1,4-Dioxins, Oxathiins, Dithiins and Their Benzo Derivatives

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An overview on the synthesis and anticancer properties of ethacrynic acid and their analogues

Ethacrynic acid (EA, Edecrin) is a well-known diuretic drug used in the treatment of high blood pressure and the swelling caused by diseases such as congestive heart failure, liver failure, and kidney failure. EA has an α,β-unsaturated carbonyl unit which acts as a Michael acceptor involved in the inhibition of the major classes of glutathione S-transferases (GSTs) (α, μ, and π) that plays a crucial role in regulating the multidrug resistance. Moreover, EA was used as an adjuvant to improve the therapeutic efficacy of several anticancer chemotherapeutic agents. EA and their derivatives have received considerable attention in the past decades due to their interesting biological properties. This review highlights the recent development in this area, focusing on their synthesis and their antitumor activities

Synthèse de divers hétérocycles sur support polymère à partir d'un synthon commun (élaboration et évaluation pharmacologique de ligands mélatoninergiques à structure imidazo[1,2-a]pyridinique)

Ce travail se divise en deux parties : La première est consacrée à la synthèse sur support polymère de divers hétérocycles à partir d'un synthon commun. Dans cet esprit, une méthode originale permettant de générer une a-bromocétone est développée. Par la suite, cette entité est utilisée pour la préparation de thiazoles, d'imidazo[1,2-a]pyridines et pyrimidines en chauffage classique et sous irradiation micro-ondes. Afin d'obtenir des composés diversement fonctionnalisés, plusieurs réactions ont été optimisées sur phase solide telles que les séquences de couplage catalysées par le palladium. La deuxième partie est réservée à la préparation de nouveaux ligands mélatoninergiques. Dans ce cadre, deux synthèses ont été mises au point conduisant à des analogues de la 2-phénylmélatonine à structure imidazo[1,2-a]pyridinique. Deux composés sur lesquels des chaînes amide ou rétroamide sont introduites ont été élaborés et ont fait l'objet d'études pharmacologiques.ORLEANS-BU Sciences (452342104) / SudocSudocFranceF

Unlocking the Potential of Deep Eutectic Solvents for C–H Activation and Cross-Coupling Reactions: A Review

Green chemistry principles have underpinned the development of deep eutectic solvents (DESs). In this brief overview, we discuss the potential of DESs as a greener alternative to volatile organic solvents for cross-coupling and C–H activation reactions in organic chemistry. DESs offer numerous benefits, such as easy preparation, low toxicity, high biodegradability, and the potential to replace volatile organic compounds. The ability of DESs to recover the catalyst-solvent system enhances their sustainability. This review highlights recent advances and challenges in utilizing DESs as a reaction media, as well as the impact of physicochemical properties on the reaction process. Several types of reactions are studied to highlight their effectiveness at promoting C–C bond formation. Aside from demonstrating the success of DESs in this context, this review also discusses the limitations and future prospects of DESs in organic chemistry

Dendrimer space concept for innovative nanomedicine: A futuristic vision for medicinal chemistry

International audienceOver the last decade, various nanomaterial systems have been developed as important and powerful strategies to deliver conventional drugs, recombinant proteins, vaccines, aptamers, siRNA, nucleotides and genes. In particular, alongside polymeric, solid–lipid, magnetic and metal based nanoparticles, polymeric micelles and linear polymers, dendrimer nanostructures represent useful nano-carriers in medicine. Today's challenge to find safe and innovative drugs remains as critical as ever.In this review, for the first time, we define the term dendrimer space concept as an approach that affords a new paradigm of thought for medicinal chemists and opens new and promising avenues toward the identification of original dendrimer-based drugs. Thus, the dendrimer space defines a new ‘druggable’ cluster that is included within the vast volume of chemical space. The dendrimer space concept took its inspiration from both the concepts of ‘druglikeness’ and ‘druggability’, which are fully and practically integrated into the drug discovery process, and from different methods of exploration and navigation, such as the ‘chemography’ approach, in chemical space. It was further influenced by the large number of biomedical applications using dendrimers that were developed from only a handful existing in the early 1990s.To define the boundaries of the dendrimer space, this review first focuses on the recent progress in the exploration of specific sub-chemical spaces (clusters within the continuum of chemical space). Chemical space is defined as the entire collection of all meaningful chemical compounds, and its full examination is insuperable. The compounds included in these different clusters can be mapped onto the coordinates of a multidimensional descriptor space, with such variables as physicochemical properties or topological characteristics, and are based on the concepts of ‘druglikeness’ (drug-like space) and ‘leadlikeness’. In addition, the discrete areas occupied by specific biologically active compounds define the boundaries of the ‘target class’ clusters, which can overlap the drug-like space. Second, this review gives an overview of the nanopharmaceutical properties of dendrimers, both as biologically active derivatives per se and as drug delivery systems. Finally, several perspectives using dendrimers as new delivery platforms based on the concept of dendrimer space are presented

Synthesis and evaluation of a novel class of ethacrynic acid derivatives containing triazoles as potent anticancer agents

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“On Water” Palladium Catalyzed Direct Arylation of 1H-Indazole and 1H-7-Azaindazole

The C3 direct arylation of 1H-indazole and 1H-7-azaindazole has been a significant challenge due to the lack of the reactivity at this position. In this paper, we describe a mild and an efficient synthesis of new series of C3-aryled 1H-indazoles and C3-aryled 1H-7-azaindazoles via a C3 direct arylation using water as solvent. On water, PPh3 was effective as a ligand along with a lower charge of the catalyst Pd(OAc)2 (5 mol%) at 100 °C, leading to C3-aryled 1H-indazoles or C3-aryled 1H-7-azaindazoles in moderate to good yields