PROTACs bearing piperazine-containing linkers: what effect on their protonation state?

Proteolysis targeting chimeras (PROTACs) represent an emerging class of compounds for innovative therapeutic application. Their bifunctional nature induces the formation of a ternary complex (target protein/PROTAC/E3 ligase) which allows target protein ubiquitination and subsequent proteasomal-dependent degradation. To date, despite great efforts being made to improve their biological efficacy PROTACs rational design still represents a challenging task, above all for the modulation of their physicochemical and pharmacokinetics properties.

Palladium-Catalyzed Carbonylative Synthesis of Aryl Selenoesters Using Formic Acid as an CO Source.

A new catalytic protocol for the synthesis of selenoesters from aryl iodides and diaryl diselenides has been developed, where formic acid was employed as an efficient, low-cost, and safe substitute for toxic and gaseous CO. This protocol presents a high functional group tolerance, providing access to a large family of selenoesters in high yields (up to 97%) while operating under mild reaction conditions, and avoids the use of selenol which is difficult to manipulate, easily oxidizes, and has a bad odor. Additionally, this method can be efficiently extended to the synthesis of thioesters with moderate-to-excellent yields, by employing for the first time diorganyl disulfides as precursors.

Recent advances in urea- and thiourea-containing compounds: focus on innovative approaches in medicinal chemistry and organic synthesis.

Urea and thiourea represent privileged structures in medicinal chemistry. Indeed, these moieties constitute a common framework of a variety of drugs and bioactive compounds endowed with a broad range of therapeutic and pharmacological properties. Herein, we provide an overview of the state-of-the-art of urea and thiourea-containing pharmaceuticals.

Ebselen and Analogues: Pharmacological Properties and Synthetic Strategies for Their Preparation.

Ebselen is the leader of selenorganic compounds, and starting from its identification as mimetic of the key antioxidant enzyme glutathione peroxidase, several papers have appeared in literature claiming its biological activities. It was the subject of several clinical trials and it is currently in clinical evaluation for the treatment of COVID-19 patients. Given our interest in the synthesis and pharmacological evaluation of selenorganic derivatives with this review, we aimed to collect all the papers focused on the biological evaluation of ebselen and its close analogues, covering the timeline between 2016 and most of 2021.

Seleno-Functionalization of Quercetin Improves the Non-Covalent Inhibition of M and Its Antiviral Activity in Cells against SARS-CoV-2.

The development of new antiviral drugs against SARS-CoV-2 is a valuable long-term strategy to protect the global population from the COVID-19 pandemic complementary to the vaccination. Considering this, the viral main protease (M) is among the most promising molecular targets in light of its importance during the viral replication cycle. The natural flavonoid quercetin has been recently reported to be a potent M inhibitor in vitro, and we explored the effect produced by the introduction of organoselenium functionalities in this scaffold.

Synthesis of 4-Arylselanyl-1-1,2,3-triazoles from Selenium-Containing Carbinols.

In this work, we present a simple way to achieve 4-arylselanyl-1-1,2,3-triazoles from selenium-containing carbinols in a one-pot strategy. The selenium-containing carbinols were used as starting materials to produce a range of selanyl-triazoles in moderate to good yields, including a quinoline and Zidovudine derivatives. One-pot protocols are crucial to the current concerns about waste production and solvent consumption, avoiding the isolation and purification steps of the reactive terminal selanylalkynes.

Flow Biocatalysis: A Challenging Alternative for the Synthesis of APIs and Natural Compounds.

Biocatalysts represent an efficient, highly selective and greener alternative to metal catalysts in both industry and academia. In the last two decades, the interest in biocatalytic transformations has increased due to an urgent need for more sustainable industrial processes that comply with the principles of green chemistry. Thanks to the recent advances in biotechnologies, protein engineering and the Nobel prize awarded concept of direct enzymatic evolution, the synthetic enzymatic toolbox has expanded significantly.

A Simple Zinc-Mediated Method for Selenium Addition to Michael Acceptors.

In this work, we focused our attention on seleno-Michael type reactions. These were performed using zinc-selenolates generated in situ from diphenyl diselenide , 1,2-bis(3-phenylpropyl)diselenide , and protected selenocystine via an efficient biphasic Zn/HCl-based reducing system. Alkenes with a variety of electron-withdrawing groups were investigated in order to gauge the scope and limitations of the process.

Organic Diselenides: Versatile Reagents, Precursors, and Intriguing Biologically Active Compounds.

In this account, we describe how some organic diselenides were successfully used in the past as reagents for asymmetric stereoselective synthesis and more recently as precursors of catalysts and reagents applied in new green protocols. A biomimetic approach offered the possibility to perform oxidative reactions using hydrogen peroxide as oxidant and water as medium affording the desired products in excellent yields under mild conditions. The umpolung of the selenium atom gave novel nucleophilic reagents having a strongly accelerated reaction rate in on water conditions.