Medicinal Chemistry Research最新文献

{"title":"Brepocitinib (Lisraya^®), a first orally administered small molecule dual TYK2/JAK1 inhibitor approved for dermatomyositis in adults.","authors":"Aarajana Shrestha, Tara Man Kadayat","doi":"10.1007/s00044-026-03637-z","DOIUrl":"https://doi.org/10.1007/s00044-026-03637-z","url":null,"abstract":"<p><p>Dermatomyositis is a rare systemic autoimmune disease characterized by chronic inflammation, progressive muscle weakness, and prominent cutaneous manifestations, with limited approved treatment options. Brepocitinib (Lisraya^®), an orally administered dual tyrosine kinase 2 (TYK2) and Janus kinase 1 (JAK1) inhibitor, received the U.S. Food and Drug Administration approval on August 27, 2026, for the treatment of dermatomyositis in adults. Unlike broader JAK inhibitors, brepocitinib exhibits preferential activity against JAK1 and TYK2 over JAK2 and JAK3, providing a differentiated kinase-selectivity profile. In the phase 3 VALOR trial, once-daily brepocitinib 30 mg significantly improved the Total Improvement Score and multiple measures of dermatomyositis disease activity compared with placebo. Its approval highlights the successful application of kinase-directed medicinal chemistry to a rare autoimmune disease and provides a new oral therapeutic option for adults with dermatomyositis. Brepectinib molecule structure is shown inhibiting two proteins labeled TYK2 and JAK1, with red bars indicating TYK2 and JAK1 inhibition.</p>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149340251","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":"Zidebactam as a new approved β-Lactamase inhibitor with intrinsic antibacterial activity via PBP2 binding.","authors":"Marco Pieroni","doi":"10.1007/s00044-026-03636-0","DOIUrl":"https://doi.org/10.1007/s00044-026-03636-0","url":null,"abstract":"<p><p>Antimicrobial resistance continues to challenge the clinical efficacy of established antibiotics, highlighting the need for innovative therapeutic strategies. Cefepime/zidebactam combines a fourth-generation cephalosporin with a novel diazabicyclooctane β-lactamase inhibitor endowed with intrinsic PBP2-targeting activity. This commentary discusses the pharmacology, mechanism of action, and medicinal chemistry of zidebactam, focusing on its distinctive peculiarities. Complementary PBP2/PBP3 targeting, together with serine β-lactamase inhibition, provides a multifaceted strategy to restore and enhance β-lactam activity against resistant pathogens. The chemical structure highlights two key functional groups: an acyl-hydrazide-derived side chain ending in a piperidine ring, which enables recognition of PBP2, and a DBO nucleus containing a urea group that reacts with the active site serine residue in beta-lactamases.</p>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149316890","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":"Remibrutinib (Rhapsido^®), a covalent Bruton's tyrosine kinase inhibitor approved for chronic spontaneous urticaria.","authors":"Abdusemi Abduweli, Longqin Hu","doi":"10.1007/s00044-026-03634-2","DOIUrl":"https://doi.org/10.1007/s00044-026-03634-2","url":null,"abstract":"<p><p>Remibrutinib (Rhapsido^®) is a selective, orally bioavailable covalent inhibitor of Bruton's tyrosine kinase (BTK), approved in 2025 for the treatment of adult chronic spontaneous urticaria (CSU) uncontrolled by H₁-antihistamines. By blocking BTK, it suppresses signaling pathways driving mast cell, basophil, and B-cell activation in immune-mediated disease. This review traces remibrutinib's journey from target validation to market approval, detailing the structure-activity relationships that optimized early CGI-560 and CGI-1746 scaffolds into pyrrolopyrimidine and 6-aminopyrimidine series, as well as the process chemistry redesign for commercial synthesis. By covalently capturing BTK in its inactive conformation, remibrutinib achieves exceptional kinase selectivity. This translates into rapid symptom control, convenient oral administration as an alternative to injectable biologics, and a favorable safety profile where mild mucocutaneous bleeding is the primary mechanism-based risk. Remibrutinib is also in late-stage development for other chronic, non-lethal inflammatory conditions including chronic inducible urticaria, hidradenitis suppurativa, Sjögren disease, and multiple sclerosis. Two-panel molecular graphic of the BTK kinase domain in complex with remibrutinib (PDB: 6TFP). The left panel shows a ribbon diagram of the protein. The smaller N-terminal lobe, built around a β-sheet, is coloured yellow. The larger C-terminal lobe, composed mainly of α-helices, is coloured blue. The hinge region, which connects the two lobes, is highlighted in purple. Remibrutinib is drawn as green space-filling spheres, with blue nitrogen, red oxygen and pale cyan fluorine atoms, and sits in the ATP-binding cleft between the two lobes, adjacent to the hinge. The residue Cys481, shown with a gold sulfur atom, lies directly beside the inhibitor, and Tyr551 is labelled on the right.The right panel is an enlarged view of the boxed region, joined to the left panel by red dashed lines. The inhibitor (labelled REMI701) is drawn as green sticks, and the surrounding residues are drawn as thin lines: Leu408, Lys430, Gln412, Tyr551, Met477, Leu528 and Cys481. Dotted lines mark hydrogen bonds between the inhibitor and the backbone of Met477 in the hinge region, the Cys481 residue, and nearby residues such as Gln412.</p>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149316889","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":"Camizestrant (Etcamah^®): an oral estrogen receptor degrader and estrogen receptor antagonist approved for breast cancer.","authors":"Daniel Baecker","doi":"10.1007/s00044-026-03633-3","DOIUrl":"https://doi.org/10.1007/s00044-026-03633-3","url":null,"abstract":"<p><p>Hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative tumors are the most common types of breast cancer. Mutation of ESR1 complicates their therapy. On September 04, 2026, camizestrant (Etcamah^®) received approval for HR-positive and HER2-negative, locally advanced or metastatic breast cancer after detecting ESR1 mutation during medication with aromatase and CDK4/6 inhibitors. The mutation was identified through circulating tumor deoxyribonucleic acid, thus representing its first interventional use to guide a therapy switch as part of a clinical study. Camizestrant is a selective estrogen receptor degrader (SERD) and complete antagonist of the estrogen receptor. A dose of 75 mg is taken by mouth once daily concomitantly with a cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor. In a drug regimen comprising an aromatase inhibitor along with a CDK4/6 inhibitor, a significant improvement in progression-free survival was achieved when the aromatase inhibitor was exchanged for camizestrant. This makes camizestrant a next-generation oral SERD for treating advanced breast cancer. The image identifies three chemical groups within the camizestrant molecule and associates each with a specific functional role: one group controls the degradation profile, another regulates basicity and lipophilicity, and a third influences solubility and protein binding. Additionally, the image includes a pink ribbon labeled with the breast cancer classifications ESR1, HR-positive, and HER2-negative.</p>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149316888","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":"Small-molecule ferroptosis inducers and sensitizers in anticancer drug discovery: medicinal chemistry, structure-activity relationships, and translational perspectives.","authors":"Aashik Malik, Md Arif Naseer, Mayank Yadav, Zulphikar Ali, Jai Parkash Kadian","doi":"10.1007/s00044-026-03632-4","DOIUrl":"https://doi.org/10.1007/s00044-026-03632-4","url":null,"abstract":"<p><p>Ferroptosis, an iron-dependent form of regulated cell death driven by phospholipid peroxidation, proceeds independently of caspase activation and can remain effective in apoptosis-resistant and mesenchymal-like tumor populations, providing a pharmacologically addressable route around treatment resistance. Its regulation by enzymes, transporters and metabolic pathways, including glutathione peroxidase 4 (GPX4), the cystine/glutamate antiporter system xc⁻, ferroptosis suppressor protein 1 (FSP1), mitochondrial dihydroorotate dehydrogenase (DHODH), and iron and lipid metabolism, has created multiple starting points for small-molecule design. Unlike prior target-by-target surveys, this review cross-examines structure-activity relationships across these target classes to distinguish transferable design principles from mechanism-specific effects, and chemical probes from pharmacologically viable leads. Cross-target analysis shows that no single SAR pattern governs ferroptosis induction: scaffold requirements are target-dependent, linker length and rigidity produce mechanism-dependent effects, and electrophilic warheads require calibrated rather than maximal reactivity. Substituent modifications that improve one chemotype do not reliably transfer to another, while hybrid and multi-target compounds require evidence for target-specific contributions to activity. Translational evaluation reveals a recurring gap between cellular potency and the solubility, metabolic stability, systemic exposure, in vivo efficacy and tolerability required for development. Most compounds remain chemical probes, with PK/ADMET characterization, therapeutic-window data, off-target control and validated biomarkers for patient selection frequently lacking. Progress will therefore depend less on increasing ferroptotic potency than on converting active chemotypes into target-selective, pharmacokinetically viable and tolerable agents for biomarker-defined patient populations. Graphical abstract illustrating key druggable targets in ferroptosis, including GPX4, System Xc⁻, FSP1, DHODH, and iron/lipid metabolism, and the drug-development pathway from chemical probe discovery and SAR optimization to lead development, evaluation of translational limitations, and biomarker-guided translation.</p>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149260349","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":"Azole chroman-4-one, tetralone and chromen-4-one derivatives: synthesis, Mycobacterium tuberculosis CYP121A1 enzyme inhibition and antimycobacterial activity.","authors":"Jabril M Abdali, Lama A Alshabani, Alistair K Brown, Amit Kumar, Sam Wilcocks, Ahmed Y G Alhejaili, Sanjida Y Kalam, D Fernando Estrada, Claire Simons","doi":"10.1007/s00044-026-03631-5","DOIUrl":"https://doi.org/10.1007/s00044-026-03631-5","url":null,"abstract":"<p><p>Tuberculosis (TB) remains a major global health challenge, driven by the emergence of drug-resistant Mycobacterium tuberculosis (Mtb) strains and the limitations of existing treatment regimens. Twenty CYP enzymes unique to Mtb represent an underexploited class of targets, offering opportunities for selective inhibition. Among these, CYP121A1 enzyme has been identified as a promising target. Three series of azole derivatives employing either a chroman-4-one, tetralone or chromen-4-one pharmacophore were synthesised and evaluated against Mtb CYP121A1 (binding affinity, K_D) and against wild type and resistant Mtb strains. From these three series, the tetralones with a propyloxy linked to a 4-F (6g) and 4-Cl (6h) benzene ring showed the most promising activity overall considering binding affinity (CYP121A1 K_D6g 0.18 ± 0.1 μM; 6h 0.22 ± 0.12 μM, cf. cYY 12.3 ± 1.1 μM) and antimycobacterial activity against wild-type H37Rv strain (MIC 6g 12.5 μM, 2.7 μg/mL; 6h 6 μM. 2.4 μg/mL) and mc²7902 triple auxotrophic drug susceptible strain (MIC 6g 2.6 μM, 1 μg/mL; 6h 2.5 μM. 1 μg/mL) comparable with ethambutol and ethionamide. Importantly, the choman-4-one and tetralone derivatives all retained antimycobacterial activity against isoniazid (INH), rifampicin (RIF) and INH + RIF resistant strains. Tetralone derivative 6h and chromen-4-one 12c displayed mycobacteriostatic properties and both compounds displayed favourable SI values in A459 cells and macrophages with the tetralone 6h showing an improved therapeutic window with SI > 10. Type II direct CYP121A1 binding was generally supported by computational studies with all compounds near the haem. Generally, correlation was observed between binding affinity and antimycobacterial activity. The image compares two chemical compounds, labeled 6h and 12c, with their molecular structures and binding affinities to Mtb CYP121A1 enzyme. Compound 6h has a dissociation constant of 0.22 micromolar, while 12c has 0.52 micromolar. Below each compound, a table lists minimum inhibitory concentrations (MIC) against different Mycobacterium tuberculosis strains. For 6h, MIC values are 6 micromolar for wild type H37Rv, 2.5 micromolar for drug sensitive mc27902, and 2.5 micromolar for multidrug resistant mc8250. For 12c, MIC values are higher: 25 micromolar for wild type H37Rv, 8.5 micromolar for drug sensitive mc27902, and 6.5 micromolar for multidrug resistant mc8250. The data show that compound 6h has lower MIC values across all strains compared to 12c.</p>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149242401","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":"Structure-based discovery of acridone alkaloids as disruptors of the HEG1-KRIT1 protein-protein interaction in cerebral cavernous malformation signaling.","authors":"Emadeldin M Kamel, May Bin-Jumah, Haifa E Alfassam, Raghad A Alotaibi, Ahmed A Allam, Fahad M Alshabrmi, Faris F Aba Alkhayl, Al Mokhtar Lamsabhi","doi":"10.1007/s00044-026-03627-1","DOIUrl":"https://doi.org/10.1007/s00044-026-03627-1","url":null,"abstract":"<p><p>The HEG1-KRIT1 interaction is essential for endothelial cerebral cavernous malformation complex localization and signaling, making this interface a relevant target for chemical disruption. This study aimed to identify acridone alkaloids capable of inhibiting HEG1 binding to KRIT1 through integrated virtual screening, molecular simulations, binding-energy analysis, drug-likeness prediction, and experimental validation. Screening of 2,449 acridone alkaloids prioritized five candidates: 5-hydroxynoracronycine, acronycine, arborinine, glycocitrine I, and rutacridone. Computational analyses showed stable binding within the HEG1-recognition pocket of KRIT1 and predicted interface weakening, with rutacridone and 5-hydroxynoracronycine producing the strongest destabilizing effects. A bead-based flow-cytometry competition assay confirmed concentration-dependent inhibition, with half-maximal inhibitory concentration values of 2.21 ± 0.31 µM for rutacridone, 2.30 ± 0.30 µM for arborinine, and 2.90 ± 0.35 µM for 5-hydroxynoracronycine. These findings identify rutacridone, arborinine, and 5-hydroxynoracronycine as promising acridone-based starting points for developing HEG1-KRIT1 interaction disruptors. The image explains the difference between normal and disrupted HEG1-KRIT1 protein interactions affecting CCM signaling. On the left, the homeostatic HEG1-KRIT1 complex forms at the endothelial cell membrane, where HEG1 and VE-cadherin proteins connect with KRIT1 (FERM domain) and CCM2 and CCM3 proteins. This complex activates a signaling cascade through MEKK3, MEK5, ERK5, MEF2, and KLF2/4, resulting in regulated CCM signaling. On the right, a small-molecule protein-protein interaction disruptor blocks the binding between HEG1 and KRIT1, shown by a red cross. This disruption prevents the normal complex formation, leading to dysregulated CCM signaling and an altered KLF2/4 transcriptional response. A predicted binding model illustrates the small molecule at the HEG1-KRIT1 interface, with HEG1 cytoplasmic tail and KRIT1 FERM domain labeled.</p>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178653","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":"Coumarin scaffolds in breast cancer research: derivatives, hybrids, and therapeutic potential.","authors":"Shagufta, Irshad Ahmad, Isha Khan, Maimonah Al Zubaidi, Aayat Aladhamy","doi":"10.1007/s00044-026-03629-z","DOIUrl":"https://doi.org/10.1007/s00044-026-03629-z","url":null,"abstract":"<p><p>Breast cancer remains one of the most common cancers worldwide and continues to present major therapeutic challenges due to tumor diversity, drug resistance, and recurrence. These issues highlight the need for new treatments with better selectivity and multitarget effects. Coumarins, a class of naturally occurring benzopyran-2-one derivatives, have attracted significant interest in medicinal chemistry because of their structural flexibility, favorable drug-like properties, and broad range of biological activities. The coumarin scaffold offers several chemically accessible sites for extensive structural modification, facilitating the development of derivatives and hybrid molecules with improved pharmacological profiles. This review covers recent advances in developing coumarin-based derivatives and hybrid compounds as potential agents for breast cancer treatment. Overall, coumarin scaffolds remain promising platforms for designing multitarget anticancer agents and continue to offer valuable opportunities for creating new therapeutic strategies against breast cancer. This diagram presents coumarin as a central chemical structure with two categories of related compounds: derivatives and hybrid molecules. Derivatives are associated with potent anticancer activity, structural diversity, and multiple mechanisms. Hybrid molecules are linked to molecular hybridization, enhanced efficacy, and broad therapeutic potential. Both categories are connected to an effect on breast cancer cells.</p>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178676","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":"Special issue of Medicinal Chemistry Research in honor of Dr. Kenneth A. Jacobson","authors":"Carola Gallo-Rodriguez,&nbsp;Juan Bautista Rodriguez,&nbsp;Pnina Fishman","doi":"10.1007/s00044-026-03630-6","DOIUrl":"10.1007/s00044-026-03630-6","url":null,"abstract":"","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"35 10","pages":"1819 - 1820"},"PeriodicalIF":3.5,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00044-026-03630-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149147148","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":"Bicyclononane-2,8-bis(trifluoromethyl)quinoline hybrids: synthesis, antiplasmodial and antitrypanosomal activity.","authors":"Johanna Dolensky, Werner Seebacher, Eva-Maria Pferschy-Wenzig, Miriam Zehentner, Robert Saf, Pascal Mäser, Monica Cal, Robert Weis","doi":"10.1007/s00044-026-03628-0","DOIUrl":"https://doi.org/10.1007/s00044-026-03628-0","url":null,"abstract":"<p><p>With the aim to design dual-acting antiprotozoals, a set of hybrid-molecules was prepared. Amino-substituted 2-aza- and 3-azabicyclo[3.2.2]nonanes with antiplasmodial and antitrypanosomal activity were linked via aminoalkyl linkers to the 2,8-bis(trifluoromethyl)quinoline scaffold of mefloquine. All newly synthesized compounds were characterized by IR spectroscopy, NMR spectroscopy, and HRMS. Their antiplasmodial activities were examined in vitro against the NF54 strain of Plasmodium falciparum and their antitrypanosomal activity against the STIB900 strain of Trypanosoma brucei rhodesiense. Most of the compounds showed antiprotozoal activity in submicromolar concentration. Structure-activity relationships concerning the linker length as well as the amino substituent and ring position of the nitrogen in the bicyclic ring system were discussed. The most promising of the newly synthesized compounds was a 2-azabicyclononane with an aminopropyl linker and a 4-methylpiperazinyl substituent at a bridgehead atom. It showed excellent antiplasmodial and antitrypanosomal activity (IC₅₀ ≤ 0.065 µM). Two chemical compounds labeled 8d and 9c are shown with their molecular structures and activity data. Compound 8d has a half-maximal inhibitory concentration (IC50) of 0.050 micromolar against P.f NF54, 0.065 micromolar against T. b. r., and 2.860 micromolar cytotoxicity in L6 cells. Compound 9c has an IC50 of 0.051 micromolar against P.f. NF54, 0.537 micromolar against T. b. r., and 1.845 micromolar cytotoxicity in L6 cells. The structures share a common core with variations in the nitrogen-containing ring and side chains.</p>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102576","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}