2010
Centre National de la Recherche Scientifique
2006-2010
University of Milan
2006
Resveratrol is a phytoalexin able to display an array of biological activities. We decided replace the double bond with triazole ring using archetypical click reaction: Huisgen [3 + 2] cycloaddition. Seventy-two derivatives were synthesized via parallel combinatorial approach. Preliminary data suggest that this procedure can lead synthesis compounds some, but not all, resveratrol's actions increased potency.
Abstract PI3K activation plays a central role in the development of pulmonary inflammation and tissue remodeling. inhibitors may thus offer an improved therapeutic opportunity to treat non-resolving lung but their action is limited by unwanted on-target systemic toxicity. Here we present CL27c, prodrug pan-PI3K inhibitor designed for local therapy, investigate whether inhaled CL27c effective asthma fibrosis. Mice inhaling show reduced insulin-evoked Akt phosphorylation lungs, no change other...
By combining three appropriately designed simple substrates, a programmed sequence involving an α-isocyano acetamide-based three-component reaction followed by copper-catalyzed intramolecular [3+2] cycloaddition of alkyne and azide took place to afford complex macrocycles in moderate good yields. One macrocycle two heterocycles were produced with concurrent formation five chemical bonds this operationally process.
Combretastatin A-4 (CA-4) is a potent tubulin depolymerizing agent able to inhibit tumor growth and with antivascular effects. Although it in clinical trials, the search for novel analogues that may display better/different features still ongoing. In this manuscript we describe synthesis of constrained CA-4 obtained only two synthetic steps exploiting regioselective Suzuki coupling dihalogenated heteroaromatic alicyclic compounds. All compounds synthesized have been evaluated cytotoxicity...
The use of small molecules to induce targeted protein degradation is increasingly growing in the drug discovery landscape, and degraders have progressed rapidly through pipelines. Despite advances made so far, their synthesis still represents a significant burden new approaches are highly demanded. Herein we report an unprecedented platform that leverages modular nature both multicomponent reactions enable preparation decorated PROTACs. As proof principle, our has been applied potential...
Acyl chlorides and alpha-isocyanoacetamides undergo an efficient reaction in dichloromethane the presence of triethylamine to give 2-acyl-5-aminooxazoles. Subsequent acid hydrolysis 5-aminooxazole moiety leads alpha-ketoamides good overall yields.
Aryne arylation: A new method of direct arylation is reported for aniline substrates. The reaction uses benzyne to synthesize a variety aminobiaryls under mild conditions (see scheme), requiring no stoichiometric metalation or transition-metal catalysis. An ene mechanism implicated, and conveys excellent functional group tolerance relative metal-mediated processes. Detailed facts importance specialist readers are published as "Supporting Information". Such documents peer-reviewed, but not...
In this study, a successful medicinal chemistry campaign that exploited virtual, biophysical, and biological investigations led to the identification of novel class IDO1 inhibitors based on benzimidazole substructure. This family compounds is endowed with an extensive bonding network in protein active site, including interaction pocket C, region not commonly by previously reported inhibitors. The tight packing selected within enzyme contributes strong binding IDO1, inhibitory potency at low...
Here, we report for the first time a series of compounds potentially useful management oxaliplatin-induced neuropathy (OINP) able to modulate human Carbonic Anhydrases (hCAs) as well Transient Receptor Potential Vanilloid 1 (TRPV1). All showed effective in vitro inhibition activity toward main hCAs involved such pathology, whereas selected items reported moderate agonism TRPV1. X-ray crystallographic experiments assessed binding modes two enantiomers (R)-37a and (S)-37b within hCA II cleft....
Among the various strategies being developed in field of protein degraders, HyTags remain relatively underexplored, despite their advantages over PROTACs. Their synthesis typically involves multistep procedures, including use coupling reagents and protection/deprotection steps. To develop a more sustainable streamlined approach, we designed versatile multicomponent platform that generates with diverse linkers hydrophobic moieties high yields. Using (+)-JQ1 as POI ligand, synthesized series...
Splitting the amine! The Ugi four-component reaction (Ugi 4CR) relies on presence of a component with primary amino group. This protocol has been modified by "splitting" amine into two secondary amines. resulting variant 4CR proceeds good to excellent yield and widens versatility original multicomponent enabling variation molecular backbone.
A three-component reaction of an α,α-disubstituted α-isocyanoacetamide, aldehyde and amino alcohol afforded the 5-iminooxazoline, which, upon saponification, cyclized under acidic conditions to provide macrocyclodepsipeptide in good overall yield.
The synthesis of nonsymmetrical polyamines (PAs) has, up to now, been problematic due lengthy synthetic procedures, lack regioselectivity, and very poor atom economy. An innovative protocol for PAs using a modified Ugi reaction (N-split Ugi) which simplifies the these tricky compounds is described. We believe that this new may open door generation pharmacologically active PAs.
Despite being an old molecule, capsaicin is still a hot topic in the scientific community, and development of new capsaicinoids promising pharmacological approach management skin disorders related to inflammation pruritus. Here we report synthesis evaluation soft drugs that undergo deactivation by hydrolyzing activity esterases. The implanting ester group lipophilic moiety Passerini multicomponent reaction affords both agonists antagonists retain transient receptor potential vanilloid 1...