Mini reviews in medicinal chemistry最新文献

{"title":"Heat Shock Protein 90 as a Master Regulator of Multidrug Resistance: Small-molecule Inhibitors, Prodrugs, Hybrid Molecules, Antibody-drug Conjugates, and Nanotechnology-based Delivery Systems.","authors":"Sundeep Kadasi, Aishwarya Avinash Kholkumbe, Chandraprabhu Jangme, Vrushabh Sunil Patil, Rameshwar Ardad, Shweta Omkar Hodage","doi":"10.2174/0113895575463212260915061250","DOIUrl":"https://doi.org/10.2174/0113895575463212260915061250","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Multidrug Resistance (MDR) remains a major obstacle to effective cancer chemotherapy, driven by multiple interconnected mechanisms, including overexpression of ATP-binding Cassette (ABC) transporters, enhanced DNA repair, apoptosis evasion, and protumorigenic microenvironmental factors. Heat Shock Protein 90 (HSP90) has emerged as a master regulator of MDR by chaperoning multiple client proteins involved in drug efflux, survival signaling pathways, and cellular stress responses. These mechanisms collectively decrease intracellular drug accumulation and promote tumor cell survival, leading to therapeutic failure. This review aims to summarize HSP90-targeted therapeutic strategies for overcoming MDR in cancer and evaluate their mechanistic basis, efficacy, and translational potential.</p><p><strong>Methods: </strong>A systematic literature search was conducted in PubMed, Scopus, Web of Science, and Google Scholar up to 2010-2026. Keywords included \"HSP90,\" \"multidrug resistance,\" \"cancer,\" \"HSP90 inhibitors,\" \"prodrug,\" \"ADC,\" and \"nanotechnology,\" combined using Boolean operators. Relevant preclinical and clinical studies on HSP90-targeted strategies to overcome MDR were included, while duplicates and studies that were irrelevant or insufficiently detailed were excluded. Eligible studies were screened and analyzed for mechanisms, therapeutic outcomes, and limitations.</p><p><strong>Results: </strong>Small-molecule HSP90 inhibitors, including geldanamycin derivatives and resorcinol-based compounds, demonstrate potential in destabilizing MDR-associated client proteins such as P-glycoprotein, MRP1, BCRP, and survival kinases, thereby restoring sensitivity of resistant cancer cells to chemotherapy. Prodrug strategies improve bioavailability and reduce systemic toxicity while preserving HSP90 inhibitory activity. Hybrid molecules that integrate HSP90 inhibition with complementary mechanisms, such as HDAC inhibition and kinase inhibition, provide synergistic multi-targeted effects against resistance pathways. Antibody-drug conjugates facilitate tumor-selective delivery of HSP90 inhibitors, enabling receptormediated internalization and reducing the impact of efflux mechanisms. Furthermore, nanotechnology-based delivery platforms, including liposomes, polymeric nanoparticles, and stimuli-responsive carriers, enhance pharmacokinetics, enable co-delivery of HSP90 inhibitors with chemotherapeutic agents, and support controlled intratumoral drug release.</p><p><strong>Discussion: </strong>HSP90-targeted strategies represent a promising approach for reversing MDR by simultaneously regulating multiple resistance-associated pathways. The ability of HSP90 inhibitors to disrupt drug efflux transporters, survival signaling networks, and stress adaptation mechanisms provides a strong rationale for their integration with conventional chemotherapy and emerging targeted therapies. However, clinical translation remains challen","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural Polyphenols in Glioblastoma: A Multifaceted Approach to Targeting Tumor Progression.","authors":"Fatima A Jaber","doi":"10.2174/0113895575487049260918062257","DOIUrl":"https://doi.org/10.2174/0113895575487049260918062257","url":null,"abstract":"<p><p>Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults, with a median survival of less than two years despite surgery, radiotherapy, and temozolomide. Its poor outcome reflects diffuse invasion, cellular heterogeneity, and the activation of overlapping pathways (PI3K/AKT/mTOR, Wnt/β-catenin, Notch, and NF-κβ) that sustain growth, therapy resistance, and recurrence. This article reviews evidence that natural polyphenols, especially curcumin, resveratrol, quercetin, and Epigallocatechin Gallate (EGCG), can act as multitarget agents against GBM. Polyphenols promote apoptosis by disrupting mitochondrial potential and regulating caspases; restoring the autophagic balance via AMPK/ULK1 activation and mTOR inhibition; and dampening angiogenesis by reducing HIF-1α and VEGF. They moderate oxidative stress, inhibit NF-κB/STAT3, and remodel the tumor microenvironment by lowering IL-6/TNF-α and Matrix Metalloproteinases (MMP-2/MMP-9), thereby curbing invasion. Epigenetically, they inhibit DNMTs and HDACs and modulate noncoding RNAs, re-expressing tumor-suppressor programs. Importantly, several polyphenols impair glioblastoma stem-like cells by reducing self-renewal, downregulating the expression of stemness markers, and sensitizing cells to temozolomide and radiation. These pleiotropic actions suggest value as adjuncts to current care and in rational combinations with precision approaches. Although these beneficial effects are promising, the efficacy of natural polyphenolic compounds in GBM is limited by their bioavailability and blood‒brain barrier permeability.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in Fc-based Biotherapeutics: Fusion Proteins, Engineering, and Emerging Conjugation Strategies.","authors":"Madison E Gravino, Robert P Doyle","doi":"10.2174/0113895575512514260912092249","DOIUrl":"https://doi.org/10.2174/0113895575512514260912092249","url":null,"abstract":"<p><p>Once considered primarily a structural component of antibodies, the fragment crystallizable (Fc) domain of immunoglobulin G (IgG) has emerged as a versatile platform in modern biotherapeutic design. A principal factor underlying this transition is the interaction of the Fc domain with the neonatal Fc receptor (FcRn), which enables pH-dependent recycling and extends circulation time. This property has made Fc-based approaches especially useful for improving pharmacokinetics. In this mini-review, we examine recent developments in the medicinal chemistry of Fc-fusion proteins and Fc-derived constructs, with particular attention to how structural design influences in vivo behavior. Design features such as linker composition, methods of payload attachment, and Fc glycosylation all play a role in shaping stability, biological activity, and systemic exposure. In addition, strategies to modulate Fc effector function and FcRn binding have made it possible to fine-tune immune engagement while controlling half-life. More recently, Fc-fragmentation approaches have begun to attract attention. These smaller formats can address some of the limitations associated with larger biologics, including restricted tissue penetration and structural complexity, while still retaining useful Fc-mediated properties. Recent clinical examples illustrate a growing interest in tailoring Fc-based designs to specific therapeutic requirements rather than focusing exclusively on half-life extension. Instead of maximizing half-life alone, current designs are tailored to the specific requirements of a given therapeutic context. As a result, the Fc domain is better understood not as a static component, but as a flexible platform that can be adapted to support a range of biologic drug strategies.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Flavonoids as Redox-modulating Therapeutics: Structure-activity Relationships and Nanocarrier Strategies in Medicinal Chemistry.","authors":"Yash Kalra, Shikha Baghel Chauhan, Chirag Jain","doi":"10.2174/0113895575486048260918075608","DOIUrl":"https://doi.org/10.2174/0113895575486048260918075608","url":null,"abstract":"<p><p>Flavonoids are a class of phenolic compounds that display significant antioxidant, antiinflammatory, and cytoprotective activities. Despite their considerable pharmacological activities, flavonoids and their derivatives face significant barriers in their clinical application due to their poor aqueous solubility, rapid first-pass metabolism, and limited inability to traverse biological barriers. Recent progress in the field of nanotechnology has stimulated the design and application of multi-functional nano-carriers for flavonoids, which are tailored to overcome these barriers and maximize flavonoid bioavailability. This review attempts to compile existing knowledge regarding the relationship between flavonoids, bioactivity, and oxidative stress, as well as their bioavailability and the application of modern nanotechnologies. The molecular mechanisms, barriers, and novel nanotechnologies are discussed in detail, including their rationale, parameters, and efficacy in flavonoids' delivery. The application of artificial intelligence in formulation, multi-omics, and in vitro models is also discussed in the context of a novel approach to flavonoids' application and their potential in the treatment and prevention of oxidative stress, neurodegenerative, and inflammatory diseases. This comprehensive review is expected to serve as a significant reference source for those seeking to develop and apply nanotechnology in phytochemical medicine.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Advances and Challenges in Addressing Drug-induced Liver Injury (DILI): Mechanisms and Nanocarrier Solutions.","authors":"Ashok Thulluru, Vrushabh Patil, Chandrapraphu Jangme, Poonam Chougule, Prajakta Pujari","doi":"10.2174/0113895575463249260921063346","DOIUrl":"https://doi.org/10.2174/0113895575463249260921063346","url":null,"abstract":"<p><strong>Introduction: </strong>Drug-Induced Liver Injury (DILI) is a leading cause of drug attrition, postmarketing withdrawals, and acute liver failure. It presents a major barrier to the safe development of new therapeutics, particularly due to its unpredictable pathogenesis and the lack of reliable preclinical models. Current diagnostic tools, primarily reliant on liver enzyme elevations, lack specificity and sensitivity, especially in cases of idiosyncratic DILI. With increasing awareness of these limitations, there is growing interest in integrating advanced delivery systems, predictive models, and pharmacogenomic screening into drug safety assessment.</p><p><strong>Methodology: </strong>This review systematically synthesizes peer-reviewed literature identified through Scopus, PubMed, and Web of Science, published over the past two decades. The review focuses on mechanistic insights into Drug-Induced Liver Injury (DILI), diagnostic challenges, and recent advances in nanocarrier-based drug delivery and predictive strategies. Relevant literature was identified using search terms such as \"DILI,\" \"nanocarriers,\" \"pharmacogenomics,\" and \"liver toxicity.</p><p><strong>Results: </strong>Recent findings underline the complex etiology of DILI, involving mitochondrial dysfunction, reactive metabolite accumulation, and immune-mediated responses. Nanoparticle-based drug formulations, including liposomes, polymeric nanoparticles, and dendritic systems, demonstrate promise in reducing hepatic exposure and delivering hepatoprotective co-agents. Innovations such as liver-on-a-chip models and AI-driven predictive tools offer enhanced screening potential. Pharmacogenomic profiling is increasingly recognized for enabling individualized risk assessment.</p><p><strong>Discussion: </strong>The integration of nanotechnology with predictive toxicology and pharmacogenomics represents a significant advancement in DILI prevention and early detection. These emerging approaches address many limitations of conventional preclinical models by providing more physiologically relevant systems and supporting personalized therapeutic strategies. However, challenges related to clinical translation, regulatory acceptance, cost, and validation across diverse populations remain to be addressed.</p><p><strong>Conclusion: </strong>Advances in nanocarrier-based drug delivery, pharmacogenomics, and human-relevant predictive models have the potential to transform DILI risk assessment and improve drug safety. Continued interdisciplinary research, large-scale clinical validation, and regulatory integration are essential for translating these innovations into routine pharmaceutical development and clinical practice.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phytoalexins as Bioactive Compounds: Structural Diversity, Biosynthesis, and Pharmacological Profile.","authors":"Sonia Singh, Pramod Kumar Singh, Manas Jha","doi":"10.2174/0113895575456084260917065837","DOIUrl":"https://doi.org/10.2174/0113895575456084260917065837","url":null,"abstract":"<p><p>Phytoalexins are low-molecular-weight secondary metabolites with remarkable antibacterial activity, synthesized within the plants in response to abiotic and biotic stimuli. Their structural diversity enables interaction with multiple biological targets, positioning them as promising candidates for nutraceuticals and pharmaceutical research. Preclinical studies have reported antibacterial, anti-diabetic, neurological disorder, antioxidant, anti-inflammatory, and cardiovascular activities. Nonetheless, a few obstacles, including inadequate bioavailability, diversity among botanical sources, and insufficient clinical evidence, remain major challenges for therapeutic translation. Diverse innovative strategies in metabolic engineering, nanodelivery, and biotechnology may improve the synthesis, stability, and therapeutic efficacy of these molecules. Phytoalexins are promising natural molecules that link plant defense mechanisms to potential human health applications, although further clinical validation is required.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Bibliometric Review of Research Trends and Therapeutic Potential Reveals Natural Products as Major Regulators of Mitophagy in Kidney Disease.","authors":"Xu Li, Lan Hu, Qin Hu, Hua Jin","doi":"10.2174/0113895575499846260910074454","DOIUrl":"https://doi.org/10.2174/0113895575499846260910074454","url":null,"abstract":"<p><strong>Objectives: </strong>Kidney disease constitutes a global health burden. Mitophagy, as a critical quality control mechanism, has emerged as an important therapeutic target. This bibliometric analysis systematically reviews global research progress on mitophagy in kidney disease, with particular emphasis on the role of natural products as mitophagy modulators.</p><p><strong>Methods: </strong>Publications were retrieved from the Web of Science Core Collection. Bibliometric and visualization analyses were performed using Bibliometrix, CiteSpace, and VOSviewer software to assess publication trends, major contributors, collaborative networks, and research hotspots.</p><p><strong>Results: </strong>Analysis of 472 articles identified China and the USA as dominant contributors. Keyword analysis identified \"oxidative stress\" and \"apoptosis\" as core themes. Among the reported pharmacological modulators, natural products and their derivatives occupy a predominant position. Representative agents identified include the natural compounds kaempferol, quercetin, esculetin, and dendrobine; the derivatives mitoTEMPO, MitoQ, and CoQ10; and traditional Chinese medicine formulas such as the Baoshentongluo Formula and Huangkui Capsule. These agents primarily regulate mitophagy via the PTEN-Induced Kinase 1 (PINK1)/Parkin pathway, the BCL2 Interacting Protein 3 (BNIP3)/BNIP3-like protein X (NIX) receptor pathway, and the FUN14 Domain-Containing 1 (FUNDC1) receptor pathway, alleviating renal injury by mitigating oxidative stress and inflammation.</p><p><strong>Discussion: </strong>This field is undergoing a transition from basic mechanistic exploration toward therapeutic translation. Natural products are a major source of identified mitophagy regulators; however, challenges remain in the elucidation of active constituents, structural optimization, and preclinical validation. Future research should prioritize addressing these areas to accelerate the progression toward clinical application.</p><p><strong>Conclusion: </strong>This study confirms that natural products represent a rich resource for mitophagy modulation in kidney disease. Advancing structure-activity relationship studies and rigorous preclinical evaluation of these compounds will be essential to develop novel therapeutic strategies.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Green and Metal-free Strategies for Isoxazole Synthesis: A Review of Sonochemical and Organocatalytic Approaches.","authors":"Monika Chauhan, Sumitra Nain","doi":"10.2174/0113895575435613260918072400","DOIUrl":"https://doi.org/10.2174/0113895575435613260918072400","url":null,"abstract":"<p><p>The isoxazole ring is a common moiety in heterocyclic compounds due to its distinctive structural features. Isoxazole is a promising scaffold with diverse biological activities such as anticancer, antibacterial, and anti-inflammatory. Green chemistry synthetic routes aim to reduce hazardous by-products and enhance the applications of isoxazole derivatives in pharmaceutical chemistry. This review covers recent green and metal-free approaches to isoxazole synthesis, emphasizing key methodologies such as sonochemistry, organocatalysis, and other green chemistry strategies. These techniques, notably sonochemistry and organocatalysis, offer operational simplicity, superior atom economy, reduced waste, and improved adherence to green chemistry principles. Additionally, the review assesses limitations seen in metal-catalyzed synthesis-such as high costs, toxicity, limited supply, excessive waste, and difficult separation from products. To address these challenges, current research focuses on developing green, metal-free alternatives that are clean, safe, costeffective, and sustainable. The key benefits of green, metal-free isoxazole synthesis include solventfree reactions, reduced waste, eco-friendliness, cost-effectiveness, rapid reaction times, and high chemo- and regioselectivity under mild conditions. The evolving role of isoxazole in pharmaceutical chemistry underscores its continued importance in drug discovery and development.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"1,2,3-Triazole-Based Hybrids as Emerging Therapeutic Agents: Advances in Drug Design, Computational Studies, and Biological Applications.","authors":"Mausin Khan, Mohammad Ajmal, Nithya Shanthi, Arun Kumar Mahato","doi":"10.2174/0113895575488034260914054438","DOIUrl":"https://doi.org/10.2174/0113895575488034260914054438","url":null,"abstract":"<p><strong>Introduction: </strong>The 1,2,3-triazole scaffold is a privileged heterocyclic motif in medicinal chemistry owing to its chemical stability, click-chemistry accessibility, and broad biological activity. This review examines advances in 1,2,3-triazole-based hybrids, emphasizing antitubercular activity against drug-sensitive and drug-resistant Mycobacterium tuberculosis, as well as applications in cancer, diabetes, and drug-resistant bacterial infections. Attention is given to structure-activity relationships and computational drug-design approaches.</p><p><strong>Methods: </strong>Recent literature on the design, synthesis, biological evaluation, and mechanisms of 1,2,3- triazole hybrids was assessed. Molecular hybridization, biological targets, SAR trends, molecular docking, molecular dynamics simulations, and ADMET analysis were evaluated alongside experimental findings.</p><p><strong>Results: </strong>Triazole hybrids demonstrated activity across all four therapeutic areas. Antitubercular derivatives targeted InhA, DprE1, CYP51, and ATP synthase, whereas anticancer compounds modulated EGFR, VEGFR2, Bcl-2, carbonic anhydrases, and tubulin. Antidiabetic derivatives mainly inhibited α-glucosidase and α-amylase, while antibacterial hybrids targeted DNA gyrase and bacterial ribosomal machinery. Compounds 7, 24, 33, and 37 showed strong activity. Computational studies supported experimental findings by identifying ligand-target interactions and guiding lead optimization.</p><p><strong>Discussion: </strong>SAR analysis indicates that pharmacophore hybridization, electronic and lipophilic substituents, aromatic or fused heterocycles, and hydrogen-bond-forming groups strongly influence biological potency. However, differences in assay conditions and limited correlation between docking scores and experimental activity highlight the need for standardized evaluation.</p><p><strong>Conclusion: </strong>1,2,3-Triazole hybrids represent a versatile platform for drug discovery. Future research should prioritize SAR optimization, target validation, in vivo and pharmacokinetic studies, toxicity assessment, and the integration of artificial intelligence with structure-based design to accelerate the development of therapeutics.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Update (2015-2025) on Synthesis of Anti-inflammatory Pyrimidine Derivatives.","authors":"Kajal Sharma, Kusum, Pankaj Kumar Jain, Sonika Jain","doi":"10.2174/0113895575475582260911075657","DOIUrl":"https://doi.org/10.2174/0113895575475582260911075657","url":null,"abstract":"<p><p>Pyrimidines and their derivatives constitute an important class of six-membered aromatic heterocyclic compounds due to their widespread occurrence in biologically active molecules and their therapeutic and synthetic organic chemistry applications. Pyrimidine derivatives have been found to exhibit numerous biological activities, such as anti-cancer, anti-bacterial, anti-diabetic, anti- inflammatory, anti-viral, anti-oxidant, and anti-fungal. In recent years, increasing attention has been directed toward the development of novel pyrimidine derivatives as potential antiinflammatory agents, driven by the need for safer and more effective alternatives to conventional non-steroidal anti-inflammatory drugs. Recent studies have highlighted their potential as antiinflammatory agents because they can suppress the expression and activity of several key inflammatory mediators. This review discusses recent advances in the synthesis of pyrimidine derivatives and pyrimidine-fused five- and six-membered heterocycles, and their Structure-Activity Relationships (SARs). The synthesis of pyrimidine and fused pyrimidine derivatives from starting materials such as enamines, guanidines, and malonitriles is also discussed, including cyclization, substitution, and cycloaddition reactions, is also discussed. The remarkable synthetic versatility of pyrimidine derivatives further highlights their importance as promising anti-inflammatory agents.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}