Showing papers on "Piperidine published in 2022"

One-pot three-component synthesis of novel Phenyl-Pyrano-Thiazol-2-one derivatives and their anti-diabetic activity studies

Abstract: • A novel phenyl-pyrano-thiazol-2-one and its derivatives were synthesized by an efficient one-pot three-component reaction. • Phenyl-pyrano-thiazol-2-one derivatives gave good yields and characterized with spectroscopic methods. • These compounds exhibited excellent anti-diabetic activity against α ‐glucosidase. • The synthesized compounds act as a potent inhibitor in comparison with standard acarbose. An easy and rapid synthetic approach for the synthesis of phenyl-pyrano-thiazol-2-one derivatives using base catalysed one-pot three-component reaction between substituted aromatic aldehyde, N -methyl-1-(methylthio)-2-nitroethamine (NMSM) and thiazolidinedione is reported. Among the bases tested, piperidine was proven to be the most efficient organo-base catalyst, when ethanol was used as a solvent. The product was obtained in good yields and confirmed using FT-IR, NMR and mass spectroscopic techniques. The electron withdrawing group substituted product was obtained in higher yield compared to the electron donating group substituted product. The strategy used involved mild reaction conditions, shorter reaction time and easy isolation of products. The reaction sequence involved Knoevenagel condensation, Michael addition followed by intramolecular O -cyclization.

Stereoselective Palladium‐Catalyzed C( <i>sp</i> ³ )−H Mono‐Arylation of Piperidines and Tetrahydropyrans with a C(4) Directing Group

Abstract: A selective Pd-catalyzed C(3)−H cis-functionalization of piperidine and tetrahydropyran carboxylic acids is achieved using a C(4) aminoquinoline amide auxiliary. High mono- and cis-selectivity is attained by using mesityl carboxylic acid as an additive. Conditions are developed with significantly lower reaction temperatures (≤50 °C) than other reported heterocycle C(sp3)−H functionalization reactions, which is facilitated by a DoE optimization. A one-pot C−H functionalization-epimerization procedure provides the trans-3,4-disubstituted isomers directly. Divergent aminoquinoline removal is accomplished with the installation of carboxylic acid, alcohol, amide and nitrile functional groups. Overall, fragment compounds suitable for screening are generated in 3–4 steps from readily-available heterocyclic carboxylic acids.

Enhanced Dehydrogenative H2 Release from N-Containing Amphicyclic LOHC Boosted by Pd-Supported Nanosheet MFI Zeolites Having Strong Acidity and Large Mesoporosity

Abstract: The amount and rate of H2 discharge from 2-[(n-methylcyclohexyl)methyl]piperidine (H12-MBP), an amphicyclic liquid organic hydrogen carrier (LOHC) having two cycle moieties (cyclohexane and piperidine) with different reactivities, are determined by dehydrogenation of a cyclohexane ring with less reactivity. To realize high H2 yields with rapid kinetics, the cyclohexane ring in the partially dehydrogenated 2-[n-methylcyclohexyl]methyl)pyridine (H6-MBP) that is generated as the intermediate species should be fully dehydrogenated to 2-(n-methylbenzyl)pyridine (H0-MBP). This is approached using Pd-supported nanosheet zeolites having mesoporous structures bearing high concentrations of strongly acidic sites on external surfaces, which can not only enhance the diffusion of bulky H12-MBP but also strongly bind the basic piperidine ring in H12-MBP and H6-MBP. The H2 yields and rate constants are correlated with the acidity, mesoporosity, and adsorption behaviors of the LOHCs. As these factors are strengthened, H2 yield and rate constants increased dramatically within the ranges of 16.0–64.7% and 0.0001–0.0013 min–1, respectively. The results prove that mesoporous zeolites can be used for constructing supported Pd catalysts achieving high H2 yields with rapid kinetics from N-containing amphicyclic LOHCs.

Base-Free Synthesis and Photophysical Properties of New Schiff Bases Containing Indole Moiety

Abstract: Schiff bases represent an essential class in organic chemistry with antitumor, antiviral, antifungal, and antibacterial activities. The synthesis of Schiff bases requires the presence of an organic base as a catalyst such as piperidine. Base-free synthesis of organic compounds using a heterogeneous catalyst has recently attracted more interest due to the facile procedure, high yield, and reusability of the used catalyst. Herein, we present a comparative study to synthesize new Schiff bases containing indole moieties using piperidine as an organic base catalyst and Au@TiO2 as a heterogeneous catalyst. In both methods, the products were isolated in high yields and fully characterized using different spectral analysis techniques. The catalyst was reusable four times, and the activity was slightly decreased. The presence of Au increases the number of acidic sites of TiO2, resulting in C=O polarization. Yields of the prepared Schiff bases in the presence of Au@TiO2 and piperidine were comparable. However, Au@TiO2 is an easily separable and recyclable catalyst, which would facilitate the synthesis of organic compounds without applying any hazardous materials. Furthermore, the luminescence behavior of the synthesized Schiff bases exhibited spectral shape dependence on the substituent group. Interestingly, the compounds also displayed deep-blue fluorescence with Commission Internationale de l’Éclairage (CIE) coordinates of y < 0.1. Thus, these materials may contribute to decreasing the energy consumption of the emitting devices.

3-Chloro-3-methyl-2,6-diarylpiperidin-4-ones as Anti-Cancer Agents: Synthesis, Biological Evaluation, Molecular Docking, and In Silico ADMET Prediction

Abstract: Piperidine pharmacophore-containing compounds have demonstrated therapeutic efficacy against a range of diseases and are now being investigated in cancer. A series of 3-chloro-3-methyl-2,6-diarylpiperidin-4-ones, compounds (I–V) were designed and synthesized for their evaluation as a potential anti-cancer agent. Compounds II and IV reduced the growth of numerous hematological cancer cell lines while simultaneously increasing the mRNA expression of apoptosis-promoting genes, p53 and Bax. Molecular docking analyses confirmed that compounds can bind to 6FS1, 6FSO (myeloma), 6TJU (leukemia), 5N21, and 1OLL (NKTL). Computational ADMET research confirmed the essential physicochemical, pharmacokinetic, and drug-like characteristics of compounds (I–V). The results revealed that these compounds interact efficiently with active site residues and that compounds (II) and (V) can be further evaluated as potential therapeutic candidates.

Development of spiro-3-indolin-2-one containing compounds of antiproliferative and anti-SARS-CoV-2 properties

Abstract: A series of 1″-(alkylsulfonyl)-dispiro[indoline-3,2'-pyrrolidine-3',3″-piperidine]-2,4″-diones 6a‒o has been synthesized through regioselective multi-component azomethine dipolar cycloaddition reaction of 1-(alkylsulfonyl)-3,5-bis(ylidene)-piperidin-4-ones 3a‒h. X-ray diffraction studies (6b‒d,h) confirmed the structures. The majority of the synthesized analogs reveal promising antiproliferation properties against a variety of human cancer cell lines (MCF7, HCT116, A431 and PaCa2) with good selectivity index towards normal cell (RPE1). Some of the synthesized agents exhibit potent inhibitory properties against the tested cell lines with higher efficacies than the standard references (sunitinib and 5-fluorouracil). Compound 6m is the most potent. Multi-targeted inhibitory properties against EGFR and VEGFR-2 have been observed for the synthesized agents. Flow cytometry supports the antiproliferation properties and shows the tested agents as apoptosis and necrosis forming. Vero cell viral infection model demonstrates the anti-SARS-CoV-2 properties of the synthesized agents. Compound 6f is the most promising (about 3.3 and 4.8 times the potency of the standard references, chloroquine and hydroxychloroquine). QSAR models explain and support the observed biological properties.

Identification of Potential New Aedes aegypti Juvenile Hormone Inhibitors from N-Acyl Piperidine Derivatives: A Bioinformatics Approach

Abstract: Aedes aegypti mosquitoes transmit several human pathogens that cause millions of deaths worldwide, mainly in Latin America. The indiscriminate use of insecticides has resulted in the development of species resistance to some such compounds. Piperidine, a natural alkaloid isolated from Piper nigrum, has been used as a hit compound due to its larvicidal activity against Aedes aegypti. In the present study, piperidine derivatives were studied through in silico methods: pharmacophoric evaluation (PharmaGist), pharmacophoric virtual screening (Pharmit), ADME/Tox prediction (Preadmet/Derek 10.0®), docking calculations (AutoDock 4.2) and molecular dynamics (MD) simulation on GROMACS-5.1.4. MP-416 and MP-073 molecules exhibiting ΔG binding (MMPBSA −265.95 ± 1.32 kJ/mol and −124.412 ± 1.08 kJ/mol, respectively) and comparable to holo (ΔG binding = −216.21 ± 0.97) and pyriproxyfen (a well-known larvicidal, ΔG binding= −435.95 ± 2.06 kJ/mol). Considering future in vivo assays, we elaborated the theoretical synthetic route and made predictions of the synthetic accessibility (SA) (SwissADME), lipophilicity and water solubility (SwissADME) of the promising compounds identified in the present study. Our in silico results show that MP-416 and MP-073 molecules could be potent insecticides against the Aedes aegypti mosquitoes.

The Crystal Structure of 2-Amino-4-(2,3-Dichlorophenyl)-6-Methoxy-4H-Benzo[h]chromene-3-Carbonitrile: Antitumor and Tyrosine Kinase Receptor Inhibition Mechanism Studies

Abstract: The target compound, 2-amino-4-(2,3-dichlorophenyl)-6-methoxy-4H-benzo[h]chromene -3-carbonitrile (4), was synthesized via the reaction of 4-methoxynaphthalen-1-ol (1), 2,3-dichlorobenzaldehyde (2), and malononitrile (3) in an ethanolic piperidine solution under microwave irradiation. The synthesized β-enaminonitrile derivative (4) was characterized by spectral data and X-ray diffraction. The in vitro anti-proliferative profile was conducted against five cancer cell lines and was assessed for compound 4, which revealed strong and selective cytotoxic potency. This derivative showed promising inhibition efficacy against the EGFR and VEGFR-2 kinases in comparison to Sorafenib as a reference inhibitor. Lastly, the docking analysis into the EGFR and VEGFR-2 active sites was performed to clarify our biological findings.

Pyrido[1,2-e]purine: Design and Synthesis of Appropriate Inhibitory Candidates against the Main Protease of COVID-19

Abstract: A series of tricyclic and polycyclic pyrido[1,2-e]purine derivatives were designed and synthesized via a two-step, one-pot reaction of 2,4-dichloro-5-amino-6-methylpyrimidine with pyridine under reflux conditions. Various derivatives of pyrido[1,2-e]purine were also synthesized by substituting the chlorine atom with secondary amines. After careful physiochemical and pharmacokinetic predictions, the inhibitory effects of the synthesized compounds against the main protease of SARS-CoV-2 have been evaluated by molecular docking and molecular dynamics approaches. The in silico results revealed that among all of the studied compounds, the morpholine/piperidine-substituted pyrido[1,2-e]purine derivatives are the best candidates as effective inhibitors of SARS-CoV-2.

An Overview on the Synthesis of Fused Pyridocoumarins with Biological Interest

Abstract: Pyridocoumarins are a class of synthetic and naturally occurring organic compounds with interesting biological activities. This review focuses on the synthetic strategies for the synthesis of pyridocoumarins and presents the biological properties of those compounds. The synthesis involves the formation of the pyridine ring, at first, from a coumarin derivative, such as aminocoumarins, hydroxycoumarins, or other coumarins. The formation of a pyranone moiety follows from an existing pyridine or piperidine or phenol derivative. For the above syntheses, [4 + 2] cycloaddition reactions, multi-component reactions (MCR), as well as metal-catalyzed reactions, are useful. Pyridocoumarins present anti-cancer, anti-HIV, antimalarial, analgesic, antidiabetic, antibacterial, antifungal, anti-inflammatory, and antioxidant activities.

Development of spiro-3-indolin-2-one containing compounds of antiproliferative and anti-SARS-CoV-2 properties

Abstract: A series of 1″-(alkylsulfonyl)-dispiro[indoline-3,2'-pyrrolidine-3',3″-piperidine]-2,4″-diones 6a‒o has been synthesized through regioselective multi-component azomethine dipolar cycloaddition reaction of 1-(alkylsulfonyl)-3,5-bis(ylidene)-piperidin-4-ones 3a‒h. X-ray diffraction studies (6b‒d,h) confirmed the structures. The majority of the synthesized analogs reveal promising antiproliferation properties against a variety of human cancer cell lines (MCF7, HCT116, A431 and PaCa2) with good selectivity index towards normal cell (RPE1). Some of the synthesized agents exhibit potent inhibitory properties against the tested cell lines with higher efficacies than the standard references (sunitinib and 5-fluorouracil). Compound 6m is the most potent. Multi-targeted inhibitory properties against EGFR and VEGFR-2 have been observed for the synthesized agents. Flow cytometry supports the antiproliferation properties and shows the tested agents as apoptosis and necrosis forming. Vero cell viral infection model demonstrates the anti-SARS-CoV-2 properties of the synthesized agents. Compound 6f is the most promising (about 3.3 and 4.8 times the potency of the standard references, chloroquine and hydroxychloroquine). QSAR models explain and support the observed biological properties.

Synthesis and Solvent Dependent Fluorescence of Some Piperidine-Substituted Naphthalimide Derivatives and Consequences for Water Sensing

Abstract: Novel fluorescent strigolactone derivatives that contain the piperidine-substituted 1,8-naphthalimide ring system connected through an ether link to a bioactive 3-methyl-furan-2-one unit were synthesized and their spectroscopic properties investigated. The solvatochromic behavior of these piperidine-naphthalimides was monitored in solvents of different polarity using the electronic absorption and fluorescence spectra. These compounds exhibited a strong positive solvatochromism taking into account the change of solvent polarity, and the response mechanism was analyzed by fluorescence lifetime measurements. According to Catalan and [f(n), f(ε), β, α] solvent scales, the dipolarity and polarizability are relevant to describe the solute–solvent interactions. The emission chemosensing activity was discussed in order to determine the water content in organic environments. The emission intensity of these compounds decreased rapidly in dioxane, increasing water level up to 10%. Measuring of quantum yield indicated that the highest values of quantum efficiency were obtained in nonpolar solvents, while in polar solvents these derivatives revealed the lowest quantum yield. The fluorescence decay can be described by a monoexponential model for low water levels, and for higher water contents a biexponential model was valid.

Organocatalyst-mediated five-pot synthesis of (–)-quinine

Abstract: Abstract In this work, the enantioselective total synthesis of (–)-quinine has been accomplished in a pot-economical manner using five reaction vessels. In the first pot, reactions involve the diphenylprolinol silyl ether-mediated Michael reaction, aza-Henry reaction, hemiaminalization, and elimination of HNO 2 (five reactions), affording a chiral tetrahydropyridine with excellent enantioselectivity. In the second pot, five reactions proceed with excellent diastereoselectivity to afford a trisubstituted piperidine with the desired stereochemistry. A further five reactions are carried out in the last one-pot sequence.

Development of Yellow-to-Orange Photoluminescence Molecules Based on Alterations in the Donor Units of Fluorinated Tolanes

Abstract: Since the aggregation-induced emission (AIE) phenomenon was first reported by Tang et al., much effort has been devoted to the development of solid-state luminescent molecules by chemists worldwide. Our group successfully developed fluorinated tolanes as novel compact π-conjugated luminophores with blue photoluminescence (PL) in the crystalline state. Moreover, we reported the yellow-green PL molecules based on their electron-density distributions. In the present study, we designed and synthesized fluorinated tolanes with various amine-based donors and evaluated their photophysical properties. The carbazole-substituted fluorinated tolane exhibited strong PL in the solution state, whereas piperidine- or phenothiazine-substituted fluorinated tolanes showed a dramatic decrease in PL efficiency. Notably, fluorinated tolanes with piperidine or phenothiazine substituents displayed yellow-to-orange PL in the crystalline state; this may have occurred because these tolanes exhibited tightly packed structures formed by intermolecular interactions, such as H···F hydrogen bonds, which suppressed the non-radiative deactivation process. Moreover, fluorinated tolanes with amine-based donors exhibited AIE characteristics. We believe that these yellow-to-orange solid PL molecules can contribute to the development of new solid luminescent materials.