Regioselective Copper(I)-Catalyzed Direct C(3)-H (Hetero)arylation of 6-(Hetero)arylated 1,2,4-Triazolo[4,3-]pyridazines: Ligand-Free Approach.

The first efficient Cu(I) catalyzed regioselective C3-(hetero)arylation of 6-(hetero)arylated 1,2,4-triazolo[4,3-]pyridazines has been developed to streamline the synthesis of pharmaceutically important 3,6-diarylated 1,2,4-triazolo[4,3-]pyridazines. This direct (hetero)arylation is compatible with a range of aryl iodides and tolerates a variety of functional groups (23 examples). A series of new 3,6-diarylated 1,2,4-triazolo[4,3-]pyridazines were synthesized with good to excellent yields (up to 98%).

Experimental and theoretical approach for a better understanding of the mechanisms of adsorption and inhibition of corrosion for carbon steel by thiazolidine derivatives in 1 M HCl medium.

Many sectors have employed various strategies to prolong the life of steel because of its strength and high manufacturing and installation costs. The use of organic inhibitors has been widespread in recent years. The purpose of this investigation is to evaluate the activity of recently synthesized derivatives, namely ()-5-benzylidenethiazolidine-2,4-dione (FT-2a), ()-5-(2,4-dichlorobenzylidene)thiazolidine-2,4-dione (FT-2c), and ()-3-allyl-5-(2,4-dichlorobenzylidene)thiazolidine-2,4-dione (FT-3c), in inhibiting corrosion through electrochemical assays on carbon steel (CS) in 1 M HCl at 303 K.

Assessment of anti-hyperglycemic and anti-hyperlipidemic effects of thiazolidine-2,4-dione derivatives in HFD-STZ diabetic animal model.

Type 2 diabetes mellitus (T2DM) is a chronic endocrine/metabolic disorder characterized by elevated postprandial and fasting glycemic levels that result in disturbances in primary metabolism. In this study, we evaluated the metabolic effects of thiazolidine-2,4-dione derivatives in Wistar rats and Swiss mice that were fed a high-fat diet (HFD) for 4 weeks and received 90 mg/kg of streptozotocin (STZ) intraperitoneally as a T2DM model. The HFD consisted of 17% carbohydrate, 58% fat, and 25% protein, as a percentage of total kcal.

Green synthesis and anti-biofilm activities of 3,5-disubstituted isoxazoline/isoxazole-linked secondary sulfonamide derivatives on Pseudomonas aeruginosa.

The search for new classes of antibiotics is a real concern of public health due to the emergence of multi-resistant bacteria strains. We report herein the synthesis and characterization of a new series of 13 molecules combining isoxazoline/isoxazole sulfonamides and hydrazides motives. These molecules were obtained according to a costless eco-friendly procedure, and a one-pot three-step cascade synthesis under ultrasonic cavitation.

Green synthesis, characterization, and biochemical impacts of new bioactive isoxazoline-sulfonamides as potential insecticidal agents against the Sphodroxia maroccana Ley.

Background: Sphodroxia maroccana Ley is a pest of cork oak crops that damages the roots of seedlings and can severely impair cork oak regeneration. Since the banning of carbosulfan and chlorpyriphos, which were widely used against the larvae of Sphodroxia maroccana because of their harmful impact on the environment, until now there has been no pesticide against these pests. Therefore, it is particularly urgent to develop highly effective insecticidal molecules with novel scaffolds.

Polyacetylenic caffeoyl amides from Ammodaucus leucotrichus.

Six undescribed polyacetylenic caffeoyl amides, five known flavones and three known lignans were obtained from the fruits of the North African traditional medicinal plant Ammodaucus leucotrichus Coss. & Durieu (Apiaceae). Isolation was achieved by a combination of chromatographic methods, and structures were established by extensive 1D and 2D NMR spectroscopy, mass spectrometry, electronic circular dichroism, and by GC-MS analysis of sugar derivatives.

Ultrasound-assisted one-pot three-component synthesis of new isoxazolines bearing sulfonamides and their evaluation against hematological malignancies.

In the present study, following a one-pot two-step protocol, we have synthesized novel sulfonamides-isoxazolines hybrids (3a-r) via a highly regioselective 1,3-dipolar cycloaddition. The present methodology capitalized on trichloroisocyanuric acid (TCCA) as a safe and ecological oxidant and chlorinating agent for the in-situ conversion of aldehydes to nitrile oxides in the presence of hydroxylamine hydrochloride, under ultrasound activation. These nitrile oxides could be engaged in 1,3-dipolar cycloaddition reactions with various alkene to afford the targeted sulfonamides-isoxazolines hybrids (3a-r).

Synthesis, α-glucosidase and α-amylase inhibitory activities, acute toxicity and molecular docking studies of thiazolidine-2,4-diones derivatives.

In the present study, a series of thiazolidine-2,4-diones derivatives () and () were synthesized and characterized by H NMR, C NMR and ESI-MS spectrometry. All compounds were screened for their α-glucosidase and α-amylase inhibitory activities. biological investigations revealed that most of compounds were active against α-glucosidase with IC values in the range of 43.

5-((1H-imidazol-1-yl)methyl)quinolin-8-ol as potential antiviral SARS-CoV-2 candidate: Synthesis, crystal structure, Hirshfeld surface analysis, DFT and molecular docking studies.

A potential new drug to treat SARS-CoV-2 infections and chloroquine analogue, 5-((1H-imidazol-1-yl)methyl)quinolin-8-ol () has been here synthesized and characterized by FT-IR, H-NMR, C-NMR, ultraviolet-visible, ESI-MS and single-crystal X-ray diffraction. was optimized in gas phase, aqueous and DMSO solutions using hybrid B3LYP/6-311++G(d,p) method. Comparisons between experimental and theoretical infrared spectra, H and C NMR chemical shifts and electronic spectrum in DMSO solution evidence good concordances.

Ultrasound-assisted one-pot green synthesis of new N- substituted-5-arylidene-thiazolidine-2,4-dione-isoxazoline derivatives using NaCl/Oxone/NaPO in aqueous media.

A rapid and green method for the synthesis of novel N-thiazolidine-2,4-dione isoxazoline derivatives 5 from N-allyl-5-arylidenethiazolidine-2,4-diones 3 as dipolarophiles with arylnitrile oxides via 1,3-dipolar cycloaddition reaction. The corresponding N-allyl substituted dipolarophiles were prepared by one-pot method from thiazolidine-2,4-dione with aldehydes using Knoevenagel condensation followed by N-allylation of thiazolidine-2,4-dione in NaOH aqueous solution under sonication. In addition, the isoxazoline derivatives 5 were synthesized by regioselective and chemoselective 1,3-dipolar cycloaddition using inexpensive and mild NaCl/Oxone/NaPO as a Cl source, oxidant and/or catalyst under ultrasonic irradiation in EtOH/HO (v/v, 2:1) as green solvent.

Concise synthesis and antibacterial evaluation of novel 3-(1,4-disubstituted-1,2,3-triazolyl)uridine nucleosides.

We report herein a simple and efficient synthesis of a new series of antibacterial uridine nucleosides. The strategy involved a sequential silylation/N-glycosylation/N-propargylation procedure of uracil 1 for preparing the dipolarophile 5 in good yield. A series of novel uridine-[1,2,3]triazole nucleosides 6a-j were efficiently synthesized via the copper-catalyzed azide-alkyne cycloaddition (CuAAC) from dipolarophile 5 with different selected azides.

Modular synthesis of new C-aryl-nucleosides and their anti-CML activity.

The C-aryl-ribosyles are of utmost interest for the development of antiviral and anticancer agents. Even if several synthetic pathways have been disclosed for the preparation of these nucleosides, a direct, few steps and modular approaches are still lacking. In line with our previous efforts, we report herein a one step - eco-friendly β-ribosylation of aryles and heteroaryles through a direct Friedel-Craft ribosylation mediated by bismuth triflate, Bi(OTf).

Ultrasound-assisted facile one-pot sequential synthesis of novel sulfonamide-isoxazoles using cerium (IV) ammonium nitrate (CAN) as an efficient oxidant in aqueous medium.

A series of novel 3,5-disubstituted isoxazoles have been synthesized, using a new, green, and versatile "one-pot three-steps" methodology. The key step is an oxidative 1,3-dipolar cycloaddition under ultrasonic irradiation, occurring in aqueous media, and mediated by cerium (IV) ammonium nitrate (CAN). CAN is a one-electron oxidant, highly soluble in water, slightly toxic and inexpensive, that allows the in situ conversion of the intermediate aldoximes into nitrile oxide.

Synthesis and anti-cancer activities of new sulfonamides 4-substituted-triazolyl nucleosides.

Nucleoside analogues are among the most known drugs commonly used in antiviral and anticancer chemotherapies. Among them, those featuring a five-membered ring nucleobase are of utmost interest such as the anti-cancer agent AICAR or the anti-viral drug ribavirin. Despite its low activity in vitro in different cell lines, AICAR is under clinical development for several pathologies, thanks to its original mode of action.

In Vitro and in Vivo Evaluation of Fully Substituted (5-(3-Ethoxy-3-oxopropynyl)-4-(ethoxycarbonyl)-1,2,3-triazolyl-glycosides as Original Nucleoside Analogues to Circumvent Resistance in Myeloid Malignancies.

A series of nucleoside analogues bearing a 1,4,5-trisubstituted-1,2,3-triazole aglycone was synthesized using a straightforward click/electrophilic addition or click/oxidative coupling tandem procedures. SAR analysis, using cell culture assays, led to the discovery of a series of compounds belonging to the 5-alkynyl-1,2,3-triazole family that exhibits potent antileukemic effects on several hematologic malignancies including chronic myeloid leukemia (CML) and myelodysplastic syndromes (MDS) either sensitive or resistant to their respective therapy. Compound 4a also proved efficient in vivo on mice xenografted with SKM1-R MDS cell line.

Microwave-Assisted Syntheses of Bioactive Seven-Membered, Macro-Sized Heterocycles and Their Fused Derivatives.

This review describes the recent advances in the microwave-assisted synthesis of 7-membered and larger heterocyclic compounds. Several types of reaction for the cyclization step are discussed: Ring Closing Metathesis (RCM), Heck and Sonogashira reactions, Suzuki-Miyaura cross-coupling, dipolar cycloadditions, multi-component reactions (Ugi, Passerini), etc. Green syntheses and solvent-free procedures have been introduced whenever possible.

Microwave-Assisted Synthesis of Bioactive Six-Membered Heterocycles and Their Fused Analogues.

This review describes the formation of six-membered heterocyclic compounds and their fused analogues under microwave activation using modern organic transformations including cyclocondensation, cycloaddition, multicomponents and other modular reactions. The review is divided according to the main heterocycle types in order of increasing complexity, starting with heterocyclic systems containing one, two and three heteroatoms and their fused analogues. Recent microwave applications are reviewed, with special focus on the chemistry of bioactive compounds.

Recent progress in the design, study, and development of c-Jun N-terminal kinase inhibitors as anticancer agents.

The c-Jun N-terminal kinase (JNK) family, with its three members JNK1, JNK2, and JNK3, is a subfamily of mitogen-activated protein kinases. Involved in many aspects of cellular processes, JNK has been also associated with pathological states such as neurodegenerative diseases, inflammation, and cancers. In oncology, each isoform plays a distinct role depending on the context of the targeted tissue/organ, the tumor stage, and, most likely, the signaling pathway activated upstream.

Structural elucidation of the DFG-Asp in and DFG-Asp out states of TAM kinases and insight into the selectivity of their inhibitors.

Structural elucidation of the active (DFG-Asp in) and inactive (DFG-Asp out) states of the TAM family of receptor tyrosine kinases is required for future development of TAM inhibitors as drugs. Herein we report a computational study on each of the three TAM members Tyro-3, Axl and Mer. DFG-Asp in and DFG-Asp out homology models of each one were built based on the X-ray structure of c-Met kinase, an enzyme with a closely related sequence.

FeCl3-promoted and ultrasound-assisted synthesis of resveratrol O-derived glycoside analogs.

Phenol derived O-glycosides were synthesized using a direct and convenient O-glycosidation, starting from acetylated sugars in the presence of FeCl3, an inexpensive, mild and benign Lewis acid catalyst. The reactions were carried out under both conventional and ultrasonic irradiation conditions. In general, improvement in rates and yields were observed when reactions were carried out under sonication compared with conventional conditions leading to the corresponding β-O-glycosides as the major anomer.

Ultrasound-assisted one-pot synthesis of anti-CML nucleosides featuring 1,2,3-triazole nucleobase under iron-copper catalysis.

A simple and efficient synthesis of modified 1,2,3-triazole nucleosides was developed. The strategy involved sequential one-pot acetylation-azidation-cycloaddition procedure and was found to be highly effective under a cooperative effect of ultrasound activation and iron/copper catalysis. The reactions were carried out under both conventional and ultrasonic irradiation conditions.

Microwave-assisted and efficient solvent-free knoevenagel condensation. A sustainable protocol using porous calcium hydroxyapatite as catalyst.

A sustainable Knoevenagel condensation of a series of aldehydes with malononitrile and ethyl cyanoacetate is described. The process is based on the combination of microwave activation and hydroxyapatite catalysis under solvent-free conditions. Products are obtained in and high yields after short reaction times.

1-(3-p-Tolyl-isoxazol-5-yl)cyclo-hexa-nol.

The title compound, C(16)H(19)NO(2), contains two mol-ecules in the asymmetric unit. Each mol-ecule is composed of three inter-connected rings, two essentially planar rings, viz. the isoxazole and the methyl-benzyl aromatic ring [maximum deviations of 0.

Efficient synthesis and in vitro cytostatic activity of 4-substituted triazolyl-nucleosides.

We report herein an efficient synthesis of 4-substituted triazolyl-nucleosides and their in vitro cytostatic activity. The synthesis is based on a straightforward 1,3-dipolar cycloaddition between 1-azido-ribose 2 and terminal alkynes under a cooperative effect of microwave activation and copper (I) catalysis. All cycloadducts were obtained in nearly quantitative yield after a short reaction time (1 to 2min).