Medicinal Chemistry Research最新文献

{"title":"From danger to resolution: targeting purinergic signaling in CNS diseases","authors":"Camille Degryse,&nbsp;Kirti Gupta,&nbsp;Luc Buée,&nbsp;Thierry Burnouf,&nbsp;David Blum,&nbsp;Ming-Li Chou","doi":"10.1007/s00044-026-03583-w","DOIUrl":"10.1007/s00044-026-03583-w","url":null,"abstract":"<div><p>The central nervous system (CNS) is a dynamic immunological environment, where specialized interfaces, immune reservoirs, and metabolic clearance pathways, such as the glymphatic system, orchestrate immune surveillance and homeostasis. Within this intricate network, purinergic signaling, mediated by nucleotides like ATP and adenosine, emerges as a critical regulator of immune responses, inflammation resolution, and tissue repair. Adenosine, drives immunosuppression and immune exhaustion, shaping the balance between neuroprotection and neurodegeneration. Purinergic signaling influences a diverse array of cells, including platelets, neutrophils, dendritic cells, lymphocytes, macrophages/microglia, astrocytes, oligodendrocytes as well as neurons, each contributing uniquely to CNS immune dynamics. Dysregulation of this signaling network is implicated in major neurodegenerative and neurological diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), stroke, and traumatic brain injury (TBI). Recent advances in therapeutic strategies targeting purinergic receptors, such as A_2AR and P2X₇, have demonstrated promising clinical potential, offering new avenues for immunomodulation and neuroprotection. This review synthesizes current understanding of purinergic signaling in CNS immunity, explores its role in disease pathogenesis, and discusses innovative therapeutic approaches. By framing purinergic signaling as a tunable “rheostat”, we highlight its potential to shift the CNS from danger to resolution, paving the way for precision immunotherapies in neurological disorders.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"35 10","pages":"2007 - 2027"},"PeriodicalIF":3.5,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00044-026-03583-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vepdegestrant: the first FDA-approved oral PROTAC and a milestone in targeted protein degradation","authors":"Jeffrey Yang,&nbsp;Longqin Hu","doi":"10.1007/s00044-026-03622-6","DOIUrl":"10.1007/s00044-026-03622-6","url":null,"abstract":"<div><p>Vepdegestrant (ARV-471, Veppanu) represents an important milestone in targeted protein degradation (TPD) as the first FDA-approved heterobifunctional proteolysis-targeting chimera (PROTAC). Designed to selectively degrade estrogen receptor α (ERα) through recruitment of the cereblon E3 ubiquitin ligase, vepdegestrant provides an event-driven approach to targeting ERα, including clinically relevant estrogen receptor-1 (ESR1)-mutated forms associated with endocrine therapy resistance. Its oral bioavailability and pharmacological properties enabled clinical development in patients with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1-mutated advanced or metastatic breast cancer. In clinical studies, vepdegestrant improved progression-free survival compared with fulvestrant in this patient population, supporting the therapeutic potential of PROTAC-mediated protein degradation. The approval of vepdegestrant provides clinical and regulatory validation of the PROTAC modality and offers important medicinal chemistry lessons for the design and development of next-generation degraders.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"35 11","pages":"2114 - 2119"},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00044-026-03622-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Baxdrostat (Baxfendy®), a first-in-class aldosterone synthase inhibitor approved for adults with uncontrolled hypertension","authors":"Ahmed R. Ali,&nbsp;Longqin Hu","doi":"10.1007/s00044-026-03620-8","DOIUrl":"10.1007/s00044-026-03620-8","url":null,"abstract":"<div><p>Despite the availability of multiple antihypertensive therapies, many patients remain unable to achieve adequate blood pressure control. Excess aldosterone is a key contributor to resistant and uncontrolled hypertension. Baxdrostat (Baxfendy^®), a first-in-class selective aldosterone synthase (CYP11B2) inhibitor, was approved on May 15, 2026, for use in adults with inadequately controlled hypertension receiving other antihypertensive medications. Unlike mineralocorticoid receptor antagonists, baxdrostat reduces aldosterone biosynthesis while preserving cortisol production, offering a distinct mechanism of action. In phase 3 clinical trials, once-daily baxdrostat (1–2 mg) produced placebo-adjusted reductions of ~ 9–10 mmHg in seated systolic blood pressure. Hyperkalemia was generally manageable, with no clinically meaningful cortisol suppression observed. These findings support baxdrostat as a promising new option for patients with difficult-to-control hypertension.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"35 11","pages":"2109 - 2113"},"PeriodicalIF":3.5,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00044-026-03620-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design and biological evaluation of sulfonamide–chalcone hybrids with in vitro tumor-selective cytotoxicity against oral squamous cell carcinoma: SAR, QSAR, and in silico ADME studies","authors":"Gulsen Ozli,&nbsp;Hiroshi Sakagami,&nbsp;M. Fatih Polat,&nbsp;Cavit Kazaz,&nbsp;Kota Kurosaki,&nbsp;Yoshihiro Uesawa,&nbsp;Kaito Inden,&nbsp;Halise Inci Gul","doi":"10.1007/s00044-026-03624-4","DOIUrl":"10.1007/s00044-026-03624-4","url":null,"abstract":"<div><p>Multidrug resistance and off-target toxicity remain major challenges in the treatment of oral squamous cell carcinoma (OSCC). In this study, sulfonamide-chalcone hybrids were designed by combining the chalcone scaffold with a benzenesulfonamide moiety to explore tumor-selective cytotoxicity and structure-activity relationships. Thirty-two N-(4-(3-(aryl)prop-2-enoyl)phenyl)benzenesulfonamide derivatives, including 17 previously unreported compounds, were synthesized via base-catalyzed Claisen-Schmidt condensation and characterized by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry. Cytotoxicity was evaluated against the human OSCC cell lines Ca9-22 and HSC-2 and non-malignant human gingival fibroblasts and human pulp cells. Compounds <b>5</b>, <b>13</b>, <b>21</b>, <b>30</b>, and <b>32</b> showed the most favorable activity/selectivity profiles, with 50% cytotoxic concentration values of 1.6–2.2 µM against Ca9-22 cells and tumor-selectivity index values of 14.6–21.1. Structure-activity relationship analysis indicated that meta- and <i>para</i>-substitution patterns generally favored tumor-selective cytotoxicity, whereas bulky <i>ortho</i>-substituents reduced activity. Descriptor-based quantitative structure-activity relationship analysis suggested associations between cytotoxicity and molecular shape, polarizability, electronic properties, polarity, and surface descriptors. In silico studies indicated variable gastrointestinal absorption among the selected lead compounds, while none were predicted to permeate the blood–brain barrier. The selected leads also complied with Lipinski’s Rule of Five. Overall, these findings suggest that sulfonamide–chalcone hybrids represent potentially useful tumor-selective cytotoxic scaffolds for further OSCC-focused optimization.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"35 11","pages":"2318 - 2338"},"PeriodicalIF":3.5,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimization of a bis-imine scaffold as a glyoxalase I inhibitor: synthesis, SAR, and docking studies","authors":"Buthina A. Al-Oudat,&nbsp;Farah B. Al-Omari,&nbsp;Suaad A. Audat,&nbsp;Nizar A. Al-Shar’i,&nbsp;Qosay A. Al-Balas","doi":"10.1007/s00044-026-03626-2","DOIUrl":"10.1007/s00044-026-03626-2","url":null,"abstract":"<div><p>Glyoxalase I (Glo-I) enzyme is a validated anticancer target due to its role in methylglyoxal detoxification and its association with tumor progression and drug resistance. Inhibition of Glo-I promotes the accumulation of toxic metabolites and can trigger apoptosis in cancer cells. Building on our previously reported bis-imine Glo-I inhibitor N<b>3</b> (IC₅₀ = 0.89 ± 0.06 µM), which contains two pyrogallol moieties linked <i>via</i> para-positioned imines on a central benzene linker, the present study introduces a focused scaffold-optimization strategy aimed at defining the structural elements required for stronger Glo-I inhibition. Structural simplification of N3, through removal of the central benzene linker, generated compound <b>8a</b>, a simplified bis-imine analogue with two-fold improved potency (IC₅₀ = 0.46 ± 0.10 µM). This enhancement was attributed to preserved hydrogen bonding capacity and improved Zn²⁺ chelation within Glo-I active site. A comprehensive structure–activity relationship (SAR) investigation of compound <b>8a</b> and its analogues demonstrated that the number, position, and free phenolic character of the hydroxyl groups are critical determinants of activity, mainly by supporting hydrogen bonding and bidentate Zn²⁺ coordination. Masking the hydroxyl groups abolished activity, whereas selected alternative chelating groups preserved moderate inhibition, highlighting the importance and flexibility of metal-binding interactions. Importantly, replacement of the bis-imine with amide-imine linker, or reduction to mono-imine analogues, reduced potency, confirming that the bis-imine linker is a key pharmacophoric feature for optimal Glo-I inhibition. Molecular docking further rationalized these findings by identifying the essential interactions with Zn²⁺, polar residues at the active site entrance, and the hydrophobic pocket. Overall, this study provides a clear innovative-driven SAR model for bis-imine-based Glo-I inhibitors and identified compound 8a as an optimized lead for the future design of anticancer candidates targeting Glo-I enzyme.</p><p>Clinical trial number: not applicable.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"35 11","pages":"2300 - 2317"},"PeriodicalIF":3.5,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149073145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glypican-3-targeted bioconjugates for hepatocellular carcinoma: design, engineering, and translational applications","authors":"Yi Liu,&nbsp;Jiaying Zhu,&nbsp;Haolei Yu,&nbsp;Chenyu Wang,&nbsp;Yue You,&nbsp;Zixuan Hong,&nbsp;Chenbo Zhang,&nbsp;Chenpengyu Zhang,&nbsp;Zhihao Zhang","doi":"10.1007/s00044-026-03625-3","DOIUrl":"10.1007/s00044-026-03625-3","url":null,"abstract":"<div><p>Hepatocellular carcinoma (HCC) is among the most prevalent malignancies and remains a leading cause of cancer-related mortality worldwide. Because early-stage HCC often has a silent clinical course and current surveillance strategies remain imperfect, many patients with HCC are diagnosed at an intermediate or advanced stage. In addition, the high rates of recurrence and metastasis contribute to the persistently poor overall prognosis. Glypican-3 (GPC3) is minimally expressed in normal adult liver tissue, but is frequently upregulated in HCC. However, several major barriers remain, including intratumoral expression heterogeneity, the challenge of achieving stable delivery under conditions of high intrahepatic background, and the lack of robust clinical evidence supporting combined diagnostic and therapeutic strategies. In this review, we summarize the biological basis of GPC3 and recent advances in its application in HCC, with particular emphasis on the development of multiple targeting platforms, including peptides, single-chain variable fragments (scFvs), nanobodies, and full-length antibodies. Our translational decision framework evaluates these platforms not only by absolute tumor uptake but also by tumor-to-liver (T/L) ratio, tumor retention, organ dosimetry, conjugation homogeneity, and manufacturability. Looking ahead, GPC3 molecular imaging may support patient selection, treatment planning, and the evidence-based optimization of combination strategies.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"35 11","pages":"2206 - 2225"},"PeriodicalIF":3.5,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149073098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pantoprazole as a potential repurposed drug targeting the adenosinergic system in esophageal cancer","authors":"Adriana Simioni,&nbsp;Rafael D Weimer,&nbsp;Julia B de Souza,&nbsp;Isadora V Citrini,&nbsp;Julia A da Rosa,&nbsp;Kaline Cardoso,&nbsp;Maria E Delawi,&nbsp;Luis FSM Timmers,&nbsp;Fernanda B Morrone","doi":"10.1007/s00044-026-03618-2","DOIUrl":"10.1007/s00044-026-03618-2","url":null,"abstract":"<div><p>Esophageal cancer remains a major global health burden and is associated with poor prognosis. Adenosine signaling, particularly through CD73 and P1 receptors, contributes to tumor progression and immune modulation. Pantoprazole, a proton pump inhibitor widely used in clinical practice, has recently been suggested as a potential modulator of adenosinergic pathways. This study investigated the ability of pantoprazole to modulate adenosine signaling. In silico docking analyses were performed to assess the binding of pantoprazole to adenosine P1 receptors and CD73, followed by in vitro assays using esophageal adenocarcinoma (OE33) and squamous cell carcinoma (KYSE450) cell lines to evaluate cell growth, adenosinergic signaling, and tumor-related cellular functions following pantoprazole treatment. Docking analyses identified CD73 and P1 receptors, particularly A_2A, as favorable molecular targets for pantoprazole. Pantoprazole significantly reduced proliferation and metabolic activity in both cell lines in a concentration-dependent manner, with pronounced inhibition of clonogenic survival in adenocarcinoma cells. Pantoprazole altered P1 receptor expression, particularly A_2A, and pharmacological antagonism supported the involvement of these receptors in its antiproliferative effects. Additionally, pantoprazole modulated CD73 expression and reduced cell adhesion and MMP‑2 expression. These findings indicate that pantoprazole exerts antitumor effects by modulating the CD73–adenosine–P1 receptor axis, supporting its potential repurposing as an adjunctive strategy for the treatment of esophageal adenocarcinoma.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"35 10","pages":"2094 - 2108"},"PeriodicalIF":3.5,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00044-026-03618-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149056772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of pipernonaline from Piper retrofractum on memory disorder in mice and neurite outgrowth activity of PC12 cells","authors":"Runa Fujimoto,&nbsp;Yuzuki Irie,&nbsp;Tohru Mitsunaga,&nbsp;Kosei Yamauchi","doi":"10.1007/s00044-026-03617-3","DOIUrl":"10.1007/s00044-026-03617-3","url":null,"abstract":"<div><p>In this study, we discovered compounds comprising a piperidine skeleton in <i>Piper retrofractum;</i> the compounds exhibit PC12 dendrite elongation activity. Furthermore, we examined the structure-activity relationship by comparing the activities of the isolated compounds <b>1</b>, <b>3–7</b>. Among the isolated compounds, two alkaloids (6 and 7) displayed significant neurite outgrowth (NOG) effects in the presence of 5 ng/mL nerve growth factor (NGF) in a dose-dependent manner. Comparison of the activity of 3 (Pipercide; 1.8% NOG positive at 100 µM), 6 (Dehydropipernonaline; 21.1% NOG positive at 100 µM), and 7 (Pipernonaline; 24.3% NOG positive at 100 µM) (Nobiletin; 25.4% at 50 µM as positive control) demonstrated that the piperidine skeleton is key to NOG activity. Furthermore, the carbon chain length and number of double bonds influence NOG activity. Moreover, the Barnes maze test showed that oral administration of compound 7 in mice improved memory disorders induced by scopolamine and corticosterone. These results provide extremely valuable foundational knowledge for elucidating the cognitive function-improving effects of P. retrofractum, a food spice.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"35 11","pages":"2269 - 2282"},"PeriodicalIF":3.5,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149035957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repurposing antifolates as G9a methyltransferase inhibitors for potential Alzheimer’s disease therapeutics via 3D QSAR/pharmacophore mapping and experimental validations","authors":"Abhisek Jana,&nbsp;Aina Bellver-Sanchis,&nbsp;Koushik Barman,&nbsp;Christian Griñán-Ferré,&nbsp;Deb Ranjan Banerjee","doi":"10.1007/s00044-026-03621-7","DOIUrl":"10.1007/s00044-026-03621-7","url":null,"abstract":"<div><p>Herein, we report a systematic ML-embedded virtual screening strategy for the repurposing of antifolates (hTS inhibitors) targeting Histone Lysine Methyltransferase (G9a/EHMT2), with experimental validation. Three pharmacophore models (3D QSAR, Common Feature, and Interaction), derived from known G9a inhibitors, were used in a database mining of the 1120 hTS inhibitors from the ChEMBL database. Candidates were filtered using a multi-tier screening strategy based on fit values, drug-likeness, ADMET, and TOPKAT criteria, followed by molecular docking to assess interactions with G9a’s active site, including compounds such as UNC0642 and Raltitrexed as references. The top candidates were selected for strong docking scores, the ability to form at least three hydrogen bonds, and interaction with the lysine-binding tunnel. Among these, Pemetrexed exhibited a binding mode similar to Raltitrexed, forming critical hydrogen bonds and pi interactions with residues Leu1086, Ser1084, Tyr1154, Arg1157, and Phe1158, indicating its potential as a G9a inhibitor. Further analyses of RMSD, RMSF, ROG, and protein-ligand interactions confirmed the stability of Pemetrexed, and MM-GBSA binding energy calculations, along with residue-wise decomposition analysis, supported its strong affinity for G9a. An in vitro assay of Pemetrexed revealed G9a inhibitory activity with an IC₅₀ of 304.90 nM, demonstrating its potency. Additionally, Pemetrexed exhibits lower activity against the G9a-like methyltransferase GLP than the references, confirming the compound’s preferential activity for G9a over GLP. Furthermore, Pemetrexed improves the locomotor deficits associated with <i>Aβ</i> expression in <i>C. elegans</i> CL2006 worms in a dose-dependent manner, showing its potential as an epigenetic therapeutic for Alzheimer’s Disease.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"35 11","pages":"2283 - 2299"},"PeriodicalIF":3.5,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149035970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An updated review of enantioselective syntheses and biological actions of carbanucleosides","authors":"Sheila I. de Diego Saadia,&nbsp;Sergio H. Szajnman,&nbsp;Juan B. Rodriguez","doi":"10.1007/s00044-026-03623-5","DOIUrl":"10.1007/s00044-026-03623-5","url":null,"abstract":"<div><p>Carbocyclic nucleosides are nucleoside analogues where the oxygen atom of the furanose ring is replaced by a methylene group, in many cases a substituted methylene moiety, giving rise to metabolically stable nucleosides analogues that are recognized by the same enzymes that interact with canonical nucleosides. In this article, we were focused on the relevant features of the chemistry and biological properties of this family of compounds emphasizing synthetic aspects to access carbocyclic nucleosides enantioselectively and a comprehensive panorama of their biological properties. Molecular recognition outlook of enzymes of pharmacological importance are discussed. The influence of sugar conformation and puckering in modulating the biological activity and the use of carbanucleosides are illustrated.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"35 10","pages":"1975 - 2006"},"PeriodicalIF":3.5,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149035985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}