Search Results (58)

Reductive deuteration of N-heterocycles provides an efficient route to deuterated scaffolds, yet achieving controlled deuterium incorporation in quinoline remains challenging. Herein, we report a high-temperature H₂-treated Rh/TiO₂ catalyst (Rh/TiO₂–H500) that enables efficient reductive deuteration of quinoline using D₂O as a deuterium source. Structural characterization reveals that reduction at 500 °C induces a pronounced strong metal–support interaction (SMSI), leading to partial TiO_x encapsulation of Rh nanoparticles and interfacial electron transfer that generates electron-rich Rh⁰ species. This optimized interfacial structure promotes cooperative C–H activation and effective H/D transfer across the reduced quinoline framework, affording high deuterium incorporation at multiple positions of 1,2,3,4-tetrahydroquinoline (THQ). These results highlight the importance of SMSI-driven electronic and interfacial modulation in regulating reductive H/D exchange over heterogeneous catalysts. Full article

This study aimed to develop new catalysts, based on MoS₂, for the hydrogenation of bromoquinolines without C-Br bond cleavage. The mechanochemical exfoliation of the bulk MoS₂ in the presence of NaCl resulted in the formation of the material (MoS₂-1), consisting of flat plates of size between ca. 40 × 100 and ca. 250 × 400 nm². Similar grinding of MoS₂ in the presence of NH₄Cl produced smaller nanoplates of size between ca. 10 × 30 and ca. 50 × 300 nm² (MoS₂-2). These materials were characterized using powder XRD, TEM, SEM, Raman spectroscopy and XPS. The specific surface area of the MoS₂-1 and MoS₂-2 samples was estimated using the analysis of N₂ adsorption isotherms. Both materials were catalytically active in the hydrogenation of quinoline; 1,2,3,4-tetrahydroquinoline (THQ) was the sole product and its yield grew proportionally to the accessible surface area of the catalyst. The hydrogenation of 5- and 8-bromoquinolines in the presence of MoS₂-1 and MoS₂-2 led to the respective bromo-THQs with almost quantitative yields, while the hydrogenation of 6-bromoquinoline resulted in the formation of the respective 6-bromo-THQ with the yield up to 30%. In the case of 7-bromoquinoline, N-methylated 7-bromo-THQ was formed almost quantitatively. Full article

3,4-dihydroquinolone and its derivatives are structural motifs found in diverse pharmacologically active compounds. Direct oxidation of tetrahydroquinolines represents the most efficient synthetic route to 3,4-dihydroquinolone. However, the reaction conditions reported in previous studies were either relatively harsh or complex. We also attempted previously reported photocatalytic oxidation methods for the α-carbonylation of amines, but these approaches failed to efficiently produce 3,4-dihydroquinolone. Herein, we present an efficient photocatalytic oxidation methodology facilitated by our in-house high-throughput microfluidic system, which can be carried out under mild conditions with a short reaction time. Moreover, a new reaction mechanism, in which the organic base DBU serves a dual role as both an electron donor and a hydrogen atom transfer (HAT) mediator, is proposed and supported by DFT calculations. Full article

This research focuses on synthesizing novel tetrahydroquinoline–1,2,3-triazole hybrids as potential agents for neurodegenerative diseases, particularly Alzheimer’s disease (AD). The series of structurally distinct hybrid compounds synthesized in this study has not been previously reported in the literature. The synthetic strategy involved a diastereoselective imino Diels–Alder reaction (Povarov reaction) to construct the tetrahydroquinoline (THQ) core, where various catalysts, including phthalic acid, Lewis acids, KSF (montmorillonite), and ceric ammonium nitrate (CAN), were screened. Phthalic acid was selected as the most efficient catalyst for this crucial step. Following this, we employed efficient click chemistry to introduce the triazole moiety, adhering to green chemistry principles throughout the process. The chemical structure of the synthetized compounds was assigned using an analysis of Nuclear Magnetic Resonance (NMR), Mass Spectrometry (MS), and Infrared (IR) spectroscopy. Furthermore, in silico analyses performed with Swiss ADME and OSIRIS Property Explorer indicated that most compounds exhibited excellent drug-like characteristics and favorable pharmacokinetic profiles. The synthesized compounds were evaluated as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) using the modified Ellman methodology. The inhibitory activity is presented as IC₅₀ values for each enzyme and compared to galantamine as a reference standard. These findings offer promising directions for the development of new therapeutic agents for AD based on organic synthesis. Full article

Nickel phosphide catalysts (Ni₂P) were prepared using mesoporous molecular sieves as supports during isobaric co-impregnation. Ni₂P catalysts with different loading values were characterized, showing that the active phase on the surface of the catalysts was mainly Ni₂P and the catalysts still retained the mesoporous structural characteristics of the supports. The catalysts were evaluated using a 10 mL fixed-bed hydrogenation unit. The results showed that the nickel phosphide catalysts had a higher hydrogenation capacity than the sulfide catalysts and were able to preferentially hydrogenate and saturate most of the quinolines to decahydroquinolines, reduce the conversion of 1,2,3,4-tetrahydroquinoline to o-propylaniline, and reduce the inhibition of reactivity due to competitive adsorption. The effect of the catalyst on the path selectivity of quinoline hydrogenation was investigated, and the products of quinoline hydrogenation and denitrogenation consisted mainly of propylbenzene and propylcyclohexane, with propylcyclohexane accounting for 91.7% of the product and propylbenzene for 4.8%, under the conditions of nickel phosphide catalysts. Furthermore, the 25 wt% Ni₂P/SBA-15 catalyst exhibited no significant loss of catalytic activity during a 72 h stability evaluation conducted at 360 °C. Full article

Multicomponent reactions (MCRs) enable the efficient assembly of complex small molecules via multiple bond-forming events in a single step. However, individual MCRs typically yield products with similar core structures, limiting access to larger, more intricate scaffolds. Strategic selection of reactants allows the combination of distinct MCRs, thus facilitating the synthesis of advanced molecular architectures with potential biological significance. Using our previously reported method for performing the aza-Friedel Crafts multicomponent reaction under green heterogeneous conditions, we have incorporated some of the obtained products into diverse multicomponent reactions to generate, in an unprecedent approach, eight novel products, some of which were also characterized by two-dimensional NMR techniques. The biological properties of such products are under investigation. Full article

Backgrounds: This study explores the design of substituted tetrahydroquinoline (THQ) derivatives and their synthesis as possible inhibitors of mTOR inhibitors for targeted cancer therapy. Methods: Inspired by the structural characteristics of known mTOR inhibitors, eight novel derivatives were synthesized, characterized using mass spectroscopy, ¹H, and ¹³C NMR, and evaluated for anticancer activity. Results: Computational studies, including molecular docking and molecular dynamics (MD) simulations, highlighted the derivative’s strong binding interaction and stability within the mTOR active site. Assays for in vitro cytotoxicity showed strong and specific anticancer action against cell lines of triple-negative breast cancer, lung cancer, and breast cancer while causing negligible impact on healthy cells. Conclusions: Compound 10e emerged as the most promising candidate, displaying exceptional activity against A549 cells (IC₅₀ = 0.033 µM) and inducing apoptosis in a dose-dependent manner, surpassing standard agents, like Everolimus and 5-flurouracil. Structure–activity relationship analysis revealed that incorporating trifluoromethyl and morpholine moieties significantly enhanced selectivity and potency. MD simulations further validated these findings, confirming stable protein-ligand interactions and favorable dynamics over a 100-ns simulation period. Collectively, this study underscores the therapeutic potential of THQ derivatives, particularly compound 10e, as promising mTOR inhibitors with potential applications in lung cancer treatment. Full article

Within the area of study of neurodegenerative diseases, particularly Alzheimer’s disease (AD), this research focused on the synthesis and evaluation of novel tetrahydroquinoline (THQ) derivatives with potential antioxidant activity. The toluidine N-propargylation synthesis protocol was optimized, achieving a significant increase in yield by using sodium carbonate and reaction temperature variation. Subsequently, four THQ compounds with alkene variation were successfully synthesized, including some which had not been previously reported in the literature. The synthesized compounds were characterized by nuclear magnetic resonance (NMR), mass spectrometry, and infrared spectroscopy (IR), which confirmed their structures and purity. In silico analyses performed with SwissADME and OSIRIS Property Explorer indicated that most of the compounds exhibited excellent drug-like characteristics and favorable pharmacokinetic profiles. Antioxidant evaluation was performed using DPPH and ABTS assays, in which all compounds demonstrated excellent antioxidant capacity, with EC50 values below 10 μg/mL in the ABTS assay, significantly outperforming the ascorbic acid control (EC50 = 35 μg/mL). The results suggest that the predominant radical-scavenging mechanism is single electron transfer (SET). This study provides a solid foundation for further investigations into the potential of THQs’ derivatives as antioxidants, and potential cholinesterase inhibitors in the context of neurodegenerative diseases such as Alzheimer’s. As a future projection, an enzymatic evaluation, including regarding mechanisms of action and the exploration of a hybrid synthesis of THQ/triazole, is proposed based on these promising results. Full article

Tetrahydroquinolines are key structures in a variety of natural products with diverse pharmacological utilities and other applications. A series of 3,4-diaryl-5,7-dimethoxy-1,2,3,4-tetrahydroquinolines were synthesized in good yield by reacting 3-aryl-5,7-dimethoxy-2,3-dihydroquinolin-4-ones with different Grignard reagents followed by the dehydration of the intermediate phenolic compounds. Subsequent reduction and deprotection were carried out to achieve the desired tetrahydroquinolone moiety. The lead compound 3c showed low micromolar inhibition of various cancer cell lines. Demethylation under different reaction conditions was also investigated to afford the corresponding monohydroxy analogues. Full article

A set of Pd-containing composites was prepared by the deposition of Pd on the following carriers: polyaniline (PANI); PANI doped by H₂SO₄; Norit GSX activated carbon or Aerosil (SiO₂) coated by PANI or by H₂SO₄-doped PANI; PANI after thermal treatment at 300 °C in an atmosphere of H₂. One sample was also prepared by the in situ polymerization of aniline in the presence of Pd²⁺· The decomposition of Pd was carried out via deposition from the solutions of Pd²⁺ salts or decomposition of Pd⁰ complex Pd₂(dba)₃, where dba is dibenzylideneacetone. The composites were studied by powder X-ray diffraction, transmission electron microscopy, IR and Raman spectroscopy. The hydrogenation of quinoline in the presence of composites was carried out; the catalytic performance of the composites was evaluated by the yield of 1,2,3,4-tetrahydroquinoline. It was found that the doping of PANI by H₂SO₄, inclusion of Norit GSX activated carbon as a component of the carrier or thermal treatment of PANI prior to the deposition of Pd led to significant increase in the catalytic performance of the composites in the hydrogenation of quinoline. Full article

The efficient hydrogenation of N-heterocycles with H₂ under mild conditions remains a significant challenge. In this work, polyphosphazene (PZs) microspheres, novel organic–inorganic hybrid materials possessing unique –P=N– structural units and a diverse range of side groups, were used to serve as support for the design of a stable and efficient Pd nanocatalyst (Pd/PZs). The PZs microspheres were prepared by self-assembly induced by precipitation polymerization, and Pd nanoparticles were grown and loaded on the support by a chemical reduction process. Several characterization techniques, including XRD, FTIR, SEM, TEM, XPS, BET and TGA, were used to study the structural features of the nanocomposites. The results revealed that Pd nanoparticles were uniformly distributed on the PZs microspheres, with primary sizes ranging from 4 to 9 nm based on the abundance of functional P/N/O groups in PZs. Remarkably high catalytic activity and stability were observed for the hydrogenation of quinoline compounds using the Pd/PZs nanocatalyst under mild conditions. Rates of 98.9% quinoline conversion and 98.5% 1,2,3,4-tetrahydroquinoline selectivity could be achieved at a low H₂ pressure (1.5 bar) and temperature (40 °C). A possible reaction mechanism for quinoline hydrogenation over Pd/PZs was proposed. This work presents an innovative approach utilizing a Pd-based nanocatalyst for highly efficient multifunctional hydrogenation. Full article

A study was conducted to investigate the effects of different doses of 6-hydroxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (HTHQ) on motor coordination scores, brain tissue morphology, the expression of tyrosine hydroxylase, the severity of oxidative stress parameters, the levels of the p65 subunit of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) factor, and the inflammatory response in rats during the development of rotenone-induced Parkinsonism. The findings indicate that HTHQ, with its antioxidant attributes, reduced the levels of 8-isoprostane, lipid oxidation products, and protein oxidation products. The decrease in oxidative stress due to HTHQ led to a reduction in the mRNA content of proinflammatory cytokines and myeloperoxidase activity, accompanying the drop in the expression of the factor NF-κB. These alterations promoted an improvement in motor coordination scores and increased tyrosine hydroxylase levels, whereas histopathological changes in the brain tissue of the experimental animals were attenuated. HTHQ exhibited greater effectiveness than the comparative drug rasagiline based on the majority of variables. Full article

Herein, we report the synthesis of four new hybrid molecules between ketoprofen or 2-(3-benzoylphenyl)propanoic acid and N-containing heterocyclic compounds, such as piperidine, pyrrolidine, 1,2,3,4-tetrahydroquinoline, and 1,2,3,4-tetrahydroisoquinoline. The obtained hybrid compounds were fully characterized using ¹H- and ¹³C-NMR, UV-Vis, and HRMS spectra. Detailed HRMS analysis is provided for all novel hybrid molecules. The compounds were assessed for their in vitro anti-inflammatory and antioxidant activity. The lipophilicity of the hybrids was determined, both theoretically (cLogP) and experimentally (R_M). The affinity of the compounds to the human serum albumin was assessed in silico by molecular docking study using two software, and the stability of the predicted complexes was evaluated by molecular dynamics study. All novel hybrids have shown very good HPSA activity, statistically close when compared to the reference—quercetin. The molecular docking confirmed the obtained in vitro results. Tetrahydroquinoline derivative 3c and tetrahydroisoquinoline derivative 3d have the highest affinity for albumin. They show stronger anti-inflammatory action than their predecessor, ketoprofen and the regularly used ibuprofen. Full article

Despite extensive research in the field of thrombotic diseases, the prevention of blood clots remains an important area of study. Therefore, the development of new anticoagulant drugs with better therapeutic profiles and fewer side effects to combat thrombus formation is still needed. Herein, we report the synthesis and evaluation of novel pyrroloquinolinedione-based rhodanine derivatives, which were chosen from 24 developed derivatives by docking as potential molecules to inhibit the clotting factors Xa and XIa. For the synthesis of new hybrid derivatives of pyrrolo[3,2,1-ij]quinoline-2-one, we used a convenient structural modification of the tetrahydroquinoline fragment by varying the substituents in positions 2, 4, and 6. In addition, the design of target molecules was achieved by alkylating the amino group of the rhodanine fragment with propargyl bromide or by replacing the rhodanine fragment with 2-thioxoimidazolidin-4-one. The in vitro testing showed that eight derivatives are capable of inhibiting both coagulation factors, two compounds are selective inhibitors of factor Xa, and two compounds are selective inhibitors of factor XIa. Overall, these data indicate the potential anticoagulant activity of these molecules through the inhibition of the coagulation factors Xa and XIa. Full article

Chiral diamines based on an 8-amino-5,6,7,8-tetrahydroquinoline backbone, known as CAMPY (L1), or the 2-methyl substituted analogue Me-CAMPY (L2) were employed as novel ligands in Cp* metal complexes for the ATH of a series of substituted dihydroisoquinolines (DHIQs), known for being key intermediates in the synthesis of biologically active alkaloids. Different metal-based complexes were evaluated in this kind of reaction, rhodium catalysts, C3 and C4, proving most effective both in terms of reactivity and enantioselectivity. Although modest enantiomeric excess values were obtained (up to 69% ee in the case of substrate I), a satisfactory quantitative conversion was successfully fulfilled even in the case of the most demanding hindered substrates when La(OTf)₃ was used as beneficial additive, opening up the possibility for a rational design of novel chiral catalysts alternatives to the Noyori-Ikariya (arene)Ru(II)/TsDPEN catalyst. Full article