MEDICINAL CHEMISTRY RESEARCH药物化学研究
MEDICINAL CHEMISTRY RESEARCH(英文缩写 MED CHEM RES),ISSN 1054-2523,eISSN 1554-8120,中文译名:药物化学研究 是一本学术期刊。本页汇总该期刊的最新影响因子、分区信息以及最新收录于 PubMed 的文献,帮助您快速了解期刊全貌。
发文量统计区间：2025-11-01 至 2026-10-31，按本站收录文献的发表日期统计。
期刊介绍
历年影响因子趋势
| JCR 数据年份 | 影响因子 | JCR 分区 |
|---|---|---|
| 2021 | 2.351 | Q4 |
| 2022 | 2.600 | Q3 |
| 2023 | 2.600 | Q3 |
| 2024 | 3.100 | Q3 |
| 2025 | 3.500 | Q2 |
MEDICINAL CHEMISTRY RESEARCH 最新收录文献
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1. Vepdegestrant: the first FDA-approved oral PROTAC and a milestone in targeted protein degradation.
PMID:期刊:日期:2026-10-01Vepdegestrant (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.
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2. 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.
PMID:期刊:日期:2026-09-29Multidrug 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 5, 13, 21, 30, and 32 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 para-substitution patterns generally favored tumor-selective cytotoxicity, whereas bulky ortho-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.
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3. {"_":"Baxdrostat (Baxfendy), a first-in-class aldosterone synthase inhibitor approved for adults with uncontrolled hypertension.","sup":["®"]}
3. {"_":"巴曲司他（Baxfendy），首个醛固酮合酶抑制剂，获批用于成人未控制高血压。","sup":["®"]}PMID:期刊:日期:2026-09-29Despite 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.
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4. Pantoprazole as a potential repurposed drug targeting the adenosinergic system in esophageal cancer.
PMID:期刊:日期:2026-09-25Esophageal 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, 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, 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.
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5. An updated review of enantioselective syntheses and biological actions of carbanucleosides.
5. 碳环核苷的对映选择性合成及生物作用的最新综述PMID:期刊:日期:2026-09-24Carbocyclic 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. The image presents a typical nucleoside structure at the center, with six chemical compounds branching out from it, each labeled and connected by arrows. These compounds are variations or derivatives of the nucleoside, including carbanucleosides bearing a sulfur atom in the sugar ring, abacavir, neplanocin C, deazaneplanocin A, and a dopamine uptake inhibitor. Each compound is shown with its molecular structure, highlighting differences in the sugar ring or attached groups relative to the typical nucleoside.
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6. Peptide-based allosteric modulators of AMPA receptors: design, docking and ligand-receptor interactions.
PMID:期刊:日期:2026-09-24Neurodegenerative diseases are one of the most pressing challenges of modern medicine, a problem from which no one is immune. Many medications used to treat dementia are ineffective in eliminating the root cause of pathogenesis, or exhibit a number of side effects. Great interest has been shown in positive allosteric modulators (PAMs) of AMPA receptors and PAM-43 is one of the most promising PAMs to date. Peptide allosteric modulators are another promising area of AMPA receptor PAMs. There are numerous cases where peptide-based drugs have a gentler effect and do not cause negative side effects or addiction with prolonged use. Here we designed and synthesized two peptide structures, potential PAMs of AMPA receptors. Our studies have shown that tetrapeptide WPPW and its derivative Boc-WPPW are stable enough to bind a target receptor and do bind to it. Molecular docking of the peptides and PAM-43 revealed several specific binding sites on AMPA receptor, some of which partially overlap. These peptides notably modulate the interaction of [H]PAM-43 at various sites of its specific binding. WPPW partially blocks [H]PAM-43 binding at both its specific sites (high- and low-affine) in a dose-dependent manner. At certain concentrations, Boc-WPPW enhances the exposure of additional binding sites of PAM-43 that may be located not only on AMPA receptors. The peptides WPPW and Boc-WPPW may be of interest as AMPA receptor potential allosteric modulators or cofactor molecules.
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7. Repurposing antifolates as G9a methyltransferase inhibitors for potential Alzheimer's disease therapeutics via 3D QSAR/pharmacophore mapping and experimental validations.
7. 通过三维定量构效关系/药效团映射及实验验证，将抗叶酸药物重新定位为G9a甲基转移酶抑制剂，用于潜在的阿尔茨海默病治疗PMID:期刊:日期:2026-09-24Herein, 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 IC 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 Aβ expression in C. elegans CL2006 worms in a dose-dependent manner, showing its potential as an epigenetic therapeutic for Alzheimer's Disease.
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8. Effect of pipernonaline from Piper retrofractum on memory disorder in mice and neurite outgrowth activity of PC12 cells.
PMID:期刊:日期:2026-09-24In this study, we discovered compounds comprising a piperidine skeleton in Piper retrofractum; the compounds exhibit PC12 dendrite elongation activity. Furthermore, we examined the structure-activity relationship by comparing the activities of the isolated compounds 1, 3-7. 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.
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9. Artificial intelligence-assisted lead optimization in drug discovery: bridging computational advances and translational challenges.
PMID:期刊:日期:2026-09-17Lead optimization is a resource-intensive stage of drug discovery requiring the simultaneous optimization of potency, selectivity, pharmacokinetics, safety, and synthetic feasibility. Although artificial intelligence (AI) and machine learning (ML) have substantially advanced predictive modeling, virtual screening, de novo molecular design, and multiparameter optimization, their translation into routine medicinal chemistry remains challenging. This review critically examines current AI approaches for lead optimization, emphasizing the gap between computational benchmark performance and practical medicinal chemistry applications. Recent advances in graph neural networks (GNNs), transformer architectures, diffusion models, and chemical foundation models have expanded AI-assisted molecular design and property prediction. We further discuss emerging concepts including data-centric AI, uncertainty quantification, trustworthy AI, the AI optimization paradox, and the shift from molecular prediction toward scientific decision-making as key determinants of successful implementation. Despite increasing industrial adoption, AI remains dependent on high-quality experimental data, model generalizability, and rigorous experimental validation. We conclude that future progress will depend less on increasingly sophisticated algorithms than on trustworthy AI systems that improve scientific decision-making within iterative lead optimization workflows and ultimately enhance translational success in drug discovery.
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10. Probing novel azole-sulfonamide urea/thiourea conjugates as multitarget inhibitors of AChE and hCAs (I and II): synthesis, in vitro, and in silico studies.
PMID:期刊:日期:2026-09-17A series of 30 novel azole-sulfonamide urea and thiourea conjugates was rationally designed and synthesized as potential multitarget inhibitors of acetylcholinesterase (AChE) and the human carbonic anhydrase isoforms hCA I and hCA II. The molecular design combined azole-based heterocyclic scaffolds with the classical sulfonamide zinc-binding pharmacophore through urea or thiourea linkers. The synthesized compounds were characterized by FT-IR, H NMR, C NMR, and high-resolution mass spectrometry and subsequently evaluated in vitro against the three target enzymes. Several derivatives exhibited potent nanomolar inhibitory activity. Compounds 11, 6, 26, and 16 were the most active AChE inhibitors, with IC₅₀ values of 23.89, 30.13, 34.65, and 36.47 nM, respectively. Compounds 25, 26, 29, and 20 displayed the strongest inhibition of hCA I, with IC₅₀ values ranging from 40.76 to 46.82 nM, whereas compounds 11 and 17 were the most active against hCA II, both exhibiting an IC₅₀ value of 57.75 nM. Selectivity analysis based on the IC₅₀(hCA I)/IC₅₀(hCA II) ratio indicated limited isoform discrimination overall, with selectivity indices ranging from 0.42 to 1.26. Most derivatives showed a modest relative preference toward hCA I, whereas compounds 13, 17, 18, and 21 displayed modest preference toward hCA II, with compound 17 showing the highest hCA II selectivity index (SI = 1.26). Notably, compounds 11 and 26 showed a well-balanced multitarget profile across all three tested enzymes. Molecular docking and MM-GBSA calculations suggested plausible binding modes involving hydrogen bonding, aromatic interactions, hydrophobic contacts, and, for selected carbonic anhydrase complexes, sulfonamide-mediated coordination with the catalytic Zn²⁺ ion. Overall, the experimental and computational findings identify azole-sulfonamide urea/thiourea conjugates as promising scaffolds for the further development of multitarget enzyme inhibitors and provide preliminary structure-activity insights for subsequent optimization.