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Piperidine derivatives are highly abundant in natural products and pharmaceutically relevant compounds. Aza‐Prins cyclization has emerged as a step‐ atom‐economical and stereoselective method for the preparation of such azacycles. The possibility of coupling aza‐Prins process with the formation of a second cycle in a one‐pot manner is even more powerful and makes the object of this review. Cascade/domino/tandem bis‐cyclizations involving an aza‐Prins process, for the rapid construction of complex small molecules, are discussed in detail. [ABSTRACT FROM AUTHOR]

Objective: USP14 (Ubiquitin‐specific‐processing protease 14) is a deubiquitinating enzyme with oncogenic effects in oral squamous cell carcinoma (OSCC). This study aims to identify new substrates of USP14 and elucidate their role in modulating cancer stem‐like cells (CSCs) in OSCC. Materials and Methods: Bioinformatics prediction and docking were performed using UbiBrowser 2.0 and HDOCK, respectively. OSCC cell lines and patient‐derived cells were used for experimental validation, employing co‐immunoprecipitation, cycloheximide chase assays, and tumor sphere formation to evaluate the effects of USP14 on SOX2 stability, ubiquitination, and CSC phenotypes. Results: USP14 upregulation was associated with worse overall survival and progression‐free interval in OSCC. USP14 interacted with SOX2 with its ubiquitin carboxyl‐terminal hydrolase domain. USP14 knockdown impaired SOX2 stability by increasing its polyubiquitination. Ectopic overexpression of wild‐type USP14, but not the hydrolase‐deficient‐mutant USP14C114A, enhanced SOX2 stability by reducing polyubiquitination. USP14 knockdown suppressed OSCC cell proliferation, colony formation, and tumor sphere formation in vitro and tumor growth in vivo. However, the reduction of CSC markers following USP14 knockdown was mitigated by overexpressing SOX2. These findings were verified in OSCC patient‐derived CSC cells. Conclusion: This study revealed a USP14‐SOX2 axis regulating the CSC properties of OSCC. [ABSTRACT FROM AUTHOR]

Dihydrofolate reductase (DHFR), an essential enzyme in folate metabolism, presents a promising target for drug development against various diseases, including cancer and tuberculosis. Herein, we present an integrated approach combining in vitro biochemical assays with in silico molecular docking analysis to evaluate the inhibitory potential of 4-piperidine-based thiosemicarbazones 5(a-s) against DHFR. In our in vitro study, a novel series of 4-piperidine-based thiosemicarbazones 5(a-s) were assessed for their inhibitory activity against DHFR enzyme. The synthesized compounds 5(a-s) exhibited potent inhibition with IC50 values in the range of 13.70 ± 0.25 µM to 47.30 ± 0.86 µM. Among all the derivatives 5p displayed highest inhibitory activity. Simultaneously, in silico analysis were performed and compared with standard drug (Methotrexate) to predict the binding affinity and interaction pattern of synthesized compounds with DHFR active site. SAR analysis was done to elucidate how structural modifications impact compound’s biological activity, guiding the rational design of potent and selective drug candidates for targeted diseases. These findings may provide a comprehensive assessment of 4-piperdine-based thiosemicarbazones as DHFR inhibitors and contribute to the development of novel therapeutics targeting DHFR-associated diseases. [ABSTRACT FROM AUTHOR]

Acute leukemia is characterized by abnormal white blood cell proliferation with rapid onset and severe complications. Natural compounds, which are alternative treatments, are widely used in cancer treatment. Piperine, an alkaloid compound from black pepper, exerts anticancer effects through the cell death signaling pathway. Autophagy and senescence signaling pathways are considered target signaling pathways for cancer treatment. In this study, we investigated the effects of piperine via autophagy and senescence signaling pathways in NB4 and MOLT-4 cells. The MTT assay results demonstrated that piperine significantly decreased the viability of NB4 and MOLT-4 cells. Piperine induced autophagy by increasing LC3, Beclin-1 and ULK1 and decreasing mTOR and NF-κB1 expression in NB4 and MOLT-4 cells. In addition, piperine increased senescence-associated beta-galactosidase fluorescence intensity by increasing p21 and IL-6 expression while decreasing CDK2 expression in NB4 and MOLT-4 cells. In conclusion, our study provides additional information about the induction of autophagy and senescence by piperine in acute leukemia. [ABSTRACT FROM AUTHOR]

Piperidines are widely present in small molecule drugs and natural products. Despite many methods have been developed for their synthesis, new approaches to polysubstituted piperidines are highly desirable. This work presents a radical (4+2) cycloaddition reaction for synthesis of piperidines featuring dense substituents at 3,4,5‐positions that are not readily accessible by known methods. Using commercially available diboron(4) compounds and 4‐phenylpyridine as the catalyst precursors, the boronyl radical‐catalyzed cycloaddition between 3‐aroyl azetidines and various alkenes, including previously unreactive 1,2‐di‐, tri‐, and tetrasubstituted alkenes, has delivered the polysubstituted piperidines in generally high yield and diastereoselectivity. The reaction also features high modularity, atom economy, broad substrate scope, metal‐free conditions, simple catalysts and operation. The utilization of the products has been demonstrated by selective transformations. A plausible mechanism, with the ring‐opening of azetidine as the rate‐limiting step, has been proposed based on the experimental and computational results. [ABSTRACT FROM AUTHOR]

Background: Although the Lee Silverman Voice Treatment BIG® (LSVT BIG®) improves motor symptoms in patients with Parkinson's Disease, no reports exist for patients with Progressive Supranuclear Palsy (PSP). Objective: To describe the effect of LSVT BIG® on the motor symptoms of a participant with PSP. Case Description: The participant was a 74-year-old man with PSP. His goals were to improve limb movement, balance ability, and festinating gait over the 4-week LSVT BIG® program. Outcomes: All assessments of limb movement and balance ability showed improvements after intervention for the limb and gait subsections of the PSP rating scale. Scores improved from 9 to 5, and 8 to 6, respectively for the Unified Parkinson's Disease Rating Scale (UPDRS) Part 3, from 30 to 21 and for the Berg balance scale (BBS), from 45 to 50 points. The improvements in UPDRS Part 3 and BBS exceeded the minimum detectable change values (7–8 and 2 points, respectively). After intervention, improvements in festinating gait and rapid walking pace were noted on the UPDRS Part 3 (2 to 1 point) and 10-meter walk test (1.65 m/s to 1.10 m/s). Conclusion: The intervention was effective for the participant but further studies with diverse populations are needed. [ABSTRACT FROM AUTHOR]

The collection, storage, and transport of samples prior to and during analysis is of utmost importance, especially for highly potent analogs that may not be present in high concentrations and are susceptible to pH or thermally mediated degradation. An accelerated stability study was performed on 17 fentanyl analogs (fentalogs) over a wide range of pH (2–10) and temperature (20–60°C) conditions over 24 h. Dilute aqueous systems were used to investigate temperature and pH‐dependent kinetics using liquid chromatography–tandem mass spectrometry (LC–MS/MS). Liquid chromatography‐quadrupole/time‐of‐flight‐mass spectrometry (LC‐Q/TOF–MS) was used for structural elucidation of degradants. With the exception of remifentanil, all fentalogs evaluated were stable at pH 6 or lower. Fentalogs were generally unstable in strongly alkaline environments and at elevated temperatures. Remifentanil was the least stable drug and N‐dealkylated fentalogs were the most stable. Fentanyl degraded to acetylfentanyl, norfentanyl, fentanyl N‐oxide, and 1‐phenethylpyridinium salt (1‐PEP). A total of 26 unique breakdown products were observed for 15 of the fentanyl derivatives studied. Common degradation pathways involved N‐dealkylation, oxidation of the piperidine nitrogen, and β‐elimination of N‐phenylpropanamide followed by oxidation/dehydration of the piperidine ring. Ester and amide hydrolysis, demethylation at the propanamide, and O‐demethylation were observed for selected fentalogs only. The potential for analyte loss should be considered during the pre‐analytical phase (i.e., shipping and transport) where environmental conditions may not be controlled, as well as during the analysis itself. [ABSTRACT FROM AUTHOR]

Objective: Following recent changes to the German Narcotics Act, this article examines prehospital analgesia by paramedics using piritramide vs. nalbuphine + paracetamol. Material and methods: Prehospital analgesia administered by paramedics from the Fulda (piritramide) and Gütersloh (nalbuphine + paracetamol) emergency services was compared regarding pain intensity at the beginning and end of the mission, measured using the numeric rating scale (NRS). Additionally, an analysis of the resulting complications was carried out. Results: In this study 2429 administrations of analgesia were evaluated (nalbuphine + paracetamol: 1635, 67.3%, initial NRS: 8.0 ± 1.4, end of NRS: 3.7 ± 2.0; piritramide: 794, 32.7%, initial NRS: 8.5 ± 1.1, end of NRS: 4.5 ± 1.6). Factors influencing NRS change were initial NRS (regression coefficient, RC: 0.7075, 95% confidence interval, CI: 0.6503–0.7647, p < 0.001), treatment with nalbuphine + paracetamol (RC: 0.6048, 95% CI: 0.4396–0.7700, p < 0.001). Treatment with nalbuphine + paracetamol (n = 796 (48.7%)) compared to piritramide (n = 190 (23.9%)) increased the odds of achieving NRS < 4 (odds ratio, OR: 2.712, 95% CI: 2.227–3.303, p < 0.001). Complications occurred in n = 44 (5.5%) with piritramide and in n = 35 (2.1%) with nalbuphine + paracetamol. Risk factors for complications were analgesia with piritramide (OR: 2.699, 95% CI: 1.693–4.301, p < 0.001), female sex (OR: 2.372, 95% CI: 1.396–4.029, p = 0.0014), and age (OR: 1.013, 95% CI: 1.002–1.025, p = 0.0232). Conclusion: Compared with piritramide, prehospital analgesia with nalbuphine + paracetamol has favorable effects in terms of analgesic efficacy and complication rates and should therefore be considered in future recommendations for paramedics. [ABSTRACT FROM AUTHOR]

An experimental and computational study (including DFT calculations and distortion/interaction analysis) was conducted to assess the effect of the nitrone structure in the outcome of dipolar 1,3‐cycloadditions with levoglucosenone, a biomass derived chiral enone. While B3LYP/6‐31G* (the most popular method for modeling these reactions according to our literature search) provides qualitatively good results, large outliers were found for some systems versus experimental data. An exhaustive exploration of other levels allowed us to determine the most appropriate ones to predict simultaneously reactivity and selectivity. The systematically predicted high exo selectivity by the majority of the levels led us to reconsider our initial assignment for the reaction with the nitrone derived from piperidine, which resulted in the discovery of an interesting case of conformational dynamics. [ABSTRACT FROM AUTHOR]

Aripiprazole is an atypical antipsychotic medication indicated for the treatment of schizophrenia and bipolar disorders. The drug has been shown to exhibit acceptable efficacy and is often preferred as a first‐line psychiatric treatment option owing to its lower incidence of adverse effects. While first‐generation antipsychotics are associated with extrapyramidal syndrome (EPS), atypical antipsychotics such as aripiprazole are generally associated with a lower frequency of EPS. In this case, we present a 31‐year‐old woman with a history of bipolar disorder who developed EPS after ingesting 200 mg of aripiprazole. Fortunately, her symptoms improved with the administration of biperiden, and she was discharged five days after ingestion. This case highlights the potential for significant consequences associated with aripiprazole, even within its therapeutic index. [ABSTRACT FROM AUTHOR]

Simple Summary: NSCLC is one of the most life-threatening forms of oncological diseases. Although targeted and immunotherapy treatments have improved NSCLC prognosis, the chance of surviving is still limited for many patients. Therefore, further efforts are required to improve NSCLC care. AdipoRon is emerging as an antineoplastic molecule in the treatment of different cancers, but its potential in NSCLC is yet to be explored. Herein, we demonstrated that AdipoRon strongly impairs viability, growth and stemness in NSCLC cells. We also recorded higher glucose consumption and lactate accumulation as a result of AdipoRon treatment. Remarkably, the employment of glycolytic-interfering agents enhanced its antiproliferative features. A signaling pathways analysis revealed a marked AMPK phosphorylation, while, in contrast, its abrogation by Compound-C significantly counteracted AdipoRon effectiveness. Altogether, these findings emphasize AdipoRon's anticancer feature even in NSCLC, supporting its endorsement as a future candidate in cancer and NSCLC therapy. Despite the countless therapeutic advances achieved over the years, non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. To this primacy contribute both non-oncogene addicted and advanced NSCLCs, in which conventional therapies are only partially effective. The adiponectin receptor agonist AdipoRon has revealed antiproliferative action in different cancers, including osteosarcoma and pancreatic cancer. Herein, we investigated its potential anticancer role in NSCLC for the first time. We proved that AdipoRon strongly inhibits viability, growth and colony formation in H1299 and A549 NSCLC cells, mainly through a slowdown in cell cycle progression. Along with the biological behaviors, a metabolic switching was observed after AdipoRon administration in NSCLC cells, consisting of higher glucose consumption and lactate accumulation. Remarkably, both 2-Deoxy Glucose and Oxamate glycolytic-interfering agents greatly enhanced AdipoRon's antiproliferative features. As a master regulator of cell metabolism, AMP-activated protein kinase (AMPK) was activated by AdipoRon. Notably, the ablation of AdipoRon-induced AMPK phosphorylation by Compound-C significantly counteracted its effectiveness. However, the engagement of other pathways should be investigated afterwards. With a focus on NSCLC, our findings further support the ability of AdipoRon in acting as an anticancer molecule, driving its endorsement as a future candidate in NSCLC therapy. [ABSTRACT FROM AUTHOR]

Objectives: Perennial allergic rhinitis (PAR) is common in Japan. Second-generation antihistamines (SGAs) are commonly used for its treatment; however, it remains unclear which SGA is the most cost-effective. Additionally, the pharmacoeconomics of Japanese Kampo shoseiryuto (which was traditionally prescribed to treat PAR in Japan) remains poorly understood. In this study, we aimed to investigate the effectiveness of various SGAs and shoseiryuto for the treatment of PAR in Japanese outpatients, from the healthcare payer's perspective. Methods: The most cost- and clinically effective SGAs were determined from a list of 6 SGAs (bepotastine, 10 mg; cetirizine, 10 mg; ebastine, 10 mg; epinastine, 20 mg; loratadine, 10 mg; and olopatadine, 5 mg) together with shoseiryuto, using the overall improvement rate through a model-based analysis. The time horizon was 28 days. Costs were determined based on the Medical Fee Index in 2020. Deterministic and probabilistic sensitivity analyses were conducted to address the uncertainty of the base-case results. Results: Overall, bepotastine (10 mg) and ebastine (10 mg) were cost-effective. Shoseiryuto was less cost-effective than ebastine (10 mg) (dominated). Ebastine (10 mg) was the most cost-effective option based on deterministic and probabilistic sensitivity analyses. Conclusions: Ebastine (10 mg) was the most cost-effective treatment strategy for PAR among the agents evaluated in this study. This insight could aid in establishing an appropriate formulary for treating PAR in hospitals and communities. [ABSTRACT FROM AUTHOR]

Stoma patients require continuous support throughout their entire journey with a stoma. Although many Stoma Care Services across the UK offer patient follow-up pathways, there is not one unified pathway. Patients may not be prepared for life with a stoma because, depending on their stoma type, they will have specific needs, and if patients and healthcare professionals are not prepared to manage these stoma-specific needs, complications and hospital readmissions may occur, worsening patients' outcomes and quality of life. Ileostomy patients are known to be more likely to experience complications, including hospital readmissions, and therefore, special care should be taken when preparing these patients for life with a stoma. They should be informed and educated to prevent complications, and if this is not always possible, thye should at least be able to recognise and manage early signs and symptoms of complications. This will empower them to self-care and know when to seek medical attention. [ABSTRACT FROM AUTHOR]

Abstract Dihydrofolate reductase (DHFR), an essential enzyme in folate metabolism, presents a promising target for drug development against various diseases, including cancer and tuberculosis. Herein, we present an integrated approach combining in vitro biochemical assays with in silico molecular docking analysis to evaluate the inhibitory potential of 4-piperidine-based thiosemicarbazones 5(a-s) against DHFR. In our in vitro study, a novel series of 4-piperidine-based thiosemicarbazones 5(a-s) were assessed for their inhibitory activity against DHFR enzyme. The synthesized compounds 5(a-s) exhibited potent inhibition with IC50 values in the range of 13.70 ± 0.25 µM to 47.30 ± 0.86 µM. Among all the derivatives 5p displayed highest inhibitory activity. Simultaneously, in silico analysis were performed and compared with standard drug (Methotrexate) to predict the binding affinity and interaction pattern of synthesized compounds with DHFR active site. SAR analysis was done to elucidate how structural modifications impact compound’s biological activity, guiding the rational design of potent and selective drug candidates for targeted diseases. These findings may provide a comprehensive assessment of 4-piperdine-based thiosemicarbazones as DHFR inhibitors and contribute to the development of novel therapeutics targeting DHFR-associated diseases.

Sequential Knoevenagel condensation/cyclization using cyclic active methylene compounds such as Meldrum's acid have been studied. The reaction of 2-(1-phenylvinyl)benzaldehyde and Meldrum's acid, dimedone, or 1,3-indandione with piperidine/AcOH or L-proline at room temperature for 17–18 h gave cyclized indene derivatives in 63–80% yield. The reaction of 2-(3,5-dimethoxyphenyl)benzaldehyde and Meldrum's acid at room temperature for 17 h gave a fluorene derivative in 98% yield. Furthermore, the reaction of 2-(3,5-dimethoxybenzyl)benzaldehyde and Meldrum's acid with piperidine at room temperature for 18 h gave a dihydroanthracene derivative bearing Meldrum's acid in 83% yield. The reaction of 2-(3,5-dimethoxybenzyl)benzaldehyde and Meldrum's acid with piperidine at 110 °C for 2 h gave Meldrum's acid fragmentated dihydroanthracene derivative in 48% yield. The reaction mechanisms of the cyclization steps and Meldrum's acid fragmentation have been examined by the DFT calculations. [ABSTRACT FROM AUTHOR]

The article discusses research which investigated physician approaches to the pharmacologic dystonia treatment in people with cerebral palsy. The study surveyed physician approaches regarding medications for dystonia in CP including baclofen, trihexyphenidyl, gabapentin, carbidopa/levodopa, clonazepam, diazepam, clonidine, tetrabenazine, clobazam and cannabidiol. It described physician's prescribing practices and choice of medications for dystonia.

Diabetes mellitus is a severe endocrine disease that affects more and more people every year. Modern medical chemistry sets itself the task of finding effective and safe drugs against diabetes. This review provides an overview of potential antidiabetic drugs based on three heterocyclic compounds, namely morpholine, piperazine, and piperidine. Studies have shown that compounds containing their moieties can be quite effective in vitro and in vivo for the treatment of diabetes and its consequences. [ABSTRACT FROM AUTHOR]

The article focuses on hereditary hyperekplexia (HPX), a rare disorder characterized by exaggerated startle response and generalized muscle stiffness, often presenting in infancy. It discusses the standard treatment with clonazepam and explores the novel use of trihexyphenidyl to alleviate persistent generalized stiffness episodes in patients unresponsive to clonazepam.

In this study, a highly effective microwave‐assisted method employing a multicomponent domino Knoevenagel/phospha‐Michael reaction has been established. This approach facilitates the synthesis of a novel set of pyrazolylphosphonate derivatives in good yields by combining aryl aldehydes with pyrazolones and trialkylphosphites, utilizing piperidine as a Bronsted base catalyst. All pyrazolylphosphonates have been characterized by means of IR, 1H‐NMR, 13C‐NMR, and HRMS analyses and physical methods. This protocol can be characterized by its eco‐friendly nature, exceptional efficiency in terms of product yields, and short reaction times. [ABSTRACT FROM AUTHOR]

A general and useful palladium‐catalyzed [4 + 2] cycloaddition of sulfamate‐derived cyclic imines with γ‐methylidene‐δ‐valerolactones (or 2‐methylidenetrimethylene carbonate) is described. The developed strategy generated diverse sulfamate‐fused piperidine derivatives (or sulfamate‐fused 1,3‐oxazinane rings) in good yields. [ABSTRACT FROM AUTHOR]

Piperidine is an essential moiety of morphine, responsible for the analgesic activity. Among number of other analgesic targets, µ-opioid receptor is still the most focused and therapeutically important in the management of pain. In this study, a series of novel derivatives of 4 amino methyl piperidine were synthesized and explored for analgesic potential against mu opioid receptor. Their structures were elucidated by FT-IR, 1H NMR, and LC-MS followed by in vivo analgesic evaluation by tail-flick method and writhing test. Among all derivatives, HN58 showed excellent analgesic activity (100% inhibition) in writhing test. Furthermore, reduction of HN58 analgesic effect by naloxone suggests its involvement with µ-OR. Molecular docking approach was also utilized to compare the analgesic potential of synthesized derivatives in order to find potent µ-OR inhibitors, we designed five piperidine derivatives with analgesic activity. We have elucidated the binding affinities and binding modes of these piperidine derivatives including standard molecules Morphine, Fentanyl Pethidine and DAMGO revealed a well-known µ-O inhibitor (having binding affinity ranges from −8.13 to −13.37 kcal/mol). All novel derivatives exhibited the remarkable binding score and encapsulated in the binding pocket of transmembraneous helices engaged by the residues Q124, W133, I144, D147, Y148, M151, V236, I296, H297, W318, I322, and Y236. All derivatives revealed excellent binding scores and interaction mechanism as compared to morphine, pethidine, and fentanyl respectively. [ABSTRACT FROM AUTHOR]

When treated with cycloalkylamines (pyrrolidine, piperidine, morpholine, and N-methylpiperazine), polyfluoro-containing benzoic and salicylic acid esters undergo chemoselective nucleophilic aromatic substitution of a fluorine atom in the para position to form 4-(N-cycloalkylamino)-substituted derivatives. The hydrolysis of the latter compounds with alkali in aqueous methanol affords the corresponding acids. Methyl 3,5-difluoro-2-hydroxy-4-(piperidin-1-yl)benzoate exhibits high antibacterial activity against the N. gonorrhoeae strain, which is twice higher than that of the drug spectinomycin. N-Cycloalkyl-substituted polyfluorobenzoic acids do not show analgesic activity. The effect of the esters is comparable with the activity of the drug diclofenac. The studied compounds have a lower acute toxicity compared to the reference drug. [ABSTRACT FROM AUTHOR]

Recent advancements in anion exchange membrane fuel cells (AEMFCs) have been primarily driven by improvements in anion exchange membranes (AEMs). Aryl ether bond‐free membranes have emerged as a promising avenue for enhancing the overall performance of AEMs. In this study, poly (binaphthyl triphenyl piperidine) with different side‐chain degree (PBTP‐s‐x), possesses double cationic groups, aiming at further enhancing overall performance for AEMs. The use of a twisted stereospecific backbone structure of polymerized binaphthyl and triple biphenyl monomer and grafted side chains of piperidine cationic groups not only improves the microphase separation structure of the membrane, but also improves the alkali resistance. Notably, the PBTP‐s‐100 AEMs exhibit exceptional OH− conductivity, reaching up to 138.21 mS cm−1, and show outstanding mechanical properties with a tensile strength of up to 28 MPa. Additionally, PBTP‐s‐100 displays excellent durability, proved by the NMR spectral consistency and over 80 % ion conductivity retention in 1 M NaOH at 60 °C for 4 weeks. And PBTP‐s‐100 exhibits a higher Lowest Unoccupied Molecular Orbital (LUMO) and a larger energy gap for LUMO and Highest Occupied Molecular Orbital (HOMO) by density functional theory calculation, which indicates it possesses sterling alkaline stability. These findings highlight the potential of PBTP‐s‐100 as a highly performing polymer structure suitable for anion exchange membranes, which is capable of significantly enhancing the performance of fuel cells. [ABSTRACT FROM AUTHOR]

The reactivity of complexes [Fe2(μ‐S2)(CO)4L2] (L=CO (1), PPh3 (2)), with lithium alkynylide reagents generated in situ, was investigated. The behavior of the S2‐bridge in these compounds depends on the substitution at the diiron core. The reaction with the hexacarbonyl derivative 1 leads to the formation of the 1,2‐dithiolene bridged complex [Fe2(μ‐SCH=C(R)S)(CO)6] (3R) while the molecule [Fe2(μ‐SH)(μ‐SC≡CR)(CO)4(PPh3)2] (5R), with an open butterfly structure, is isolated when reacting the disubstituted derivative 2. The disubstituted dithiolene complex [Fe2(μ‐SCH=C(Ph)S)(CO)4(PPh3)2] (4Ph) can only be obtained by substitution of carbonyls with PPh3 in 3R. In the presence of piperidine, 5R isomerizes into the 1,1'‐dithiolene bridged derivative 6Ph. The novel compounds 4–6 were synthesized and characterized by IR and NMR spectroscopies. X‐ray crystallographic studies of the dithiolene complexes 3Ph–4Ph allowed their structural analysis. [ABSTRACT FROM AUTHOR]

Two series of novel hybrid heterocyclic compounds that combine the imidazole ring with bioactive piperidine, morpholine or piperazine heterosystems, through a hydrazone unit, were easily obtained by two competitive pathways. Starting from 5‐amino‐4‐cyanoformimidoyl imidazoles and 1‐aminopiperidine, 4‐aminomorpholine or 1‐amino‐4‐methylpiperazine under mild acidic media led to the selective synthesis of 5‐aminoimidazole 4‐carboxamidrazones, whereas the corresponding 4‐hydrazonoyl cyanide derivatives were obtained under stronger acidic conditions. These highly functionalized imidazoles provide convenient synthetic precursors to a vast array of heterocycles with potential pharmaceutical applications. The reaction mechanisms were elucidated on the basis of experimental assays and in silico calculations. The compounds were screened against colorectal cancer HCT116‐p53 wt cell line, and significant IC50 values of 3.69 μM and 4.83 μM were obtained. [ABSTRACT FROM AUTHOR]

In this study, the inhibition effects of aniline molecules of 1-(2-Furylmethyl) piperidine-3-carboxylic acid hydrochloride (molecule 1), and 3-Chloro-4-(3,5-dimethyl-1-piperidinyl) aniline (molecule 2), which contain piperidine ring, on the enzymes of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) and glutathione s-transferase (GST) were investigated. The studies of IC50 and Ki were performed for the inhibitors. All the molecules were found to be good inhibitors for the three enzymes. Molecule 2 was detected to be an effective inhibitory with Ki values of 2.9987±0.2555 for the AChE enzyme and 1.9301±0.2563 for the BChE enzyme. Molecule 1 was found to be another effective molecule with a Ki value of 4.217±0.3759 for the GST enzyme. Ethacrynic acid (EA) and tacrine (TAC) were used as positive inhibitions for enzymes of GST and cholinesterases, respectively. The studied molecules were detected to be more effective compared to the standard compounds. Additionally, enzyme inhibitor interaction was examined theoretically by molecular docking. [ABSTRACT FROM AUTHOR]

Treatment with immune checkpoint inhibitors is effective in various cancers, but may be associated with immune-mediated side effects in other organs. Among the more common ones is gastrointestinal tract involvement, especially colitis. In most patients, colitis is mild or responds to corticosteroid treatment. A smaller proportion of patients, more often those treated with cytotoxic T lymphocyte antigen-4 inhibitors, may have a more severe course of colitis, even life-threatening complications. In these patients, prompt action, timely diagnosis with endoscopic evaluation and early treatment with high-dose corticosteroids and, if ineffective, rescue therapy with biologic agents such as infliximab and vedolizumab are needed. We present three cases from our clinical practice, data on incidence and clinical presentation, current recommendations regarding diagnostic approach and treatment of immune checkpoint inhibitors induced colitis. [ABSTRACT FROM AUTHOR]

Background: Lung cancer ranks first in both cancer incidence and mortality in China. The emergence of novel treatments for ALK-positive NSCLC led to an improvement in survival and quality of life for patients with advanced ALK mutation-positive non-small cell lung cancer (NSCLC). This study sought to assess the cost-effectiveness of 6 tyrosine kinase inhibitors (TKIs)—crizotinib, alectinib, ceritinib, brigatinib, ensartinib, and lorlatinib—as first-line treatments for ALK-positive NSCLC from the perspective of the Chinese health care system. Methods: A Markov model was developed to estimate the cost-effectiveness of these 6 TKIs. In this model, ALK-positive NSCLC patients were initially simulated to receive 1 of the 6 TKIs as first-line therapy, followed by different TKIs as subsequent treatment and salvage chemotherapy as last-line treatment. Survival data were sourced from the latest published clinical trials. Costs were derived from recent national health insurance negotiations and hospital information systems of selected health care facilities. Utilities for healthy states and adverse events were obtained from the literature. One-way and probabilistic sensitivity analysis as well as scenario analysis was conducted to assess the robustness of the results. Results: Compared to ensartinib, crizotinib, alectinib, ceritinib, brigatinib, and lorlatinib demonstrated incremental quality-adjusted life years (QALYs) of −1.13, 0.39, −0.58, −0.09, and 0.35, respectively. The corresponding incremental costs were $10 677, $33 501, −$6426, $2672, and $24 358. This resulted in ICERs of –$9449/QALY, $85 900/QALY, $11 079/QALY, $29 689/QALY and $69 594/QALY, respectively. Conclusion: Crizotinib was considered to be absolutely dominated by ensartinib. Under a willingness-to-pay threshold of $38 223/QALY, ceritinib and brigatinib were cost-effective compared with ensartinib, while lorlatinib and alectinib were not cost-effective when compared with ensartinib. Overall, brigatinib emerged as the most cost-effective treatment among all the options considered. [ABSTRACT FROM AUTHOR]

The catalytic activity of zinc(II) compounds was exploited in the nucleophilic addition of amines to nitriles to form amidines. The reaction systems comprised a Zn(II) starting material [Zn(quin)2(H2O)] (quin− = quinaldinate, an anion of quinaldinic acid), secondary cyclic amine, acetonitrile, and in some cases, methanol. Amines with additional heteroatoms in the ring (thiomorpholine, piperazine) or ring substituents (piperidine derivatives, piperazine derivatives) with different steric and electronic effects were used. The aim of the study was to determine how the nature of the amine affects the formation of amidines. Different types of Zn(II) products were obtained: mono- or diamine complexes, amidine complexes, and also an ionic compound with a protonated amine. In one case, the amidine itself crystallized. A Zn(II) complex with acetamidine was also obtained. Acetamidine was formed from acetonitrile and ammonia, which most likely originated from the hydrolysis of acetonitrile under harsh reaction conditions. The hydrolysis could terminate at the acetamide step, which was confirmed by the isolation of a cocrystal containing acetamide. In the case of piperazine (pz), a polymeric compound with the composition [Zn(quin)2(pz)]n was isolated regardless of the reaction conditions. The same coordination polymer was also observed to form in 1-methylpiperazine, 1-ethylpiperazine, and 1-acetylpiperazine reaction systems, containing piperazine as an inherent impurity. This was unambiguously confirmed by the crystal structure of a cocrystal, [Zn(quin)2(1-Acpz)2]·[Zn(quin)2(pz)]n·4CH3CN, which formed in the 1-acetylpiperazine (1-Acpz) reaction system. [ABSTRACT FROM AUTHOR]

Simple Summary: As the precursor of pepsin, Pepsinogen C (PGC) is the final product of the maturation and differentiation of gastric mucosa cells. The latest bioinformatics analysis found that PGC may play a little-known role in the carcinogenic process, but there is no relevant experimental evidence to prove the effect of PGC on the biological function of cancer cells. In our research, we found PGC may act as a tumor suppressor in the development and metastasis of gastric cancer. PGC can downregulate its interacting protein IQGAP1 and inhibit the Rho-GTPase pathway, thereby participating in the inhibition of gastric cancer cell migration and invasion. Thus, PGC has the potential to be a new therapeutic target for gastric cancer. Aim: This study systematically explored the biological effects and mechanisms of PGC on gastric cancer (GC) cells in vitro and in vivo. Method: The critical biological roles of PGC in GC were assessed via EdU staining, Hoechst staining, flow cytometry, mouse models, CCK-8, wound healing, transwell, and sphere-forming assays. The interaction study with IQ-domain GTPase-activating protein 1 (IQGAP1) was used by Liquid chromatography-mass spectrometry co-immunoprecipitation, immunofluorescence staining, CHX-chase assay, MG132 assay, and qRT-PCR. Results: PGC inhibited the proliferation, viability, epithelial–mesenchymal transition, migration, invasion, and stemness of GC cells and promoted GC cell differentiation. PGC suppressed subcutaneous tumor growth and peritoneal dissemination in vivo. The interaction study found PGC inhibits GC cell migration and invasion by downregulating IQGAP1 protein and IQGAP1-mediated Rho-GTPase signaling suppression. In addition, PGC disrupts the stability of the IQGAP1 protein, promoting its degradation and significantly shortening its half-life. Moreover, the expression levels of PGC and IQGAP1 in GC tissues were significantly negatively correlated. Conclusion: PGC may act as a tumor suppressor in the development and metastasis of GC. PGC can downregulate its interacting protein IQGAP1 and inhibit the Rho-GTPase pathway, thereby participating in the inhibition of GC cell migration and invasion. [ABSTRACT FROM AUTHOR]

Reactions between octa(2,6-fluorophenyl)porphyrazine and pyridine, 2-methylpyridine, morpholine, piperidine, butylamine, tert-butylamine, diethylamine, and triethylamine in a benzene medium have been studied. The acid–base reactions between the macroheterocycle and piperidine or butylamine are slow processes leading to the formation of kinetically stable proton-transfer complexes. The structures of these complexes have been optimized using CAM-B3LYP/cc-pVTZ. The changes in the reactivity of octa(2,6-fluorophenyl)porphyrazine are analyzed as a function of the steric structure and proton-acceptor power of the nitrogenous base. [ABSTRACT FROM AUTHOR]

A new type of the four-component tandem Knoevenagel—Michael reaction was discovered, which used arylaldehydes, N,N′-dimethylbarbituric acid, dimedone, and morpholine or piperidine in organic solvents or in water. The reaction proceeded under mild conditions at room temperature with the formation of a new substituted unsymmetrical polycyclic ionic scaffold in 83–98% yields. The structures of the reaction products were confirmed by X-ray diffraction analysis on the example of two compounds. The further oxidative cyclization of the Knoevenagel—Michael reaction products led to unsymmetrical substituted dihydrofurans spiro-annulated with N,N′-dimethylbarbituric acid. The structures of the synthesized compounds were confirmed by X-ray diffraction analysis. [ABSTRACT FROM AUTHOR]

Stable boroxine-amine adducts comprising dative B←N bond(s) were prepared by mechanochemically-induced reactions of phenylboronic acid (PBA) and amines (pyridine, DMAP, 1Hpyrazole, piperidine, DABCO, hexamethylenetetramine, or 4,4'-bipyridine). In-situ Raman monitoring, ex-situ PXRD and DFT calculations were used for product identification. Stoichiometry of the product (3: 1, 3:2 or 6:1 adduct) was controlled by the amine structure and the molar ratio of the reactants. The 1:2 Hbonded assembly of PBA and 4,4'-bipyridine (bpy) was confirmed as an intermediate in the adduct formation for bpy. Competitive binding experiments indicated that the exchange of the amines in the 3:1 adducts follows the computed adduct stabilities that increase with the amine basicity. Following the DFT prediction, the first adduct with two different amines, DMAP and pip, bound to one boroxine moiety was isolated and structurally characterized. Results show that calculations can be used to predict possible and preferred product(s) and their spectral characteristics. [ABSTRACT FROM AUTHOR]

Linearly fused polycyclic piperidines represent common substructures in natural products and biologically active small molecules. We have devised a Pd‐catalyzed annulation strategy to these compounds that converts readily available 2‐tetralones and indanones into these scaffolds with the potential for control of both enantio‐ and diastereoselectivity. Importantly, these compounds can be chemoselectively functionalized, providing an efficient and robust methodology to these important nitrogen‐containing molecules. [ABSTRACT FROM AUTHOR]

Background: A lack of safety data on postpartum medication use presents a potential barrier to breastfeeding and may result in infant exposure to medications in breastmilk. The type and extent of medication use by lactating women requires investigation. Methods: Data were collected from the CHILD Cohort Study which enrolled pregnant women across Canada between 2008 and 2012. Participants completed questionnaires regarding medications and non-prescription medications used and breastfeeding status at 3, 6 and 12 months postpartum. Medications, along with self-reported reasons for medication use, were categorized by ontologies [hierarchical controlled vocabulary] as part of a large-scale curation effort to enable more robust investigations of reasons for medication use. Results: A total of 3542 mother-infant dyads were recruited to the CHILD study. Breastfeeding rates were 87.4%, 75.3%, 45.5% at 3, 6 and 12 months respectively. About 40% of women who were breastfeeding at 3 months used at least one prescription medication during the first three months postpartum; this proportion decreased over time to 29.5% % at 6 months and 32.8% at 12 months. The most commonly used prescription medication by breastfeeding women was domperidone at 3 months (9.0%, n = 229/2540) and 6 months (5.6%, n = 109/1948), and norethisterone at 12 months (4.1%, n = 48/1180). The vast majority of domperidone use by breastfeeding women (97.3%) was for lactation purposes which is off-label (signifying unapproved use of an approved medication). Non-prescription medications were more often used among breastfeeding than non-breastfeeding women (67.6% versus 48.9% at 3 months, p < 0.0001), The most commonly used non-prescription medications were multivitamins and Vitamin D at 3, 6 and 12 months postpartum. Conclusions: In Canada, medication use is common postpartum; 40% of breastfeeding women use prescription medications in the first 3 months postpartum. A diverse range of medications were used, with many women taking more than one prescription and non-prescription medicines. The most commonly used prescription medication by breastfeeding women were domperidone for off-label lactation support, signalling a need for more data on the efficacy of domperidone for this indication. This data should inform research priorities and communication strategies developed to optimize care during lactation. [ABSTRACT FROM AUTHOR]

Introduction: To introduce a drug to the market, it's not mandatory for it to be more effective and safer than the current treatment for the same condition. Consequently, head-to-head studies between the two best treatments for the same condition are not required, and this could result in a lack of information for patients, clinicians, and decision-makers. This study aims to evaluate the presence of head-to-head studies among the drugs used for the treatment of non-small cell lung cancer (NSCLC). Methods: Taking into account the National Comprehensive Cancer Network (NCCN) guidelines updated to 2022, which list all available treatments for each NSCLC subtype, the search engine Pubmed and the platform clinicaltrials.gov were consulted to find all completed and ongoing head-to-head studies among various treatments for NSCLC. Results: Among the anti-EGFR (epidermal growth factor receptor) drugs, 7 studies were found, with 6 completed and 5 registrational for drug commercialisation. No completed study to date has compared osimertinib and afatinib. For anti-ALK (anaplastic lymphoma kinase) drugs, 7 studies were found, with 5 completed. Alectinib, brigatinib, and lorlatinib have no completed comparison studies, but all were compared with crizotinib. Among various immunotherapy-based regimens, 5 studies were found, with only 1 completed. Therapeutic regimens based on pembrolizumab, atezolizumab, or the combination of nivolumab/ipilimumab have not been compared in studies published to date. Conclusion: There are few head-to-head studies comparing treatments for NSCLC; there are no such studies between the latest generation of drugs. Consequently, ambiguous areas exist due to the lack of comparative studies among the available evidence, preventing the clinician's choice of the most effective treatment and risking the patient receiving suboptimal therapy. Simultaneously, the price of the drug cannot be determined correctly, relying only on indirect evaluations from different trials. To dispel this uncertainty, it would be desirable to initiate a process that brings together the demands derived from clinical practice and clinical research to provide clinicians and patients with the best possible evidence. [ABSTRACT FROM AUTHOR]

The reaction of ethyl 3-aryl-2-cyanoprop-2-enoates with N1,N3-bis(2-methoxyphenyl)propanedi-amide afforded previously unknown products of intramolecular heterocyclization of the primary Michael adducts, ethyl 4-aryl-2-imino-1-(2-methoxyphenyl)-5-[(2-methoxyphenyl)carbamoyl]-6-oxopiperidine-3-car-box-ylates, in 73–90% yields. The product structure was determined by IR and NMR (1H, 13C) spectroscopy. [ABSTRACT FROM AUTHOR]

Benzimidazole-based pyrrole/piperidine analogs (1–26) were synthesized and then screened for their acetylcholinesterase and butyrylcholinesterase activities. All the analogs showed good to moderate cholinesterase activities. Synthesized compounds (1–13) were screened in cholinesterase enzyme inhibition assays and showed AChE activities in the range of IC50 = 19.44 ± 0.60 µM to 36.05 ± 0.4 µM against allanzanthane (IC50 = 16.11 ± 0.33 µM) and galantamine (IC50 = 19.34 ± 0.62 µM) and varied BuChE inhibitory activities, with IC50 values in the range of 21.57 ± 0.61 µM to 39.55 ± 0.03 µM as compared with standard allanzanthane (IC50 = 18.14 ± 0.05 µM) and galantamine (IC50 = 21.45 ± 0.21 µM). Similarly, synthesized compounds (14–26) were also subjected to tests to determine their in vitro AChE inhibitory activities, and the results obtained corroborated that all the compounds showed varied activities in the range of IC50 = 22.07 ± 0.13 to 42.01 ± 0.02 µM as compared to allanzanthane (IC50 = 20.01 ± 0.12 µM) and galantamine (IC50 = 18.05 ± 0.31 µM) and varied BuChE inhibitory activities, with IC50 values in the range of 26.32 ± 0.13 to 47.03 ± 0.15 µM as compared to standard allanzanthane (IC50 = 18.14 ± 0.05 µM) and galantamine (IC50 = 21.45 ± 0.21 µM). Binding interactions of the most potent analogs were confirmed through molecular docking studies. The active analogs 2, 4, 10 and 13 established numerous interactions with the active sites of targeted enzymes, with docking scores of −10.50, −9.3, −7.73 and −7.8 for AChE and −8.97, −8.2, −8.20 and −7.6 for BuChE, respectively. [ABSTRACT FROM AUTHOR]

Novel rhodium‐catalyzed [3+3] annulations of diazoenals and α‐amino ketones has been disclosed here. The reactivity of diazoenals has been switched from carbenoid to vinylogous NH‐insertion by altering acyclic to cyclic α‐amino ketones. In this direction, we report an efficient strategy to synthesize 1,2‐dihydropyridines (DHPs) and fused 1,4‐oxazines. Mechanistic investigation revealed that the formyl group is necessary for carbenoid [3+3] annulation and the cyclohexyl group is the dictating factor for vinylogous NH‐ insertion. The synthetic utility of 1,2‐dihydropyridines was demonstrated by synthesizing piperidine, pyrido[1,2‐a]indole, and 2‐pyridone scaffolds. Further, structural diversification of fused 1,4‐oxazines resulted in the short synthesis of hexahydroquinolin‐2(1H)‐ones, hexahydro quinolines and tetrahydroquinolinones via ring opening rearrangement and a new oxidative deformylation, respectively. [ABSTRACT FROM AUTHOR]

It is known that compounds containing sulfur in their structure have a wide range of biological activities, such as antibacterial, antiallergic, antimicrobial, anticancer, and anticonvulsant. In addition, nitrogen-containing heterocyclic compounds are also found in nature and the structure of drugs. Various compounds, such as piperidine and its derivatives, are also widely used in the synthesis of many drugs. Various Schiff bases have been synthesized in drug development studies, and they have been used in clinical applications as drugs and drug candidates. In this context, the synthesis of new thiophene-based Schiff bases containing piperidine rings is aimed. Green chemistry objectives were adhered to in the syntheses. Thiophene-2-carbaldehyde and piperidine derivatives were used as starting compounds, and new compounds containing thiophene-based piperidine were synthesized without adding any catalyst or solvent to the reaction medium. The desired Schiff base compounds were successfully synthesized in high yield and in a short time. [ABSTRACT FROM AUTHOR]

In this work, we report the synthesis of a new anion exchange membrane based on a Polyketone (PK) functionalized with 1-(3-aminopropyl)piperidine through a solvent-ess Paal-Knorr reaction with a carbonyl (CCO %) conversion of 36%. A one-step castquaternization process by using 1,4-diiodobutane was performed that yielded a homogeneous membrane in a highly reproducible way. The obtained membranes showed good performances in terms of thermal resistance (up to 250°C), water uptake of 21% and ion exchange capacity of 2 meq/g, which support their use as anion exchange membranes for water electrolysers (AEM-WE). [ABSTRACT FROM AUTHOR]

Cholinesterases are important in ensuring hemostasis in our body. Excessive increase in cholinesterase function causes various cholinergic dysfunctions. Alzheimer's is a disease characterized by loss of cholinergic activity, which is especially common in the elderly. One of the cholinesterase inhibitors most commonly used to stop the progression of Alzheimer's disease is donepezil. Due to some side effects of donepezil, the synthesis and design of new analogues that may be alternatives to donepezil are reported in the literature. In this study, molecular docking studies were performed to compare the in silico AChE inhibitory potential of some new structural analogs of donepezil. Molecular docking studies were performed using Autodock4.2 tools. In this study, the hypothesis emerges that especially compound 1 and compound 5 have the potential to inhibit AChE at least as much as donepezil. In silico docking studies showed that donepezil derivatives designed with bioisosteres of the piperidine ring in donepezil have high binding affinity towards acetylcholine esterase. These results need to be confirmed by synthesis of the donepezil analogues designed in the study and in vitro activity measurements. [ABSTRACT FROM AUTHOR]

Nowadays, over 200 countries face a wellbeing emergency because of epidemiological disease COVID-19 caused by the SARS-CoV-2 virus. It will cause a very high effect on the world economy and the worldwide health sector. The present work is an investigation of the newly synthesized (Z)-2,6-bis(4-bromophenyl)-3,3-dimethyl-4-(2-(2,4,6-trichlorophenyl) hydrazono) piperidine (BBDTHP) molecule inhibitory potential against important protein targets of SARS-CoV-2 using computational approaches. For the title compound BBDTHP, spectroscopic characterization like FT-IR, 1H-NMR, 13C-NMR, 1H–1H COSY and 1H–13C COSY spectrum were carried out. The geometry of the compound had been optimized by the DFT method and its results were compared with the X-ray diffraction data. The calculated energies for the Highest occupied molecular orbital (HOMO) and the Lowest unoccupied molecular orbital (LUMO) showed the stability and reactivity of the title compound. The molecular electrostatic potential (MEP) picture was drawn using the same level of theory to visualize the chemical reactivity and charge distribution on the molecule. Molecular docking study performed for the synthesized compound revealed an efficient interaction with the COVID-19 protease and resulted in good activities. We hope the present study would help workers in the field to develop potential vaccines and therapeutics against the novel coronavirus. Virtual ADME studies were carried out as well and a relationship between biological, electronic and physicochemical qualifications of the target compound was determined. Toxicity prediction by computational technique for the title compound was also carried out. From the molecular dynamic simulations study, we confirmed hydrogen bonding interactions and stability of the molecule. [ABSTRACT FROM AUTHOR]

The irritable bowel syndrome (IBS) is a functional gastrointestinal disorder (FGID), whose prevalence has widely increased in pediatric population during the past two decades. The exact pathophysiological mechanism underlying IBS is still uncertain, thus resulting in challenging diagnosis and management. Experts from 4 Italian Societies participated in a Delphi consensus, searching medical literature and voting process on 22 statements on both diagnosis and management of IBS in children. Recommendations and levels of evidence were evaluated according to the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. Consensus was reached for all statements. These guidelines suggest a positive diagnostic strategy within a symptom-based approach, comprehensive of psychological comorbidities assessment, alarm signs and symptoms' exclusion, testing for celiac disease and, under specific circumstances, fecal calprotectin and C-reactive protein. Consensus also suggests to rule out constipation in case of therapeutic failure. Conversely, routine stool testing for enteric pathogens, testing for food allergy/intolerance or small intestinal bacterial overgrowth are not recommended. Colonoscopy is recommended only in patients with alarm features. Regarding treatment, the consensus strongly suggests a dietary approach, psychologically directed therapies and, in specific conditions, gut-brain neuromodulators, under specialist supervision. Conditional recommendation was provided for both probiotics and specific fibers supplementation. Polyethylene glycol achieved consensus recommendation for specific subtypes of IBS. Secretagogues and 5-HT4 agonists are not recommended in children with IBS-C. Certain complementary alternative therapies, antispasmodics and, in specific IBS subtypes, loperamide and rifaximin could be considered. [ABSTRACT FROM AUTHOR]

Previously synthesized ethyl 2-benzamido-4-(1,4-benzodioxan-2-yl)thiophene-3-carboxylates were cyclized to 2-aryl-3-aminothieno[2,3-d]pyrimidin-4(1H)-ones by the action of hydrazine hydrate. The con-densation of ethyl 2-amino-4-(1,4-benzodioxan-2-yl)thiophene-3-carboxylate with chloroacetyl chloride gave the corresponding N-substituted 2-chloroacetamide which reacted with piperidine and morpholine to produce 2-aminoacetamides, and the latter were also subjected to cyclization with hydrazine hydrate to obtain 3-amino-thienopyrimidin-4-one derivatives. The synthesized compounds were tested for antihypoxic activity. [ABSTRACT FROM AUTHOR]

Inhibition of glycoside hydrolases has widespread application in the treatment of diabetes. Based on our previous findings, a series of dihydrofuro[3,2-b]piperidine derivatives was designed and synthesized from D- and L-arabinose. Compounds 32 (IC50 = 0.07 μM) and 28 (IC50 = 0.5 μM) showed significantly stronger inhibitory potency against α-glucosidase than positive control acarbose. The study of the structure–activity relationship of these compounds provides a new clue for the development of new α-glucosidase inhibitors. [ABSTRACT FROM AUTHOR]

Pain and anesthesia are a problem for all physicians. Scientists from different countries are constantly searching for new anesthetic agents and methods of general anesthesia. In anesthesiology, the role and importance of local anesthesia always remain topical. In the present work, a comparative analysis of the results of pharmacological studies on models of the conduction and terminal anesthesia, as well as acute toxicity studies of the inclusion complex of 1-methyl-4-ethynyl-4-hydroxypiperidine (MEP) with β-cyclodextrin, was carried out. A virtual screening and comparative analysis of pharmacological activity were also performed on a number of the prepared piperidine derivatives and their host–guest complexes of β-cyclodextrin to identify the structure–activity relationship. Various programs were used to study biological activity in silico. For comparative analysis of chemical and pharmacological properties, data from previous works were used. For some piperidine derivatives, new dosage forms were prepared as beta-cyclodextrin host–guest complexes. Some compounds were recognized as promising local anesthetics. Pharmacological studies have shown that KFCD-7 is more active than reference drugs in terms of local anesthetic activity and acute toxicity but is less active than host–guest complexes, based on other piperidines. This fact is in good agreement with the predicted results of biological activity. [ABSTRACT FROM AUTHOR]