{"title":"Announcing the 2024 ACS Division of Medicinal Chemistry Award Recipients: Celebrating Excellence in Medicinal Chemistry","authors":"Lori Ferrins, and , Paul C. Trippier, ","doi":"10.1021/acsmedchemlett.5c0025710.1021/acsmedchemlett.5c00257","DOIUrl":"https://doi.org/10.1021/acsmedchemlett.5c00257https://doi.org/10.1021/acsmedchemlett.5c00257","url":null,"abstract":"","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"16 6","pages":"902–905 902–905"},"PeriodicalIF":3.5,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144261073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Announcing the 2024 ACS Division of Medicinal Chemistry Award Recipients: Celebrating Excellence in Medicinal Chemistry.","authors":"Lori Ferrins, Paul C Trippier","doi":"10.1021/acsmedchemlett.5c00257","DOIUrl":"https://doi.org/10.1021/acsmedchemlett.5c00257","url":null,"abstract":"","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"16 6","pages":"902-905"},"PeriodicalIF":3.5,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12169596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Novel Substituted Pyrazoles as 5-HT1A Agonists for Treating Neuropsychiatric Diseases","authors":"Ram W. Sabnis*, ","doi":"10.1021/acsmedchemlett.5c0030610.1021/acsmedchemlett.5c00306","DOIUrl":"https://doi.org/10.1021/acsmedchemlett.5c00306https://doi.org/10.1021/acsmedchemlett.5c00306","url":null,"abstract":"<p >Provided herein are novel substituted pyrazoles as 5-HT1A agonists, pharmaceutical compositions, use of such compounds in treating neuropsychiatric diseases, and processes for preparing such compounds.</p>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"16 6","pages":"978–979 978–979"},"PeriodicalIF":3.5,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144261099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Novel Substituted Pyrazoles as 5‑HT1A Agonists for Treating Neuropsychiatric Diseases.","authors":"Ram W Sabnis","doi":"10.1021/acsmedchemlett.5c00306","DOIUrl":"10.1021/acsmedchemlett.5c00306","url":null,"abstract":"<p><p>Provided herein are novel substituted pyrazoles as 5-HT1A agonists, pharmaceutical compositions, use of such compounds in treating neuropsychiatric diseases, and processes for preparing such compounds.</p>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"16 6","pages":"978-979"},"PeriodicalIF":3.5,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12169453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aleksei A. Logvinov, Geert Rombouts, Matthieu Jouffroy* and Steven P. Nolan*,
{"title":"Suzuki–Miyaura Coupling of Pinacolboronic Esters Catalyzed by a Well-Defined Palladium N-Heterocyclic Carbene (NHC) Catalyst","authors":"Aleksei A. Logvinov, Geert Rombouts, Matthieu Jouffroy* and Steven P. Nolan*, ","doi":"10.1021/acsmedchemlett.5c0020610.1021/acsmedchemlett.5c00206","DOIUrl":"https://doi.org/10.1021/acsmedchemlett.5c00206https://doi.org/10.1021/acsmedchemlett.5c00206","url":null,"abstract":"<p >We report a versatile synthetic method for coupling heteroaryl chlorides and bromides with (hetero)aryl pinacolboronic esters of pharmaceutical interest at low catalyst loading of a well-defined palladium-NHC catalyst providing products in good to high isolated yield and purity in short reaction time. The method displays remarkably broad applicability with both 5- and 6-membered heterocycles.</p>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"16 6","pages":"1170–1174 1170–1174"},"PeriodicalIF":3.5,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144261086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marta Clariano, Diogo Nunes, Daniela Canudo, Daniela Maçãs, Bruno J. L. Castro, Audrey Jordaan, Pedro Gomes, Anna Contini, João Perdigão, Isabel Portugal, Margarida Madureira, Digby F. Warner, Marco Pieroni, Maria de Jesus Perry* and Francisca Lopes*,
{"title":"Pyrroloquinolone-Based Compounds as a Novel Antimycobacterial Chemotype","authors":"Marta Clariano, Diogo Nunes, Daniela Canudo, Daniela Maçãs, Bruno J. L. Castro, Audrey Jordaan, Pedro Gomes, Anna Contini, João Perdigão, Isabel Portugal, Margarida Madureira, Digby F. Warner, Marco Pieroni, Maria de Jesus Perry* and Francisca Lopes*, ","doi":"10.1021/acsmedchemlett.5c0018310.1021/acsmedchemlett.5c00183","DOIUrl":"https://doi.org/10.1021/acsmedchemlett.5c00183https://doi.org/10.1021/acsmedchemlett.5c00183","url":null,"abstract":"<p >Tuberculosis, caused by <i>Mycobacterium tuberculosis</i> (Mtb), remains the world’s most lethal infectious disease, posing an uncontained health challenge. The major hurdles are the long treatments and low patient compliance that leads to the appearance of resistance, as well as the lack of drugs that effectively tackle the latent infections. Herein we report the development of compounds with the ability to target the electron transport chain of Mtb by inhibiting cytochrome <i>bcc</i> (cyt-<i>bcc</i>) (<b>7a</b>–<b>i</b>) and additionally being capable of inhibiting cytochrome <i>bd</i> (cyt-<i>bd</i>) (<b>7j</b> and <b>7k</b>). We present the synthesis, determination of physicochemical properties, evaluation of the antibacterial activity, and cytotoxicity assessment of pyrroloquinolone-based compounds. The antibacterial evaluation of <b>7a</b>–<b>k</b> showed selectivity toward mycobacteria, and the results identify cyt-<i>bcc</i> as their target. Compounds <b>7j</b> and <b>7k</b> presented promising results against Mtb and good physicochemical properties. Cytotoxicity assays revealed a good safety profile regarding the toxicity for human cell lines.</p>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"16 6","pages":"1139–1146 1139–1146"},"PeriodicalIF":3.5,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144261042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Javier L. Baylon*, Matthew J. Chalkley, Tony Siu, Wilson Shou, Yongnian Sun, Xianmei Cai, Anthony Paiva, Shivani Patel, Tatyana Zvyaga and Dahlia R. Weiss,
{"title":"New Multiparameter Index Is a Strong Predictor of Oral Bioavailability for Heterobifunctional Degraders","authors":"Javier L. Baylon*, Matthew J. Chalkley, Tony Siu, Wilson Shou, Yongnian Sun, Xianmei Cai, Anthony Paiva, Shivani Patel, Tatyana Zvyaga and Dahlia R. Weiss, ","doi":"10.1021/acsmedchemlett.5c0015610.1021/acsmedchemlett.5c00156","DOIUrl":"https://doi.org/10.1021/acsmedchemlett.5c00156https://doi.org/10.1021/acsmedchemlett.5c00156","url":null,"abstract":"<p >Ligand-directed degraders (LDDs) are heterobifunctional molecules that degrade proteins by engaging the ubiquitin-protein-ligase (E3) system. LDDs (also known as proteolysis-targeting chimeras) consist of a target-engaging moiety, an E3 ligase-binding moiety, and a bridging linker. Due to their size and physicochemical complexity, these molecules do not adhere to well-established rules of lead optimization. Achieving oral bioavailability remains a key challenge in the optimization of LDDs as therapeutic agents. In this study, we build on the previously established Balanced Permeability Index (BPI) (a metric that integrates size, polarity, and lipophilicity) by incorporating an additional descriptor to account for molecular shape. Our new combined metric, termed Bifunctional Bioavailability Index (BBI), can differentiate oral bioavailability of LDDs in our data set more effectively than polarity, lipophilicity, or size separately. Notably, BBI is also more effective than <i>in vitro</i> cell permeability assays in predicting orally bioavailable LDDs. These results support the use of BBI as a computational tool for designing and optimizing bioavailable bifunctional degraders.</p>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"16 6","pages":"1108–1113 1108–1113"},"PeriodicalIF":3.5,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144261087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aleksei A Logvinov, Geert Rombouts, Matthieu Jouffroy, Steven P Nolan
{"title":"Suzuki-Miyaura Coupling of Pinacolboronic Esters Catalyzed by a Well-Defined Palladium <i>N</i>‑Heterocyclic Carbene (NHC) Catalyst.","authors":"Aleksei A Logvinov, Geert Rombouts, Matthieu Jouffroy, Steven P Nolan","doi":"10.1021/acsmedchemlett.5c00206","DOIUrl":"10.1021/acsmedchemlett.5c00206","url":null,"abstract":"<p><p>We report a versatile synthetic method for coupling heteroaryl chlorides and bromides with (hetero)-aryl pinacolboronic esters of pharmaceutical interest at low catalyst loading of a well-defined palladium-NHC catalyst providing products in good to high isolated yield and purity in short reaction time. The method displays remarkably broad applicability with both 5- and 6-membered heterocycles.</p>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"16 6","pages":"1170-1174"},"PeriodicalIF":3.5,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12169495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marta Clariano, Diogo Nunes, Daniela Canudo, Daniela Maçãs, Bruno J L Castro, Audrey Jordaan, Pedro Gomes, Anna Contini, João Perdigão, Isabel Portugal, Margarida Madureira, Digby F Warner, Marco Pieroni, Maria de Jesus Perry, Francisca Lopes
{"title":"Pyrroloquinolone-Based Compounds as a Novel Antimycobacterial Chemotype.","authors":"Marta Clariano, Diogo Nunes, Daniela Canudo, Daniela Maçãs, Bruno J L Castro, Audrey Jordaan, Pedro Gomes, Anna Contini, João Perdigão, Isabel Portugal, Margarida Madureira, Digby F Warner, Marco Pieroni, Maria de Jesus Perry, Francisca Lopes","doi":"10.1021/acsmedchemlett.5c00183","DOIUrl":"10.1021/acsmedchemlett.5c00183","url":null,"abstract":"<p><p>Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), remains the world's most lethal infectious disease, posing an uncontained health challenge. The major hurdles are the long treatments and low patient compliance that leads to the appearance of resistance, as well as the lack of drugs that effectively tackle the latent infections. Herein we report the development of compounds with the ability to target the electron transport chain of Mtb by inhibiting cytochrome <i>bcc</i> (cyt-<i>bcc</i>) (<b>7a</b>-<b>i</b>) and additionally being capable of inhibiting cytochrome <i>bd</i> (cyt-<i>bd</i>) (<b>7j</b> and <b>7k</b>). We present the synthesis, determination of physicochemical properties, evaluation of the antibacterial activity, and cytotoxicity assessment of pyrroloquinolone-based compounds. The antibacterial evaluation of <b>7a</b>-<b>k</b> showed selectivity toward mycobacteria, and the results identify cyt-<i>bcc</i> as their target. Compounds <b>7j</b> and <b>7k</b> presented promising results against Mtb and good physicochemical properties. Cytotoxicity assays revealed a good safety profile regarding the toxicity for human cell lines.</p>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"16 6","pages":"1139-1146"},"PeriodicalIF":3.5,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12169488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}