首页 > 最新文献

Journal of Medicinal Chemistry最新文献

英文 中文
Drug Repurposing: Conversion of the Peripherally Restricted HIV Protease Inhibitor Amprenavir to Potent, Selective, and CNS-Penetrant Agonists for the Cannabinoid Receptor 2 药物再利用:将外周限制性HIV蛋白酶抑制剂Amprenavir转化为大麻素受体2的强效、选择性和cns渗透激动剂
IF 7.3 1区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2026-02-05 DOI: 10.1021/acs.jmedchem.5c02796
Daniel H. Haymer, Renn A. Duncan, Alice L. Rodriguez, Allie Han, Richard J. Lindsay, N. Kithmini Wijesiri, Analisa Thompson Gray, Srinivasan Krishnan, Aidong Qi, Benjamin P. Brown, Olivier Boutaud, Darren W. Engers, Carrie K. Jones, Colleen M. Niswender, Craig W. Lindsley, Aaron M. Bender
Herein, we report the identification of the HIV protease inhibitor amprenavir as a selective cannabinoid receptor 2 (CB2) agonist and describe structure–activity relationship (SAR) studies toward repurposing this peripherally restricted scaffold for high CB2 potency and CNS exposure. This exercise yielded compounds with exceptional CB2 potency (EC50s <10 nM), no appreciable activity at the CB1 receptor, and high predicted permeability/low P-gp efflux activity. Selected compounds were profiled in rat i.v. dosing cassettes; several novel amprenavir analogues displayed good t1/2 (>2 h), moderate plasma clearance, and appreciable brain exposure. Additionally, fully flexible protein–ligand docking studies with molecular dynamics (MD) simulations were used to predict the most likely mode of interaction of highly potent analogue VU6077967 with CB2 and to provide a rationale for the observed selectivity of this series relative to CB1.
在此,我们报告了HIV蛋白酶抑制剂amprenavir作为选择性大麻素受体2 (CB2)激动剂的鉴定,并描述了结构-活性关系(SAR)研究,以重新利用这种外周限制性支架来实现高CB2效力和中枢神经系统暴露。该实验产生的化合物具有特殊的CB2效力(ec50 <10 nM),对CB1受体没有明显的活性,预测渗透率高/ P-gp外排活性低。选定的化合物在大鼠静脉给药盒中进行了谱图分析;几种新型安非那韦类似物表现出良好的t1/2 (> 2h),中度血浆清除率和明显的脑暴露。此外,利用分子动力学(MD)模拟的全柔性蛋白配体对接研究,预测了高效类似物VU6077967与CB2最可能的相互作用模式,并为该系列相对于CB1的选择性提供了理论依据。
{"title":"Drug Repurposing: Conversion of the Peripherally Restricted HIV Protease Inhibitor Amprenavir to Potent, Selective, and CNS-Penetrant Agonists for the Cannabinoid Receptor 2","authors":"Daniel H. Haymer, Renn A. Duncan, Alice L. Rodriguez, Allie Han, Richard J. Lindsay, N. Kithmini Wijesiri, Analisa Thompson Gray, Srinivasan Krishnan, Aidong Qi, Benjamin P. Brown, Olivier Boutaud, Darren W. Engers, Carrie K. Jones, Colleen M. Niswender, Craig W. Lindsley, Aaron M. Bender","doi":"10.1021/acs.jmedchem.5c02796","DOIUrl":"https://doi.org/10.1021/acs.jmedchem.5c02796","url":null,"abstract":"Herein, we report the identification of the HIV protease inhibitor amprenavir as a selective cannabinoid receptor 2 (CB<sub>2</sub>) agonist and describe structure–activity relationship (SAR) studies toward repurposing this peripherally restricted scaffold for high CB<sub>2</sub> potency and CNS exposure. This exercise yielded compounds with exceptional CB<sub>2</sub> potency (EC<sub>50</sub>s &lt;10 nM), no appreciable activity at the CB<sub>1</sub> receptor, and high predicted permeability/low P-gp efflux activity. Selected compounds were profiled in rat i.v. dosing cassettes; several novel amprenavir analogues displayed good <i>t</i><sub>1/2</sub> (&gt;2 h), moderate plasma clearance, and appreciable brain exposure. Additionally, fully flexible protein–ligand docking studies with molecular dynamics (MD) simulations were used to predict the most likely mode of interaction of highly potent analogue VU6077967 with CB<sub>2</sub> and to provide a rationale for the observed selectivity of this series relative to CB<sub>1</sub>.","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":"9 1","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146116009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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, Synthesis, and Biological Evaluation of Novel Quinoline-Based PDE4 Inhibitors with Potent Anti-Chronic Obstructive Pulmonary Disease Activity 具有有效抗慢性阻塞性肺疾病活性的新型喹啉类PDE4抑制剂的发现、合成和生物学评价
IF 7.3 1区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2026-02-05 DOI: 10.1021/acs.jmedchem.5c02775
Gang Xing, Yucong Bi, Zhenli Li, Zhengxing Zhi, Haitao Li, Maosheng Cheng
Phosphodiesterase 4 (PDE4) is a key target for COPD anti-inflammatory drugs. The approved oral PDE4 inhibitor for COPD causes side effects such as nausea and vomiting due to high systemic exposure. Developing highly selective PDE4 inhibitors suitable for inhaled delivery represents an effective alternative strategy. Herein, we report the identification of P29, a PDE4 inhibitor exhibiting picomolar inhibitory potency (IC50 = 0.019 nM) and high selectivity (>10,000) over other PDEs. Subsequent studies demonstrated that P29 effectively suppressed LPS-induced TNF-α release in PBMCs. Notably, the fractions absorbed via pulmonary deposition and orally absorbed fractions were rapidly metabolized, reducing systemic exposure and minimizing adverse reactions. P29 significantly improved pulmonary function, inhibited inflammatory cell activity, reduced release of inflammatory cytokines, and ameliorated lung tissue damage in rat models of COPD induced by cigarette smoke and LPS. Collectively, our data highlight the therapeutic potential of P29 in COPD.
磷酸二酯酶4 (PDE4)是COPD抗炎药物的关键靶点。经批准的用于慢性阻塞性肺病的口服PDE4抑制剂由于高系统性暴露导致恶心和呕吐等副作用。开发适合吸入给药的高选择性PDE4抑制剂是一种有效的替代策略。在此,我们报告了P29的鉴定,P29是一种PDE4抑制剂,具有皮摩尔抑制效力(IC50 = 0.019 nM)和高选择性(>10,000)。随后的研究表明,P29可有效抑制lps诱导的pbmc中TNF-α的释放。值得注意的是,通过肺沉积吸收的部分和口服吸收的部分被迅速代谢,减少了全身暴露,最大限度地减少了不良反应。在香烟烟雾和LPS诱导的COPD大鼠模型中,P29可显著改善肺功能,抑制炎症细胞活性,减少炎症细胞因子的释放,改善肺组织损伤。总的来说,我们的数据强调了P29在COPD中的治疗潜力。
{"title":"Discovery, Synthesis, and Biological Evaluation of Novel Quinoline-Based PDE4 Inhibitors with Potent Anti-Chronic Obstructive Pulmonary Disease Activity","authors":"Gang Xing, Yucong Bi, Zhenli Li, Zhengxing Zhi, Haitao Li, Maosheng Cheng","doi":"10.1021/acs.jmedchem.5c02775","DOIUrl":"https://doi.org/10.1021/acs.jmedchem.5c02775","url":null,"abstract":"Phosphodiesterase 4 (PDE4) is a key target for COPD anti-inflammatory drugs. The approved oral PDE4 inhibitor for COPD causes side effects such as nausea and vomiting due to high systemic exposure. Developing highly selective PDE4 inhibitors suitable for inhaled delivery represents an effective alternative strategy. Herein, we report the identification of P29, a PDE4 inhibitor exhibiting picomolar inhibitory potency (IC<sub>50</sub> = 0.019 nM) and high selectivity (&gt;10,000) over other PDEs. Subsequent studies demonstrated that P29 effectively suppressed LPS-induced TNF-α release in PBMCs. Notably, the fractions absorbed via pulmonary deposition and orally absorbed fractions were rapidly metabolized, reducing systemic exposure and minimizing adverse reactions. P29 significantly improved pulmonary function, inhibited inflammatory cell activity, reduced release of inflammatory cytokines, and ameliorated lung tissue damage in rat models of COPD induced by cigarette smoke and LPS. Collectively, our data highlight the therapeutic potential of P29 in COPD.","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":"30 1","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146122292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Cyclic Diguanylate G-Quadruplex Inducer–Siderophore Hybrids as Bifunctional Antibiofilm Agents against Pseudomonas aeruginosa 环双胍酯g -四重诱导剂-铁载体杂种作为铜绿假单胞菌双功能抗菌膜剂
IF 7.3 1区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2026-02-04 DOI: 10.1021/acs.jmedchem.5c02948
Ye-Si Huang,Jing Liu,Mei-Yan Huang,Yu-Jing Wang,Wei-Min Chen,Jing Lin
Biofilm formation is a crucial determinant of both pathogenicity and enhanced antibiotic resistance in Pseudomonas aeruginosa. Sustainable iron utilization in the bacterial growth environments and intracellular c-di-GMP signaling molecules are key factors promoting bacterial biofilm development. Capitalizing on our previous findings that c-di-GMP G-quadruplex inducers exhibit potent antibiofilm activity and that 3-hydroxypyridin-4(1H)-ones act as effective iron chelators, we designed and synthesized dual-functional hybrid molecules incorporating both pharmacophores. The lead compound 11f, which features a benzothiazole-pyridinone scaffold, demonstrated potent biofilm inhibition against both wild-type P. aeruginosa PAO1 and the hyper-biofilm-forming PAO1-ΔwspF mutant. Mechanistic investigations revealed that 11f operates through dual pathways: facilitating c-di-GMP G-quadruplex formation and disrupting iron acquisition systems. Notably, in Galleria mellonella infection models, 11f exhibited significant synergistic effects with ciprofloxacin and tobramycin while maintaining an excellent safety profile, highlighting its potential as an antibacterial adjuvant.
生物膜的形成是铜绿假单胞菌致病性和增强抗生素耐药性的关键决定因素。细菌生长环境中铁的可持续利用和细胞内c-di-GMP信号分子是促进细菌生物膜发育的关键因素。利用我们之前的发现,c-二- gmp g -四重诱导剂具有有效的抗生物膜活性,3-羟基吡啶-4(1H)- 1作为有效的铁螯合剂,我们设计并合成了包含两种药效团的双功能杂交分子。先导化合物11f具有苯并噻唑-吡啶酮支架,对野生型铜绿假单胞菌PAO1和超生物膜形成PAO1-ΔwspF突变体均有有效的生物膜抑制作用。机制研究表明11f通过双重途径起作用:促进c-二- gmp g -四联体形成和破坏铁获取系统。值得注意的是,在mellonella Galleria感染模型中,11f与环丙沙星和妥布霉素表现出显著的协同效应,同时保持良好的安全性,突出了其作为抗菌佐剂的潜力。
{"title":"Cyclic Diguanylate G-Quadruplex Inducer–Siderophore Hybrids as Bifunctional Antibiofilm Agents against Pseudomonas aeruginosa","authors":"Ye-Si Huang,Jing Liu,Mei-Yan Huang,Yu-Jing Wang,Wei-Min Chen,Jing Lin","doi":"10.1021/acs.jmedchem.5c02948","DOIUrl":"https://doi.org/10.1021/acs.jmedchem.5c02948","url":null,"abstract":"Biofilm formation is a crucial determinant of both pathogenicity and enhanced antibiotic resistance in Pseudomonas aeruginosa. Sustainable iron utilization in the bacterial growth environments and intracellular c-di-GMP signaling molecules are key factors promoting bacterial biofilm development. Capitalizing on our previous findings that c-di-GMP G-quadruplex inducers exhibit potent antibiofilm activity and that 3-hydroxypyridin-4(1H)-ones act as effective iron chelators, we designed and synthesized dual-functional hybrid molecules incorporating both pharmacophores. The lead compound 11f, which features a benzothiazole-pyridinone scaffold, demonstrated potent biofilm inhibition against both wild-type P. aeruginosa PAO1 and the hyper-biofilm-forming PAO1-ΔwspF mutant. Mechanistic investigations revealed that 11f operates through dual pathways: facilitating c-di-GMP G-quadruplex formation and disrupting iron acquisition systems. Notably, in Galleria mellonella infection models, 11f exhibited significant synergistic effects with ciprofloxacin and tobramycin while maintaining an excellent safety profile, highlighting its potential as an antibacterial adjuvant.","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":"30 1","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146111158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 Novel, Potent, and Selective IRAK1 Inhibitors as Potential Therapeutics for Hepatocellular Carcinoma 发现新的、有效的、选择性的IRAK1抑制剂作为肝细胞癌的潜在治疗药物
IF 7.3 1区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2026-02-04 DOI: 10.1021/acs.jmedchem.5c02988
Wenjian Min,Junfeng He,Qiman Zhang,Chunling Chen,Yanyin Wang,Yuanyuan Chen,Yunchu Zhao,Yi Hou,Chengliang Sun,Xiao Wang,Kai Yuan,Yasheng Zhu,Peng Yang
Interleukin-1 receptor-associated kinase 1 (IRAK1) is a critical mediator of Toll-like receptor (TLR)/interleukin-1 receptor (IL-1R) signaling, and its aberrant activation is implicated in the pathogenesis of various cancers, including hepatocellular carcinoma (HCC). However, the development of clinical IRAK1 inhibitors has been hampered by a lack of sufficient selectivity over other kinases. Herein, we report the discovery of a novel IRAK1 inhibitor, A34, identified through structure-based virtual screening and structural optimization. A34 potently inhibited IRAK1 with an IC50 value of 10.6 nM and demonstrated exceptional selectivity over 215 other kinases, notably including IRAK4. Furthermore, A34 demonstrated significant anti-HCC activity both in vivo and in vitro, making it a valuable chemical probe for IRAK1 and a potential lead candidate for the treatment of HCC.
白细胞介素-1受体相关激酶1 (IRAK1)是toll样受体(TLR)/白细胞介素-1受体(IL-1R)信号传导的重要介质,其异常激活与包括肝细胞癌(HCC)在内的多种癌症的发病有关。然而,临床IRAK1抑制剂的开发一直受到其他激酶缺乏足够选择性的阻碍。在此,我们报告了一种新的IRAK1抑制剂A34的发现,通过基于结构的虚拟筛选和结构优化鉴定。A34有效抑制IRAK1, IC50值为10.6 nM,并对其他215种激酶(特别是IRAK4)表现出卓越的选择性。此外,A34在体内和体外均表现出显著的抗HCC活性,使其成为一种有价值的IRAK1化学探针,也是治疗HCC的潜在先导候选物。
{"title":"Discovery of Novel, Potent, and Selective IRAK1 Inhibitors as Potential Therapeutics for Hepatocellular Carcinoma","authors":"Wenjian Min,Junfeng He,Qiman Zhang,Chunling Chen,Yanyin Wang,Yuanyuan Chen,Yunchu Zhao,Yi Hou,Chengliang Sun,Xiao Wang,Kai Yuan,Yasheng Zhu,Peng Yang","doi":"10.1021/acs.jmedchem.5c02988","DOIUrl":"https://doi.org/10.1021/acs.jmedchem.5c02988","url":null,"abstract":"Interleukin-1 receptor-associated kinase 1 (IRAK1) is a critical mediator of Toll-like receptor (TLR)/interleukin-1 receptor (IL-1R) signaling, and its aberrant activation is implicated in the pathogenesis of various cancers, including hepatocellular carcinoma (HCC). However, the development of clinical IRAK1 inhibitors has been hampered by a lack of sufficient selectivity over other kinases. Herein, we report the discovery of a novel IRAK1 inhibitor, A34, identified through structure-based virtual screening and structural optimization. A34 potently inhibited IRAK1 with an IC50 value of 10.6 nM and demonstrated exceptional selectivity over 215 other kinases, notably including IRAK4. Furthermore, A34 demonstrated significant anti-HCC activity both in vivo and in vitro, making it a valuable chemical probe for IRAK1 and a potential lead candidate for the treatment of HCC.","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":"117 1","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146111159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
MTEGDRP: Interpretable Molecular Self-Attention Transformer and Equivariant Graph Neural Network Based on Multi-Omics Fusion for Drug Response Prediction in Cancer Cell Lines MTEGDRP:基于多组学融合的可解释分子自关注转换器和等变图神经网络用于肿瘤细胞系药物反应预测
IF 7.3 1区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2026-02-04 DOI: 10.1021/acs.jmedchem.5c03438
Zhihan Liu,Kairui Lyu,Ya Li,Xinghui Sun,Xin Gao,Bin Yu
Cancer drug response prediction is crucial for precision medicine, as it can improve treatment outcomes and reduce medical costs. However, existing models often ignore the geometric features of drug molecules and their interactions with cancer cells. To address this, this study proposes a multiomics fusion model named MTEGDRP. The model uses a transformer to extract high-level features from drug and cell data, as well as their interactions, while an equivariant graph neural network captures the spatial structure of drugs. In regression tasks, MTEGDRP performs better than current state-of-the-art methods. Ablation studies show that multiomics integration and molecular spatial information are effective. Visualization of the feature weights provides interpretability for the model. With its excellent prediction performance, MTEGDRP shows great potential as a useful tool for guiding anticancer drug design in precision medicine.
癌症药物反应预测对精准医疗至关重要,因为它可以改善治疗效果并降低医疗成本。然而,现有的模型往往忽略了药物分子的几何特征及其与癌细胞的相互作用。为了解决这个问题,本研究提出了一个名为MTEGDRP的多组学融合模型。该模型使用变压器从药物和细胞数据中提取高级特征,以及它们之间的相互作用,而等变图神经网络捕获药物的空间结构。在回归任务中,MTEGDRP比目前最先进的方法表现得更好。消融研究表明,多组学整合和分子空间信息是有效的。特征权重的可视化为模型提供了可解释性。由于其良好的预测性能,MTEGDRP在指导精准医学抗癌药物设计方面显示出巨大的潜力。
{"title":"MTEGDRP: Interpretable Molecular Self-Attention Transformer and Equivariant Graph Neural Network Based on Multi-Omics Fusion for Drug Response Prediction in Cancer Cell Lines","authors":"Zhihan Liu,Kairui Lyu,Ya Li,Xinghui Sun,Xin Gao,Bin Yu","doi":"10.1021/acs.jmedchem.5c03438","DOIUrl":"https://doi.org/10.1021/acs.jmedchem.5c03438","url":null,"abstract":"Cancer drug response prediction is crucial for precision medicine, as it can improve treatment outcomes and reduce medical costs. However, existing models often ignore the geometric features of drug molecules and their interactions with cancer cells. To address this, this study proposes a multiomics fusion model named MTEGDRP. The model uses a transformer to extract high-level features from drug and cell data, as well as their interactions, while an equivariant graph neural network captures the spatial structure of drugs. In regression tasks, MTEGDRP performs better than current state-of-the-art methods. Ablation studies show that multiomics integration and molecular spatial information are effective. Visualization of the feature weights provides interpretability for the model. With its excellent prediction performance, MTEGDRP shows great potential as a useful tool for guiding anticancer drug design in precision medicine.","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":"57 1","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146111160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Do Amino-Oxetanes Resemble Amides? A Matched Molecular Pairs Property and Structural Comparison 氨基-氧烷与酰胺相似吗?一种匹配分子对性质及结构比较
IF 7.3 1区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2026-02-04 DOI: 10.1021/acs.jmedchem.5c02614
Hikaru Ishikura,Callum S. Begg,Juan J. Rojas,Luka Blagojevic,Gavin J. Smith,Joyce Luk,Rosemary A. Croft,Charles Romain,Chulho Choi,James A. Bull
Oxetanes display properties comparable to ketone carbonyl groups and are increasingly explored as bioisosteres. However, does the comparison hold for the most common carbonyl derivatives: do amino-oxetanes resemble amides? Here, we present a matched molecular pair study of 12 3-aryl-3-amino-oxetane and benzamide matched molecular pairs to assess their viability as isosteres. Across the surveyed physicochemical properties (pH stability, solubility, lipophilicity, clearance, permeability), amino-oxetanes exhibited broadly comparable profiles to their amide counterparts. Amino-oxetanes maintain both the H-bond acceptor and H-bond donor capabilities of analogous amides. These findings support the potential of amino-oxetanes as amide replacements. However, crystal structure analysis highlights the conformational differences and alternative exit vectors available through introduction of the oxetane ring. The preferred gauche conformation makes the torsion angle and exit vectors of amino-oxetanes more similar to sulfonamides, and therefore better like-for-like topological replacements. Overall, amino-oxetanes present an attractive design option to modulate physicochemical properties and chemical topology.
氧乙烷显示出与酮羰基相当的性质,并越来越多地作为生物同分酯被探索。然而,这种比较是否适用于最常见的羰基衍生物:氨基氧烷与酰胺相似吗?在这里,我们提出了一个匹配的分子对研究12 3-芳基-3-氨基-氧乙烷和苯酰胺匹配的分子对,以评估它们作为同位异构体的活力。在调查的物理化学性质(pH稳定性、溶解度、亲脂性、清除率、渗透性)中,氨基氧烷与酰胺类化合物表现出广泛的可比性。氨基氧烷保持了类似酰胺的氢键受体和氢键给体的能力。这些发现支持了氨基氧烷作为酰胺替代品的潜力。然而,晶体结构分析强调了构象差异和通过引入氧烷环可获得的替代出口向量。间扭构象使氨基氧烷的扭转角和出口向量与磺胺更相似,因此具有更好的同类拓扑替代。总的来说,氨基氧烷提供了一个有吸引力的设计选择来调节物理化学性质和化学拓扑结构。
{"title":"Do Amino-Oxetanes Resemble Amides? A Matched Molecular Pairs Property and Structural Comparison","authors":"Hikaru Ishikura,Callum S. Begg,Juan J. Rojas,Luka Blagojevic,Gavin J. Smith,Joyce Luk,Rosemary A. Croft,Charles Romain,Chulho Choi,James A. Bull","doi":"10.1021/acs.jmedchem.5c02614","DOIUrl":"https://doi.org/10.1021/acs.jmedchem.5c02614","url":null,"abstract":"Oxetanes display properties comparable to ketone carbonyl groups and are increasingly explored as bioisosteres. However, does the comparison hold for the most common carbonyl derivatives: do amino-oxetanes resemble amides? Here, we present a matched molecular pair study of 12 3-aryl-3-amino-oxetane and benzamide matched molecular pairs to assess their viability as isosteres. Across the surveyed physicochemical properties (pH stability, solubility, lipophilicity, clearance, permeability), amino-oxetanes exhibited broadly comparable profiles to their amide counterparts. Amino-oxetanes maintain both the H-bond acceptor and H-bond donor capabilities of analogous amides. These findings support the potential of amino-oxetanes as amide replacements. However, crystal structure analysis highlights the conformational differences and alternative exit vectors available through introduction of the oxetane ring. The preferred gauche conformation makes the torsion angle and exit vectors of amino-oxetanes more similar to sulfonamides, and therefore better like-for-like topological replacements. Overall, amino-oxetanes present an attractive design option to modulate physicochemical properties and chemical topology.","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":"22 1","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146111156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Enhancement of Potency and Selectivity of 2-Aminoquinoline-Based Human Neuronal Nitric Oxide Synthase Inhibitors 2-氨基喹啉类人神经元型一氧化氮合酶抑制剂的效价和选择性增强
IF 7.3 1区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2026-02-04 DOI: 10.1021/acs.jmedchem.5c01679
Anas Ansari,Koon Mook Kang,Huiying Li,Christine D. Hardy,Athri D. Rathnayake,Amardeep Awasthi,Thomas L. Poulos,Richard B. Silverman
Neuronal nitric oxide synthase (nNOS) is a key enzyme in neurodegenerative diseases and melanoma, making it an important therapeutic target. We previously reported 2-aminoquinoline-based nNOS inhibitors with promising activity but limited by suboptimal potency, isoform selectivity, and off-target effects. To address these issues, we designed and synthesized a new series of 7-aryl-6-fluoro-4-methyl-2-aminoquinoline derivatives. Compound 16 showed excellent potency against human nNOS (Ki 16 nM), with ∼1800-fold selectivity over human endothelial NOS (eNOS) and ∼2900-fold over human inducible NOS (iNOS). PAMPA-BBB experiments indicated high effective permeability (Pe = 13.04 × 10–6 cm/s), suggesting strong CNS drug potential. In vivo pharmacokinetic studies in mice further demonstrated sustained systemic exposure, low clearance, and robust brain penetration. In contrast, compound 24, the N-Me analogue of 16, was inactive. Molecular dynamics simulations indicated that N-methylation disrupted the favorable solvation of the tail amino group, likely contributing to its loss of activity and nNOS affinity.
神经元一氧化氮合酶(nNOS)是神经退行性疾病和黑色素瘤的关键酶,是重要的治疗靶点。我们之前报道了基于2-氨基喹啉的nNOS抑制剂具有良好的活性,但受到次优效价、异构体选择性和脱靶效应的限制。为了解决这些问题,我们设计并合成了一系列新的7-芳基-6-氟-4-甲基-2-氨基喹啉衍生物。化合物16对人nNOS (Ki 16 nM)表现出极好的抑制作用,对人内皮NOS (eNOS)和人诱导NOS (iNOS)的选择性分别为~ 1800倍和~ 2900倍。PAMPA-BBB实验显示其具有较高的有效通透性(Pe = 13.04 × 10-6 cm/s),具有较强的中枢神经系统药物潜力。小鼠体内药代动力学研究进一步证明了持续的全身暴露、低清除率和强大的脑穿透性。而16的N-Me类似物化合物24则无活性。分子动力学模拟表明,n -甲基化破坏了尾部氨基的有利溶剂化,可能导致其活性和nNOS亲和力的丧失。
{"title":"Enhancement of Potency and Selectivity of 2-Aminoquinoline-Based Human Neuronal Nitric Oxide Synthase Inhibitors","authors":"Anas Ansari,Koon Mook Kang,Huiying Li,Christine D. Hardy,Athri D. Rathnayake,Amardeep Awasthi,Thomas L. Poulos,Richard B. Silverman","doi":"10.1021/acs.jmedchem.5c01679","DOIUrl":"https://doi.org/10.1021/acs.jmedchem.5c01679","url":null,"abstract":"Neuronal nitric oxide synthase (nNOS) is a key enzyme in neurodegenerative diseases and melanoma, making it an important therapeutic target. We previously reported 2-aminoquinoline-based nNOS inhibitors with promising activity but limited by suboptimal potency, isoform selectivity, and off-target effects. To address these issues, we designed and synthesized a new series of 7-aryl-6-fluoro-4-methyl-2-aminoquinoline derivatives. Compound 16 showed excellent potency against human nNOS (Ki 16 nM), with ∼1800-fold selectivity over human endothelial NOS (eNOS) and ∼2900-fold over human inducible NOS (iNOS). PAMPA-BBB experiments indicated high effective permeability (Pe = 13.04 × 10–6 cm/s), suggesting strong CNS drug potential. In vivo pharmacokinetic studies in mice further demonstrated sustained systemic exposure, low clearance, and robust brain penetration. In contrast, compound 24, the N-Me analogue of 16, was inactive. Molecular dynamics simulations indicated that N-methylation disrupted the favorable solvation of the tail amino group, likely contributing to its loss of activity and nNOS affinity.","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":"20 1","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146111155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Design and Synthesis of Membrane-Targeting Poly-Ruthenium Complexes Containing Quaternary Ammonium Cations with Potential Antibacterial Activity against Methicillin-Resistant Staphylococcus aureus (MRSA) 对耐甲氧西林金黄色葡萄球菌(MRSA)具有潜在抗菌活性的季铵阳离子膜靶向多钌配合物的设计与合成
IF 7.3 1区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2026-02-04 DOI: 10.1021/acs.jmedchem.5c02644
Runyu Xue,Cunhong Luo,Lixin Dou,Xinru Yu,Liao Xiangwen,Wang Jintao,Rujian Yu,Yanshi Xiong
The escalating threat of Methicillin-resistant Staphylococcus aureus (MRSA) infections seriously endangers human health, so facing the immense threat of drug-resistant bacteria, discovering new and potent antibacterial drugs less prone to inducing resistance is urgently needed. In this study, four amphiphilic ruthenium polypyridyl complexes were synthesized, namely [Ru(II)(bpy)2(DIPPB)] (PF6)3 (Ru-1), [Ru(II)(dmb)2(DIPPB)] (PF6)3 (Ru-2), [Ru(II)(dmob)2(DIPPB)] (PF6)3 (Ru-3) and [Ru(II)(bpy)2(DIPPB)] (PF6)3 (Ru-4). Among these complexes, complex Ru-4 incorporates N-methylimidazole and quaternary ammonium cations, in vitro experiments have demonstrated the presence of potent antibacterial activity against Staphylococcus aureus and MRSA, accompanied by low hemolytic activity and a diminished tendency to induce drug resistance. It acts by disrupting bacterial membranes via interaction with phosphatidylglycerol and phosphatidylethanolamine, increasing permeability, elevating ROS levels, and causing content leakage. Transcriptomics confirmed its impact on membrane-related genes. Notably, in vivo experimental results demonstrated that Ru-4 exhibits superior efficacy compared to vancomycin, thereby identifying it as a promising therapeutic candidate for MRSA infection treatment.
耐甲氧西林金黄色葡萄球菌(MRSA)感染威胁日益严重,严重危害人类健康,面对耐药菌的巨大威胁,迫切需要发现不易产生耐药的新型强效抗菌药物。本研究合成了四种两亲性钌多吡啶基配合物,分别为[Ru(II)(bpy)2(DIPPB)] (PF6)3 (Ru-1)、[Ru(II)(dmb)2(DIPPB)] (PF6)3 (Ru-2)、[Ru(II)(dmob)2(DIPPB)] (PF6)3 (Ru-3)和[Ru(II)(bpy)2(DIPPB)] (PF6)3 (Ru-4)。在这些配合物中,配合物Ru-4含有n -甲基咪唑和季铵阳离子,体外实验证明其对金黄色葡萄球菌和MRSA具有较强的抗菌活性,同时具有较低的溶血活性,诱导耐药的倾向减弱。它的作用是通过与磷脂酰甘油和磷脂酰乙醇胺相互作用破坏细菌膜,增加渗透性,提高ROS水平,并导致内容物泄漏。转录组学证实了其对膜相关基因的影响。值得注意的是,体内实验结果表明,与万古霉素相比,Ru-4具有优越的疗效,从而确定其是治疗MRSA感染的有希望的候选药物。
{"title":"Design and Synthesis of Membrane-Targeting Poly-Ruthenium Complexes Containing Quaternary Ammonium Cations with Potential Antibacterial Activity against Methicillin-Resistant Staphylococcus aureus (MRSA)","authors":"Runyu Xue,Cunhong Luo,Lixin Dou,Xinru Yu,Liao Xiangwen,Wang Jintao,Rujian Yu,Yanshi Xiong","doi":"10.1021/acs.jmedchem.5c02644","DOIUrl":"https://doi.org/10.1021/acs.jmedchem.5c02644","url":null,"abstract":"The escalating threat of Methicillin-resistant Staphylococcus aureus (MRSA) infections seriously endangers human health, so facing the immense threat of drug-resistant bacteria, discovering new and potent antibacterial drugs less prone to inducing resistance is urgently needed. In this study, four amphiphilic ruthenium polypyridyl complexes were synthesized, namely [Ru(II)(bpy)2(DIPPB)] (PF6)3 (Ru-1), [Ru(II)(dmb)2(DIPPB)] (PF6)3 (Ru-2), [Ru(II)(dmob)2(DIPPB)] (PF6)3 (Ru-3) and [Ru(II)(bpy)2(DIPPB)] (PF6)3 (Ru-4). Among these complexes, complex Ru-4 incorporates N-methylimidazole and quaternary ammonium cations, in vitro experiments have demonstrated the presence of potent antibacterial activity against Staphylococcus aureus and MRSA, accompanied by low hemolytic activity and a diminished tendency to induce drug resistance. It acts by disrupting bacterial membranes via interaction with phosphatidylglycerol and phosphatidylethanolamine, increasing permeability, elevating ROS levels, and causing content leakage. Transcriptomics confirmed its impact on membrane-related genes. Notably, in vivo experimental results demonstrated that Ru-4 exhibits superior efficacy compared to vancomycin, thereby identifying it as a promising therapeutic candidate for MRSA infection treatment.","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":"159 1","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146111157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 and Preclinical Evaluation of TPM003: A Novel GLP-1/GIP/Glucagon Triple Hormone Receptor Agonist with Robust Efficacy in Obesity and NASH TPM003的发现和临床前评估:一种新型GLP-1/GIP/胰高血糖素三重激素受体激动剂,对肥胖和NASH具有强大的疗效
IF 7.3 1区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2026-02-04 DOI: 10.1021/acs.jmedchem.5c03845
Nan Zheng, Longfang Tu, Pu Xu, Rongfang Chen, Jiang Lu, Wan Dai, Yanxia Lin, Jianmei Ouyang, Jinying Qiu, You Wang, Leiming Wang, Weijun Shen
Harnessing the simultaneous activation of GLP-1R, GIPR, and GCGR has emerged as a highly promising therapeutic paradigm for obesity and related metabolic diseases, including nonalcoholic steatohepatitis (NASH). Here, we report the discovery of TPM003, a novel unimolecular GLP-1R/GIPR/GCGR triple agonist engineered by using a long-acting PEG-fatty acid (PEG-FA) stapling technology. TPM003 exhibits balanced triple receptor agonism and demonstrates an extended systemic half-life across multiple species. In obese mice, TPM003 induced robust and durable weight loss, accompanied by broad improvements in metabolic parameters, outperforming current GLP-1RA standards. Importantly, TPM003 also effectively reversed hepatic steatosis and improved markers of liver function in multiple NASH models. Furthermore, TPM003 is compatible with SNAC-based absorption enhancement, enabling oral delivery in a tablet formulation. Collectively, these findings highlight the therapeutic advantages of balanced GLP-1R/GIPR/GCGR agonism for obesity and NASH and support TPM003 as a promising preclinical candidate with translational potential.
利用GLP-1R、GIPR和GCGR的同时激活已经成为一种非常有前途的治疗肥胖和相关代谢疾病的范例,包括非酒精性脂肪性肝炎(NASH)。在这里,我们报告了TPM003的发现,这是一种新型的单分子GLP-1R/GIPR/GCGR三重激动剂,采用长效peg -脂肪酸(PEG-FA)钉接技术进行工程设计。TPM003表现出平衡的三重受体激动作用,并在多个物种中表现出延长的系统半衰期。在肥胖小鼠中,TPM003诱导了稳健和持久的体重减轻,并伴随着代谢参数的广泛改善,优于当前的GLP-1RA标准。重要的是,TPM003在多种NASH模型中也能有效逆转肝脂肪变性和改善肝功能标志物。此外,TPM003与基于snac的吸收增强相容,能够以片剂形式口服给药。总的来说,这些发现强调了GLP-1R/GIPR/GCGR平衡激动作用对肥胖和NASH的治疗优势,并支持TPM003作为具有转化潜力的临床前候选药物。
{"title":"Discovery and Preclinical Evaluation of TPM003: A Novel GLP-1/GIP/Glucagon Triple Hormone Receptor Agonist with Robust Efficacy in Obesity and NASH","authors":"Nan Zheng, Longfang Tu, Pu Xu, Rongfang Chen, Jiang Lu, Wan Dai, Yanxia Lin, Jianmei Ouyang, Jinying Qiu, You Wang, Leiming Wang, Weijun Shen","doi":"10.1021/acs.jmedchem.5c03845","DOIUrl":"https://doi.org/10.1021/acs.jmedchem.5c03845","url":null,"abstract":"Harnessing the simultaneous activation of GLP-1R, GIPR, and GCGR has emerged as a highly promising therapeutic paradigm for obesity and related metabolic diseases, including nonalcoholic steatohepatitis (NASH). Here, we report the discovery of TPM003, a novel unimolecular GLP-1R/GIPR/GCGR triple agonist engineered by using a long-acting PEG-fatty acid (PEG-FA) stapling technology. TPM003 exhibits balanced triple receptor agonism and demonstrates an extended systemic half-life across multiple species. In obese mice, TPM003 induced robust and durable weight loss, accompanied by broad improvements in metabolic parameters, outperforming current GLP-1RA standards. Importantly, TPM003 also effectively reversed hepatic steatosis and improved markers of liver function in multiple NASH models. Furthermore, TPM003 is compatible with SNAC-based absorption enhancement, enabling oral delivery in a tablet formulation. Collectively, these findings highlight the therapeutic advantages of balanced GLP-1R/GIPR/GCGR agonism for obesity and NASH and support TPM003 as a promising preclinical candidate with translational potential.","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":"31 1","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146116010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Structure–Activity Relationship and Crystallographic Study of New Monobactams 新型单菌酰胺的构效关系及晶体学研究
IF 7.3 1区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2026-02-03 DOI: 10.1021/acs.jmedchem.5c02427
Vid Kavaš, Carlos Contreras-Martel, Stane Pajk, Damijan Knez, Alexandre Martins, Thomas A. Gould, David I. Roper, Irena Zdovc, Andréa Dessen, Martina Hrast Rambaher, Stanislav Gobec
Monobactams, a subclass of β-lactam antibiotics with a monocyclic scaffold, are uniquely resistant to hydrolysis by metallo-β-lactamases, providing a distinct therapeutic advantage. Here, we report an in silico-based structure–activity relationship (SAR) investigation of aztreonam-related monobactams. A focused library of monobactam derivatives was synthesized and evaluated for inhibition of penicillin-binding proteins (PBPs) and antibacterial activity. Ten compounds, including aztreonam, were crystallized with truncated PBP1b from Streptococcus pneumoniae, used as a model PBP. Potent PBP1b inhibitors were developed, although high enzymatic potency was not always reflected in strong antibacterial activity. Certain derivatives showed activity against Staphylococcus aureus, which is typically resistant to monobactams. 2D similarity search identified potent inhibitors active against Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii. Crystal structures revealed previously unrecognized binding interactions, including a halogen bond with a conserved threonine residue, underscoring the potential of these interactions to support the development of more potent PBP inhibitors.
Monobactams是具有单环支架的β-内酰胺类抗生素的一个亚类,具有独特的抗金属β-内酰胺酶水解能力,具有独特的治疗优势。在这里,我们报道了一种基于硅基的氮唑南相关单菌菌的构效关系(SAR)研究。合成了单巴坦衍生物的重点文库,并对其抑制青霉素结合蛋白(PBPs)和抗菌活性进行了评价。包括氮曲南在内的10种化合物与肺炎链球菌截短的PBP1b结晶,作为PBP模型。有效的PBP1b抑制剂被开发出来,尽管高酶效并不总是反映在强抗菌活性上。某些衍生物显示出抗金黄色葡萄球菌的活性,而金黄色葡萄球菌通常对单结核菌具有抗性。二维相似性搜索发现了对大肠杆菌、肺炎克雷伯菌和鲍曼不动杆菌有活性的有效抑制剂。晶体结构揭示了以前未被识别的结合相互作用,包括与保守苏氨酸残基的卤素键,强调了这些相互作用的潜力,以支持开发更有效的PBP抑制剂。
{"title":"Structure–Activity Relationship and Crystallographic Study of New Monobactams","authors":"Vid Kavaš, Carlos Contreras-Martel, Stane Pajk, Damijan Knez, Alexandre Martins, Thomas A. Gould, David I. Roper, Irena Zdovc, Andréa Dessen, Martina Hrast Rambaher, Stanislav Gobec","doi":"10.1021/acs.jmedchem.5c02427","DOIUrl":"https://doi.org/10.1021/acs.jmedchem.5c02427","url":null,"abstract":"Monobactams, a subclass of β-lactam antibiotics with a monocyclic scaffold, are uniquely resistant to hydrolysis by metallo-β-lactamases, providing a distinct therapeutic advantage. Here, we report an <i>in silico</i>-based structure–activity relationship (SAR) investigation of aztreonam-related monobactams. A focused library of monobactam derivatives was synthesized and evaluated for inhibition of penicillin-binding proteins (PBPs) and antibacterial activity. Ten compounds, including aztreonam, were crystallized with truncated PBP1b from <i>Streptococcus pneumoniae</i>, used as a model PBP. Potent PBP1b inhibitors were developed, although high enzymatic potency was not always reflected in strong antibacterial activity. Certain derivatives showed activity against <i>Staphylococcus aureus</i>, which is typically resistant to monobactams. 2D similarity search identified potent inhibitors active against <i>Escherichia coli</i>, <i>Klebsiella pneumoniae</i>, and <i>Acinetobacter baumannii</i>. Crystal structures revealed previously unrecognized binding interactions, including a halogen bond with a conserved threonine residue, underscoring the potential of these interactions to support the development of more potent PBP inhibitors.","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":"23 1","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146102043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
期刊
Journal of Medicinal Chemistry
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1