ChemMedChem最新文献_第7页

Molecular Engineering of Cordycepin Derivatives for Enhanced Biological Activity and Stability. 虫草素衍生物增强生物活性和稳定性的分子工程研究。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-02-05 DOI: 10.1002/cmdc.202400979

Yiming Gu, Wei Yu, Xiang Li, Yingjie Fan, Yanan Liu, Jumreang Tummatorn, Siyu Jiang, Jingyue Yang

引用次数: 0

Synthesis and Antibacterial Properties of 3-Amino-β-Lactams Bearing a Heteroatom-Containing C4 Substituent. 含杂原子C4取代基3-氨基β-内酰胺的合成及抗菌性能。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-02-05 DOI: 10.1002/cmdc.202400994

Kato Bredael, Fien Vanhecke, Emma Vandenheede, Christian V Stevens, Stanislav Gobec, Matthias D'hooghe

{"title":"Synthesis and Antibacterial Properties of 3-Amino-β-Lactams Bearing a Heteroatom-Containing C4 Substituent.","authors":"Kato Bredael, Fien Vanhecke, Emma Vandenheede, Christian V Stevens, Stanislav Gobec, Matthias D'hooghe","doi":"10.1002/cmdc.202400994","DOIUrl":"10.1002/cmdc.202400994","url":null,"abstract":"The rise of antimicrobial resistance has spurred the search for innovative antibiotics, with monocyclic 3-amino-β-lactams - aztreonam standing out as key example - showing significant potential. In particular, C4-functionalized 3-amino-β-lactams have emerged as a promising subclass that can potentially improve the activity, stability and cellular permeability of the compounds. This review outlines various synthetic methodologies available for the construction of 3-amino-β-lactams bearing a heteroatom-containing substituent at C4, with the heteroatom connected to the ring system either directly or via a methylene bridge. Special attention is devoted to 3-amino-4-hydroxymethyl-β-lactams and 3-amino-4-acetoxy-β-lactams as versatile synthetic intermediates. Moreover, the effect of these C4 substituents on the biological activity of the corresponding 3-amino-β-lactams is discussed in detail. A better understanding of synthetic protocols and antibacterial properties related to this underexplored class of monocyclic 3-amino-β-lactams might contribute to address the current antibiotics problems we are facing more efficiently.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202400994"},"PeriodicalIF":3.6,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187827","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

Front Cover: 3’-Dehydroxypurpurogallin-4-Carboxamides as Influenza A Endonuclease Inhibitors: Synthesis, Structure-Activity Relationship Analysis, and Structural Characterization of Protein Complex (ChemMedChem 3/2025) 前封面：3 ' -Dehydroxypurpurogallin-4-Carboxamides作为甲型流感内切酶抑制剂：合成、结构-活性关系分析和蛋白质复合物的结构表征（ChemMedChem 3/2025）

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-02-04 DOI: 10.1002/cmdc.202580301

Michal Kráľ, Tomáš Kotačka, Róbert Reiberger, Gabriela Panýrková, Kateřina Radilová, Zuzana Osifová, Miroslav Flieger, Jan Konvalinka, Pavel Majer, Milan Kožíšek, Aleš Machara

{"title":"Front Cover: 3’-Dehydroxypurpurogallin-4-Carboxamides as Influenza A Endonuclease Inhibitors: Synthesis, Structure-Activity Relationship Analysis, and Structural Characterization of Protein Complex (ChemMedChem 3/2025)","authors":"Michal Kráľ, Tomáš Kotačka, Róbert Reiberger, Gabriela Panýrková, Kateřina Radilová, Zuzana Osifová, Miroslav Flieger, Jan Konvalinka, Pavel Majer, Milan Kožíšek, Aleš Machara","doi":"10.1002/cmdc.202580301","DOIUrl":"https://doi.org/10.1002/cmdc.202580301","url":null,"abstract":"The image shows a scene where the mushroom motif is linked to the chemical formulas of purpurogallin derivatives – colchicine, fomenanthriol, and aurantricholone – natural pigments in mushroom caps. These compounds appear as orange, red, or brown dyes, echoing the mushrooms’ colors. It also represents the mushroom season, popular in Europe during autumn. A blue “shield” symbolizes the protective effect of our developed purpurogallines, which block influenza endonuclease, depicted as scissors ready to cleave RNA. More details can be found in article 10.1002/cmdc.202400577 by Milan Kožíšek, Aleš Machara, and co-workers.<figure>\u0000 <div><picture>\u0000 <source></source></picture>\u0000 </div>\u0000 </figure>\u0000 ","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"20 3","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cmdc.202580301","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143111882","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

Cover Feature: Diversity Oriented Strategy (DOS) for the Efficient Synthesis of Benzofuro[2,3-b]pyridine Derivatives with Anticancer Activity (ChemMedChem 3/2025) 封面专题：多样性导向策略（DOS）高效合成具有抗癌活性的苯并呋喃[2,3-b]吡啶衍生物（ChemMedChem 3/2025）

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-02-04 DOI: 10.1002/cmdc.202580302

Reymark Ereje, Jantana Yahuafai, Theeranuch Jaroenchuensiri, Patcharaporn Supakijjanusorn, Sukanya Unson, Borwornlak Toopradab, Thanyada Rungrotmongkol, Somsak Pianwanit, Chanat Aonbangkhen, Tanatorn Khotavivattana

引用次数: 0

Structure-Atropisomer Stability Relationship in Selective MCL-1 Inhibitors. 选择性MCL-1抑制剂的结构-缩二聚体稳定性关系。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-02-03 DOI: 10.1002/cmdc.202400970

Szabolcs Sipos, Barbara Balazs, Tamas Gati, Márton Csékei, Mihály Kováacs, Zoltan Szlavik, Attila Paczal, Balázs Bálint, James B Murray, James Davidson, Roderick E Hubbard, Gaëtane Le Toumelin-Braizat, Ana Leticia Maragno, Olivier Geneste, András Stirling, András Kotschy

{"title":"Structure-Atropisomer Stability Relationship in Selective MCL-1 Inhibitors.","authors":"Szabolcs Sipos, Barbara Balazs, Tamas Gati, Márton Csékei, Mihály Kováacs, Zoltan Szlavik, Attila Paczal, Balázs Bálint, James B Murray, James Davidson, Roderick E Hubbard, Gaëtane Le Toumelin-Braizat, Ana Leticia Maragno, Olivier Geneste, András Stirling, András Kotschy","doi":"10.1002/cmdc.202400970","DOIUrl":"10.1002/cmdc.202400970","url":null,"abstract":"Atropisomersm is an emerging feature in recent drug candidates due to the increasing complexity of the targeted protein surfaces. The developability of the drug candidates requires that their atropisomer interconversion is either fast or very slow at ambient temperature therefore the understanding and predictability of the isomerization rate is of great importance. Through a series of selective MCL-1 inhibitors we studied how structural features influence the interconversion of atropisomers. Besides basic observations such as stability in solution, we also carried out NMR kinetics at varying temperatures and a quantum chemical assessment of the isomerization process. The results of our theoretical studies and experimental investigations matched nicely when it came to predicting the presence or absence of isomerization at ambient temperature. For certain compounds we also measured the rotational barrier that fitted nicely the predicted values. The better understanding of how structural elements impact atropisomer stability enables the more efficient optimization of this important feature.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202400970"},"PeriodicalIF":3.6,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078076","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

Oxidative Coupling of Guanidines and Isocyanides Catalyzed by Nickel(II): Access to Imidazoline Derivatives with Antibacterial Activity 镍催化下胍和异氰酸酯的氧化偶联：一种具有抗菌活性的咪唑啉衍生物的制备方法。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-02-02 DOI: 10.1002/cmdc.202400904

Georgii A. Gavrilov, Tuan K. Nguyen, Dr. Svetlana A. Katkova, Dr. Nikolai V. Rostovskii, Dr. Elizaveta V. Rogacheva, Dr. Liudmila A. Kraeva, Dr. Mikhail A. Kinzhalov

引用次数: 0

Lamellarin D Acts as an Inhibitor of Type I Collagen Production. 薄层蛋白D作为I型胶原蛋白生成的抑制剂。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-01-30 DOI: 10.1002/cmdc.202401001

Daisuke Okuno, Noriho Sakamoto, Hideki Hayashi, Tsutomu Fukuda, Yoshiko Akiyama, Chiaki Iketani, Ritsuko Murakami, Takatomo Tokito, Takuto Miyamura, Hirokazu Yura, Takashi Kido, Hiroshi Ishimoto, Shinnosuke Takemoto, Takahiro Takazono, Tomoya Nishino, Yuji Ishimatsu, Jun Ishihara, Kohsuke Takeda, Yoshimasa Tanaka, Hiroshi Mukae

{"title":"Lamellarin D Acts as an Inhibitor of Type I Collagen Production.","authors":"Daisuke Okuno, Noriho Sakamoto, Hideki Hayashi, Tsutomu Fukuda, Yoshiko Akiyama, Chiaki Iketani, Ritsuko Murakami, Takatomo Tokito, Takuto Miyamura, Hirokazu Yura, Takashi Kido, Hiroshi Ishimoto, Shinnosuke Takemoto, Takahiro Takazono, Tomoya Nishino, Yuji Ishimatsu, Jun Ishihara, Kohsuke Takeda, Yoshimasa Tanaka, Hiroshi Mukae","doi":"10.1002/cmdc.202401001","DOIUrl":"10.1002/cmdc.202401001","url":null,"abstract":"Idiopathic pulmonary fibrosis (IPF) is a progressive and chronic interstitial lung disease characterized by irreversible loss of lung function and a poor prognosis. Type I collagen, a major component of the extracellular matrix, plays a central role in the pathogenesis of fibrosis and is considered a key molecular target for therapeutic intervention. While current anti-fibrotic therapies demonstrate limited efficacy in slowing disease progression, their clinical impact remains suboptimal due to poor pharmacokinetic properties and non-curative therapy. Moreover, the development of effective anti-fibrotic agents targeting collagen synthesis is hindered by the absence of robust, cost-effective, high-throughput drug screening platforms. In this study, we established a novel screening system designed to identify small molecules that inhibit the expression of the COL1A2 gene, which encodes type I collagen. Utilizing this system, we screened a library of natural and synthetic compounds developed at Nagasaki University and identified lamellarin D as a potent inhibitor of COL1A2 expression and subsequent type I collagen production. These findings suggest that lamellarin D, through its unique molecular mechanism, may serve as the foundation for the development of a new class of IPF treatments aimed at targeting the underlying fibrotic processes.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202401001"},"PeriodicalIF":3.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062834","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

Design and Synthesis of Tetrahydropyrrolo[3,4-c]Pyrazole Sigma-1 Receptor Ligands. 四氢吡咯[3,4-c]吡唑Sigma-1受体配体的设计与合成。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-01-30 DOI: 10.1002/cmdc.202401015

Giuseppe Cosentino, Maria Dichiara, Giuliana Costanzo, Alessandro Coco, Lorella Pasquinucci, Agostino Marrazzo, Antonio Rescifina, Emanuele Amata

{"title":"Design and Synthesis of Tetrahydropyrrolo[3,4-c]Pyrazole Sigma-1 Receptor Ligands.","authors":"Giuseppe Cosentino, Maria Dichiara, Giuliana Costanzo, Alessandro Coco, Lorella Pasquinucci, Agostino Marrazzo, Antonio Rescifina, Emanuele Amata","doi":"10.1002/cmdc.202401015","DOIUrl":"10.1002/cmdc.202401015","url":null,"abstract":"This study presents a series of tetrahydropyrrolo[3,4-c]pyrazole-based compounds designed as sigma-1 receptor (S1R) ligands, focusing on optimizing affinity and reducing off-target effects. We synthesized various derivatives from commercially available precursors and, through radioligand binding assays, assessed their binding affinity for S1R and sigma-2 receptor (S2R). Compound 19 (AD417), containing a benzyl group and an amide substituent, demonstrated notable S1R affinity (Ki=75 nM) with 6-fold selectivity over S2R. Modifications on the pyrrolidine nitrogen were crucial in enhancing receptor interaction, as the protonated nitrogen likely interacts with Glu172 within the S1R binding site. Furthermore, to address hERG potassium ion channel inhibition, a known limitation in S1R drug development, we evaluated compound 19's cardiotoxicity potential. With an experimental hERG IC50 of 5.8 μM, significantly higher than verapamil's IC50 of 0.41 μM, and haloperidol's IC50 of 0.16 μM, compound 19 showed a safer profile, suggesting a reduced risk of cardiotoxicity. These findings underscore the role of nitrogen accessibility, structural flexibility, and functional group modifications in optimizing S1R ligand interactions and provide a promising foundation for developing safer S1R-targeted therapeutics with minimized hERG-related risks.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202401015"},"PeriodicalIF":3.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062831","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

ABT, Elacridar and Bile-Duct Cannulated Rats: Tools to Understand Pharmacokinetics ABT，埃拉西达和胆管插管大鼠：了解药代动力学的工具。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-01-28 DOI: 10.1002/cmdc.202400995

Gilles Ouvry

引用次数: 0

Machine Learning-Driven Discovery of Structurally Related Natural Products as Activators of the Cardiac Calcium Pump SERCA2a. 机器学习驱动下发现结构相关的天然产物作为心脏钙泵SERCA2a的激活剂。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-01-23 DOI: 10.1002/cmdc.202400913

Carlos Cruz-Cortés, Eli Fernández-de Gortari, Rodrigo Aguayo-Ortiz, Jaroslava Šeflová, Adam Ard, Martin Clasby, Justus Anumonwo, L Michel Espinoza-Fonseca

{"title":"Machine Learning-Driven Discovery of Structurally Related Natural Products as Activators of the Cardiac Calcium Pump SERCA2a.","authors":"Carlos Cruz-Cortés, Eli Fernández-de Gortari, Rodrigo Aguayo-Ortiz, Jaroslava Šeflová, Adam Ard, Martin Clasby, Justus Anumonwo, L Michel Espinoza-Fonseca","doi":"10.1002/cmdc.202400913","DOIUrl":"10.1002/cmdc.202400913","url":null,"abstract":"A key molecular dysfunction in heart failure is the reduced activity of the cardiac sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) in cardiac muscle cells. Reactivating SERCA2a improves cardiac function in heart failure models, making it a validated target and an attractive therapeutic approach for heart failure therapy. However, finding small-molecule SERCA2a activators is challenging. In this study, we used a machine learning-based virtual screening to identify SERCA2a activators among 57,423 natural products. The machine learning model identified ten structurally related natural products from Zingiber officinale, Aframomum melegueta, Alpinia officinarum, Alpinia oxyphylla, and Capsicum (chili peppers) as SERCA2a activators. Initial ATPase assays showed seven of these activate SERCA at low micromolar concentrations. Notably, two natural products, Yakuchinone A and Alpinoid D displayed robust concentration-dependent responses in primary ATPase activity assays, efficient lipid bilayer binding and permeation in atomistic simulations, and enhanced intracellular Ca2+ transport in adult mouse cardiac cells. While these natural products exert off-target effects on Ca2+ signaling, these compounds offer promising avenues for the design and optimization of lead compounds. In conclusion, this study increases the array of calcium pump effectors and provides new scaffolds for the development of novel SERCA2a activators as new therapies for heart failure.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202400913"},"PeriodicalIF":3.6,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031558","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