RSC medicinal chemistry最新文献_第10页

Design, synthesis, antimicrobial activity, stability, and mechanism of action of bioresorbable ceragenins† 生物可吸收鞣皮素的设计、合成、抗菌活性、稳定性和作用机制。

IF 4.1 4区医学

RSC medicinal chemistry Pub Date : 2025-01-21 DOI: 10.1039/D4MD00990H

Shawn Gubler, Aaron Zaugg, Rebekah Yi, Elliot Sherren, Elizabeth Milner, Wesley Conyer, Tate May, Tim Jack, Tanner Heaton, Joel Christopherson, Preston Higbee, Emma Powers, Meg Takara, Anna Linder, Boston Boyack, Fetutasi Pauga, Morgann Salmon, Miriam Thomas, Mariko Shiraki, Shenglou Deng and Paul B. Savage

{"title":"Design, synthesis, antimicrobial activity, stability, and mechanism of action of bioresorbable ceragenins†","authors":"Shawn Gubler, Aaron Zaugg, Rebekah Yi, Elliot Sherren, Elizabeth Milner, Wesley Conyer, Tate May, Tim Jack, Tanner Heaton, Joel Christopherson, Preston Higbee, Emma Powers, Meg Takara, Anna Linder, Boston Boyack, Fetutasi Pauga, Morgann Salmon, Miriam Thomas, Mariko Shiraki, Shenglou Deng and Paul B. Savage","doi":"10.1039/D4MD00990H","DOIUrl":"10.1039/D4MD00990H","url":null,"abstract":"Device-related infections (DRIs) from bacterial/fungal biofilms that form on surfaces are a major cause of death in first-world countries. DRIs and the increasing prevalence of antibiotic resistant strains require development of new antimicrobials for improved antimicrobial prophylaxis. New antimicrobial prophylaxis practices necessitate novel agents to combat a broad spectrum of both fungi and bacteria, to be less toxic to patients, and to be locally administrable to prevent perturbations to a patient's microbiome. A class of antimicrobials that we have previously developed to fit these criteria is ceragenins. Here we describe the design, synthesis, and characterization of a new series of ceragenins that is composed of and degrades into endogenous compounds: cholic acid, B alanine, and glycerides. From this series we identify an optimized bioresorbable ceragenin that has comparable antimicrobial activities to other ceragenins, degrades rapidly through the action of lipase and at pH 7.2, and has a similar mechanism of action to previously developed ceragenins.","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" 3","pages":" 1425-1440"},"PeriodicalIF":4.1,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080965","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}

引用次数: 0

Nitroaromatic-based triazene prodrugs to target the hypoxic microenvironment in glioblastoma† 硝基芳基三氮杂烯前药靶向胶质母细胞瘤缺氧微环境。

IF 4.1 4区医学

RSC medicinal chemistry Pub Date : 2025-01-20 DOI: 10.1039/D4MD00876F

Cláudia Braga, Margarida Ferreira-Silva, M. Luísa Corvo, Rui Moreira, Alexandra R. Fernandes, João Vaz and Maria J. Perry

{"title":"Nitroaromatic-based triazene prodrugs to target the hypoxic microenvironment in glioblastoma†","authors":"Cláudia Braga, Margarida Ferreira-Silva, M. Luísa Corvo, Rui Moreira, Alexandra R. Fernandes, João Vaz and Maria J. Perry","doi":"10.1039/D4MD00876F","DOIUrl":"10.1039/D4MD00876F","url":null,"abstract":"Hypoxia is a hallmark of the glioblastoma multiforme microenvironment and represents a promising therapeutic target for cancer treatment. Herein, we report nitroaromatic-based triazene prodrugs designed for selective activation by tumoral endogenous reductases and release of the cytotoxic methyldiazonium ion via a self-immolative mechanism. While compounds bearing a 2-nitrofuran bioreductive group were more efficiently activated by nitroreductases, 4-nitrobenzyl prodrugs 1b, 1d and 1e elicited a more pronounced cytotoxic effect against LN-229 and U-87 MG glioblastoma cell lines under hypoxic conditions when compared to temozolomide (TMZ), the golden standard for glioblastoma treatment. This cytotoxic response aligns with the increased apoptosis levels in LN-229 cells and senescence induction in U-87 MG cells, promoted by prodrugs 1d and 1e, under hypoxic conditions. These results highlight the potential of these hypoxia-activated nitroaromatic-based triazene prodrugs for selective delivery of the cytotoxic methyldiazonium ion and support further optimization to provide a safer alternative for glioblastoma treatment.","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" 3","pages":" 1350-1362"},"PeriodicalIF":4.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028875","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}

引用次数: 0

Discovery of a novel pyrimidine derivative for treatment of acute lung injury through reducing oxidative stress and inflammatory response† 发现一种新的嘧啶衍生物，通过减少氧化应激和炎症反应治疗急性肺损伤。

IF 4.1 4区医学

RSC medicinal chemistry Pub Date : 2025-01-18 DOI: 10.1039/D4MD00858H

Yu Jie Jian, Qi Lv, Leran Du, Cen Cen Lei, Li Ping Zhi and Xin Hua Liu

{"title":"Discovery of a novel pyrimidine derivative for treatment of acute lung injury through reducing oxidative stress and inflammatory response†","authors":"Yu Jie Jian, Qi Lv, Leran Du, Cen Cen Lei, Li Ping Zhi and Xin Hua Liu","doi":"10.1039/D4MD00858H","DOIUrl":"10.1039/D4MD00858H","url":null,"abstract":"Acute lung injury (ALI) is a multifactorial respiratory disease characterized by uncontrolled inflammatory response and has high morbidity and mortality. There is currently a lack of effective drugs for ALI treatment. In this study, through nitric oxide (NO) release inhibition and cytotoxicity screening from the in-house compound library, hit compound 6 was discovered. Using 2,4,5-trichloropyrimidine as raw material, 27 new molecules were rapidly synthesized as modified products of compound 6 through nucleophilic substitution reaction and Buchwald–Hartwig reaction. Further activity evaluation and structure–activity relationship study confirmed that compound 32 was a low-toxicity, highly efficient lead compound. Action mechanism studies indicated that compound 32 can significantly reduce the inflammatory response induced by lipopolysaccharide (LPS) in RAW264.7 cells, manifested by the down-regulation of the levels of cytokines, reactive oxygen species (ROS), and the protein expression of Toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) and Kelch-like ECH-associated protein-1/nuclear factor-erythroid 2-related factor 2/heme oxygenase-1 (Keap1-NRF2-HO-1). An in vivo anti-inflammatory study showed that it can reduce the severity of lung injury in the ALI model, accompanied by a reduction in the levels of inflammatory factors and related protein expression levels.","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" 3","pages":" 1441-1458"},"PeriodicalIF":4.1,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143190276","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}

引用次数: 0

Prodrugs and their activation mechanisms for brain drug delivery 前药及其脑给药激活机制。

IF 4.1 4区医学

RSC medicinal chemistry Pub Date : 2025-01-17 DOI: 10.1039/D4MD00788C

Ida Aaberg Lillethorup, Andreas Victor Hemmingsen and Katrine Qvortrup

引用次数: 0

Heterocyclic core modifications in trypanosomacidal 2-[(phenylheteroaryl)ethyl]ureas†‡ 2-[（苯基杂芳基）乙基]脲的杂环核心修饰。

IF 4.1 4区医学

RSC medicinal chemistry Pub Date : 2025-01-15 DOI: 10.1039/D4MD00764F

Arthur Toynton, Lori Ferrins, Harriet L. Newson, Melissa L. Sykes, Swapna Varghese, Nghi Nguyen, Stephanie Russell, Raphaël Rahmani, Jeremy Cheang, Gavin R. Flematti, Brian W. Skelton, Bilal Zulfiqar, Vicky M. Avery, Jonathan B. Baell and Matthew J. Piggott

{"title":"Heterocyclic core modifications in trypanosomacidal 2-[(phenylheteroaryl)ethyl]ureas†‡","authors":"Arthur Toynton, Lori Ferrins, Harriet L. Newson, Melissa L. Sykes, Swapna Varghese, Nghi Nguyen, Stephanie Russell, Raphaël Rahmani, Jeremy Cheang, Gavin R. Flematti, Brian W. Skelton, Bilal Zulfiqar, Vicky M. Avery, Jonathan B. Baell and Matthew J. Piggott","doi":"10.1039/D4MD00764F","DOIUrl":"10.1039/D4MD00764F","url":null,"abstract":"The protozoan parasites Trypanosoma brucei and Trypanosoma cruzi, which cause human African trypanosomiasis (HAT) and Chagas disease, respectively, are responsible for considerable human suffering. Reduced case numbers and improved treatment options for HAT provide hope, but the outlook for Chagas disease is less promising, and safer, more efficacious chemotherapy is sorely needed. We previously reported the discovery and optimisation of a novel class of potent and selective trypanosomacidal 2-[(2-phenylthiazolyl)ethyl]ureas active against both T. brucei brucei and T. cruzi. In the current work, replacement of the core thiazole with alternative heterocycles has revealed that a contiguous arrangement of phenyl substituent, hydrogen-bond-accepting nitrogen, and alkyl linker are required to maintain activity. Compared to the parent thiazole, increased polarity of the core heterocycle in triazoles, tetrazoles and pyrimidines, leads to a drop in potency against T. b. brucei. A 2,6-disubsituted pyridine is tolerated but in general, 5-membered heterocycles are preferred. Analogues with oxazole, pyrazole and isomeric (‘reverse’) pyrazole cores displayed comparable T. b. brucei potency and selectivity to the parent thiazole, and in some cases improved lipophilic ligand efficiencies and metabolic stability. These compounds possessing more polar core heterocycles were generally 2–4 times less potent against T. cruzi (compared to T. b. brucei). This study demonstrates robust structure–activity relationships across a variety of heterocyclic scaffolds, providing many options for further optimisation of this class of compounds.","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" 4","pages":" 1654-1680"},"PeriodicalIF":4.1,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143450133","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}

引用次数: 0

Synthesis and screening of novel 2,4-bis substituted quinazolines as tubulin polymerization promoters and antiproliferative agents† 新型2,4-二取代喹唑啉类微管蛋白聚合促进剂和抗增殖剂的合成与筛选。

IF 4.1 4区医学

RSC medicinal chemistry Pub Date : 2025-01-15 DOI: 10.1039/D4MD00755G

Ashish Ranjan Dwivedi, Vijay Kumar, Vikash Prashar, Kailash Jangid, Naveen Kumar, Bharti Devi, Jyoti Parkash and Vinod Kumar

{"title":"Synthesis and screening of novel 2,4-bis substituted quinazolines as tubulin polymerization promoters and antiproliferative agents†","authors":"Ashish Ranjan Dwivedi, Vijay Kumar, Vikash Prashar, Kailash Jangid, Naveen Kumar, Bharti Devi, Jyoti Parkash and Vinod Kumar","doi":"10.1039/D4MD00755G","DOIUrl":"10.1039/D4MD00755G","url":null,"abstract":"Twelve 2,4-bis-substituted quinazoline-based compounds were synthesized and screened for antiproliferative and tubulin polymerization enhancing potential. In the series, compound A4V-3 substituted with an imidazole ring displayed IC50 values of 4.25 μM, 2.65 μM, and 9.95 μM, and A4V-5 with a benzotriazole substitution displayed IC50 values of 3.45 μM, 7.25 μM, and 8.14 μM against MCF-7, HCT-116 and SHSY-5Y cancer cells, respectively. In the mechanistic studies involving cell cycle analysis, apoptosis assay and JC-1 studies, compound A4V-3 was found to arrest the cells in the G2/M phase of the cell cycle and induce mitochondria-mediated apoptosis. In addition, compound A4V-3 displayed significant tubulin polymerization-enhancing potential. 2,4-Bis-substituted quinazoline-based compounds showed appreciable drug-like characteristics and can be developed as potent anticancer agents.","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" 3","pages":" 1410-1424"},"PeriodicalIF":4.1,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080966","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}

引用次数: 0

Development of small-molecule fluorescent probes targeting neutrophils via N-formyl peptide receptors† 利用n -甲酰基肽受体靶向中性粒细胞的小分子荧光探针的研制。

IF 4.1 4区医学

RSC medicinal chemistry Pub Date : 2025-01-14 DOI: 10.1039/D4MD00849A

Qi Xu, Kalwant S. Authi, Liliya N. Kirpotina, Igor A. Schepetkin, Mark T. Quinn and Agostino Cilibrizzi

{"title":"Development of small-molecule fluorescent probes targeting neutrophils via N-formyl peptide receptors†","authors":"Qi Xu, Kalwant S. Authi, Liliya N. Kirpotina, Igor A. Schepetkin, Mark T. Quinn and Agostino Cilibrizzi","doi":"10.1039/D4MD00849A","DOIUrl":"10.1039/D4MD00849A","url":null,"abstract":" N-Formyl peptide receptors (FPRs) are membrane receptors that are abundantly expressed in innate immune cells, including neutrophils and platelets, demonstrating potential new targets for immune system regulation and the treatment of inflammatory conditions. We report here the development and bio-physical validation of new FPR imaging agents as effective tools to track FPR distribution, localisation and functions, ultimately helping to establish FPR exact roles and functions in pathological and physiological conditions. The new series of probes feature a small molecule-based FPR address system conjugated to suitable fluorophores, resulting in highly specific FPR agents, including a partial agonist endowed with high affinity (i.e. low/sub-nanomolar potency) on FPR-transfected cells and human neutrophils. Preliminary imaging studies via multiphoton microscopy demonstrate that the probes enable the visualisation of FPRs in live cells, thus representing valid bio-imaging tools for the analysis of FPR-mediated signalling, such as the activation of neutrophils in inflammatory events.","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" 3","pages":" 1397-1409"},"PeriodicalIF":4.1,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11775818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067510","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}

引用次数: 0

Novel multipotent conjugate bearing tacrine and donepezil motifs with dual cholinergic inhibition and neuroprotective properties targeting Alzheimer's disease† 具有双重胆碱能抑制和神经保护特性的新型多奈哌齐和他克林多奈哌齐多能偶联物靶向阿尔茨海默病。

IF 4.1 4区医学

RSC medicinal chemistry Pub Date : 2025-01-07 DOI: 10.1039/D4MD00804A

Andrés F. Yepes, Wilson Cardona-Galeano, Angie Herrera-Ramírez, Marlyn S. Rada, Edison Osorio, Luis Alfonso Gonzalez-Molina, Yaneth Miranda-Brand and Rafael Posada-Duque

{"title":"Novel multipotent conjugate bearing tacrine and donepezil motifs with dual cholinergic inhibition and neuroprotective properties targeting Alzheimer's disease†","authors":"Andrés F. Yepes, Wilson Cardona-Galeano, Angie Herrera-Ramírez, Marlyn S. Rada, Edison Osorio, Luis Alfonso Gonzalez-Molina, Yaneth Miranda-Brand and Rafael Posada-Duque","doi":"10.1039/D4MD00804A","DOIUrl":"10.1039/D4MD00804A","url":null,"abstract":"In this work, we developed potential multifunctional agents to combat Alzheimer's disease. According to our strategy, fragments of tacrine and donepezil were merged in a unique hybrid structure. After successfully synthesizing the compounds, they were evaluated for their dual AChE/BuChE inhibitor potential and neuroprotector response using a glutamate-induced excitotoxicity model. Most of the compounds showed promising activity. Among them, the hybrid with 2,5-dimetoxysubstitution (3b) was the most potent analogue, triggering dual potent AChE/BuChE inhibition with low nanomolar affinity (IC50 ∼ 300 nM) and low toxicity to human liver cancer cells (HepG2). This analogue prevented the glutamate excitotoxic stimulus during pre/post treatment testing, maintained ATP levels, possessed an astrocytic protective response, and abolished the glutamate-induced excitotoxicity. Besides, the hit compound 3b exhibited suitable permeability in the blood–brain barrier (BBB) and low degradability in human blood-plasma. In addition, the docking studies suggested that the neuroprotectant response exhibited by 3b can be related to the direct blockage of the NMDA channel pore. Finally, an ideal neuropharmacokinetic profile was estimated for 3b. Overall, the designed conjugates provide a novel multifunctional molecular scaffold that can be used as a prototype drug in further investigations toward novel multipotent therapeutics for treating AD.","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" 3","pages":" 1363-1384"},"PeriodicalIF":4.1,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047337","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}

引用次数: 0

Lazertinib: breaking the mold of third-generation EGFR inhibitors Lazertinib：打破第三代EGFR抑制剂的模式。

IF 4.1 4区医学

RSC medicinal chemistry Pub Date : 2025-01-07 DOI: 10.1039/D4MD00800F

Kishan B. Patel and David E. Heppner

{"title":"Lazertinib: breaking the mold of third-generation EGFR inhibitors","authors":"Kishan B. Patel and David E. Heppner","doi":"10.1039/D4MD00800F","DOIUrl":"10.1039/D4MD00800F","url":null,"abstract":"Small molecules targeting activating mutations within the epidermal growth factor receptor (EGFR) are efficacious anticancer agents, particularly in non-small cell lung cancer (NSCLC). Among these, lazertinib, a third-generation tyrosine kinase inhibitor (TKI), has recently gained FDA approval for use in combination with amivantamab, a dual EGFR/MET-targeting monoclonal antibody. This review delves into the discovery and development of lazertinib underscoring the improvements in medicinal chemistry properties, especially in comparison with osimertinib. Analysis of its structure–activity relationships (SAR), as outlined in the patent literature, reveals the structural diversity explored enroute to the candidate molecule. The resulting structure of lazertinib is distinguished among other TKIs due to the combination of the hydrophobic phenyl and hydrophilic amine substituents on the pyrazole. The structural basis for the selectivity against the T790M mutation is enabled by the substituted pyrazole moiety, which facilitates both van der Waals and H-bonding interactions with the EGFR kinase domain. Insights from this case study offer lessons that can inform the future design of kinase inhibitors with improved safety and efficacy profiles for cancer treatment and other diseases.","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" 3","pages":" 1049-1066"},"PeriodicalIF":4.1,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11758113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047313","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}

引用次数: 0

Synthesis and evaluation of 6-arylaminobenzamides as positron emission tomography imaging ligands for the sphingosine-1-phosphate-5 receptor† 6-芳基氨基苯酰胺作为鞘氨醇-1-磷酸-5受体正电子发射断层成像配体的合成与评价。

IF 4.1 4区医学

RSC medicinal chemistry Pub Date : 2025-01-03 DOI: 10.1039/D4MD00929K

Timaeus E. F. Morgan, Emma K. Grant, Robert C. Shaw, Lachlan J. N. Waddell, Martyn C. Henry, Holly McErlain, Carlos J. Alcaide-Corral, Sally L. Pimlott, Adriana A. S. Tavares and Andrew Sutherland

{"title":"Synthesis and evaluation of 6-arylaminobenzamides as positron emission tomography imaging ligands for the sphingosine-1-phosphate-5 receptor†","authors":"Timaeus E. F. Morgan, Emma K. Grant, Robert C. Shaw, Lachlan J. N. Waddell, Martyn C. Henry, Holly McErlain, Carlos J. Alcaide-Corral, Sally L. Pimlott, Adriana A. S. Tavares and Andrew Sutherland","doi":"10.1039/D4MD00929K","DOIUrl":"10.1039/D4MD00929K","url":null,"abstract":"The sphingosine-1-phosphate-5 (S1P5) receptor is one of the five membrane G protein-coupled receptors that are activated by the lysophospholipid, sphingosine-1-phosphate, resulting in regulation of many cellular processes. S1P5 receptors are located on oligodendrocytes and are proposed to influence oligodendrocyte physiology. Understanding S1P5 modulation during processes such as remyelination could have potential applications for demyelinating CNS disorders such as multiple sclerosis (MS). Herein, we report the synthesis and preliminary evaluation of a series of fluorinated 6-arylaminobenzamides as positron emission tomography (PET) ligands of S1P5. Pharmacokinetic screening and binding evaluation using a [35S]GTPγS assay led to the discovery of TEFM78, a selective and high affinity agonist of S1P5. Radiosynthesis of [18F]TEFM78 allowed pilot PET imaging studies in an animal model, which showed that [18F]TEFM78 can cross the blood brain barrier with good uptake in rat brain and spinal cord.","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" 3","pages":" 1235-1249"},"PeriodicalIF":4.1,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010733","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}

引用次数: 0