ACS Medicinal Chemistry Letters最新文献_第4页

Novel Triazine Derivatives as NLRP3 Inhibitors for Treating Asthma or COPD.

IF 3.5 3区医学

ACS Medicinal Chemistry Letters Pub Date : 2025-01-24 eCollection Date: 2025-02-13 DOI: 10.1021/acsmedchemlett.5c00020

Ram W Sabnis

引用次数: 0

Integrating Artificial Intelligence and Digital Innovations in Psychedelic and Brain Therapeutics

IF 3.5 3区医学

ACS Medicinal Chemistry Letters Pub Date : 2025-01-23 DOI: 10.1021/acsmedchemlett.5c0002910.1021/acsmedchemlett.5c00029

Robert B. Kargbo*,

引用次数: 0

Novel Indoline Derivatives as Serotonergic Psychedelic Agents for Treating Psychosis, Mental Illness and CNS Disorders

IF 3.5 3区医学

ACS Medicinal Chemistry Letters Pub Date : 2025-01-23 DOI: 10.1021/acsmedchemlett.5c0000410.1021/acsmedchemlett.5c00004

Ram W. Sabnis*, and , Anika R. Sabnis,

引用次数: 0

Integrating Artificial Intelligence and Digital Innovations in Psychedelic and Brain Therapeutics.

IF 3.5 3区医学

ACS Medicinal Chemistry Letters Pub Date : 2025-01-23 eCollection Date: 2025-02-13 DOI: 10.1021/acsmedchemlett.5c00029

Robert B Kargbo

引用次数: 0

Novel Pyrrolopyridine Compounds as 5-HT2A Agonists for Treating Mental Illnesses.

IF 3.5 3区医学

ACS Medicinal Chemistry Letters Pub Date : 2025-01-23 eCollection Date: 2025-02-13 DOI: 10.1021/acsmedchemlett.5c00019

Ram W Sabnis, Anika R Sabnis

引用次数: 0

Novel Pyrrolopyridine Compounds as 5-HT2A Agonists for Treating Mental Illnesses

IF 3.5 3区医学

ACS Medicinal Chemistry Letters Pub Date : 2025-01-23 DOI: 10.1021/acsmedchemlett.5c0001910.1021/acsmedchemlett.5c00019

Ram W. Sabnis*, and , Anika R. Sabnis,

引用次数: 0

Novel Cyclohexyl Amido Acid Antagonists of Lysophosphatidic Acid Type 1 Receptor for the Treatment of Pulmonary Fibrosis.

IF 3.5 3区医学

ACS Medicinal Chemistry Letters Pub Date : 2025-01-23 eCollection Date: 2025-02-13 DOI: 10.1021/acsmedchemlett.4c00559

Marta Giuliani, Andrea Rizzi, Mafalda Pagano, Luca F Raveglia, Francesca Saccani, Maria Rosaria Di Lascia, Margherita Interlandi, Tonia Simona Nardella, Gessica Marchini, Annalisa Murgo, Laura Tigli, Alice Pappani, Anna Maria Capelli, Sergio Xanxo Fernandez, Paola Puccini, Gino Villetti, Maurizio Civelli, Claudia Beato, Elisa Moro, Claudia Mundi, Rosaria Remelli, Elisabetta Armani

{"title":"Novel Cyclohexyl Amido Acid Antagonists of Lysophosphatidic Acid Type 1 Receptor for the Treatment of Pulmonary Fibrosis.","authors":"Marta Giuliani, Andrea Rizzi, Mafalda Pagano, Luca F Raveglia, Francesca Saccani, Maria Rosaria Di Lascia, Margherita Interlandi, Tonia Simona Nardella, Gessica Marchini, Annalisa Murgo, Laura Tigli, Alice Pappani, Anna Maria Capelli, Sergio Xanxo Fernandez, Paola Puccini, Gino Villetti, Maurizio Civelli, Claudia Beato, Elisa Moro, Claudia Mundi, Rosaria Remelli, Elisabetta Armani","doi":"10.1021/acsmedchemlett.4c00559","DOIUrl":"10.1021/acsmedchemlett.4c00559","url":null,"abstract":"Lysophosphatidic acid (LPA) is a phospholipid activating different biological functions by binding to G protein-coupled receptors (LPA1-6). Among these, the role of the LPA1 receptor in modulating fibrotic processes is well-known, making it a therapeutic target for pulmonary fibrosis and other fibrotic disorders. Herein we report the search for a new class of LPA1 antagonists for the oral treatment of idiopathic pulmonary fibrosis with a focus on hepatobiliary safety. Compound 7 excelled in in vitro and in vivo efficacy, showing significant efficacy both in PD studies and in a rodent lung fibrosis model, with a promising in vitro hepatic safety profile. However, in a dose range finding (DRF) toxicity study, compound 7 did not ensure safety regarding potential hepatobiliary toxicity, leading to its development being halted.","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"16 2","pages":"317-326"},"PeriodicalIF":3.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11831564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447403","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}

引用次数: 0

Novel Cyclohexyl Amido Acid Antagonists of Lysophosphatidic Acid Type 1 Receptor for the Treatment of Pulmonary Fibrosis

IF 3.5 3区医学

ACS Medicinal Chemistry Letters Pub Date : 2025-01-23 DOI: 10.1021/acsmedchemlett.4c0055910.1021/acsmedchemlett.4c00559

Marta Giuliani*, Andrea Rizzi, Mafalda Pagano, Luca F. Raveglia, Francesca Saccani, Maria Rosaria Di Lascia, Margherita Interlandi, Tonia Simona Nardella, Gessica Marchini, Annalisa Murgo, Laura Tigli, Alice Pappani, Anna Maria Capelli, Sergio Xanxo Fernandez, Paola Puccini, Gino Villetti, Maurizio Civelli, Claudia Beato, Elisa Moro, Claudia Mundi, Rosaria Remelli and Elisabetta Armani*,

{"title":"Novel Cyclohexyl Amido Acid Antagonists of Lysophosphatidic Acid Type 1 Receptor for the Treatment of Pulmonary Fibrosis","authors":"Marta Giuliani*, Andrea Rizzi, Mafalda Pagano, Luca F. Raveglia, Francesca Saccani, Maria Rosaria Di Lascia, Margherita Interlandi, Tonia Simona Nardella, Gessica Marchini, Annalisa Murgo, Laura Tigli, Alice Pappani, Anna Maria Capelli, Sergio Xanxo Fernandez, Paola Puccini, Gino Villetti, Maurizio Civelli, Claudia Beato, Elisa Moro, Claudia Mundi, Rosaria Remelli and Elisabetta Armani*, ","doi":"10.1021/acsmedchemlett.4c0055910.1021/acsmedchemlett.4c00559","DOIUrl":"https://doi.org/10.1021/acsmedchemlett.4c00559https://doi.org/10.1021/acsmedchemlett.4c00559","url":null,"abstract":"Lysophosphatidic acid (LPA) is a phospholipid activating different biological functions by binding to G protein-coupled receptors (LPA1–6). Among these, the role of the LPA1 receptor in modulating fibrotic processes is well-known, making it a therapeutic target for pulmonary fibrosis and other fibrotic disorders. Herein we report the search for a new class of LPA1 antagonists for the oral treatment of idiopathic pulmonary fibrosis with a focus on hepatobiliary safety. Compound 7 excelled in in vitro and in vivo efficacy, showing significant efficacy both in PD studies and in a rodent lung fibrosis model, with a promising in vitro hepatic safety profile. However, in a dose range finding (DRF) toxicity study, compound 7 did not ensure safety regarding potential hepatobiliary toxicity, leading to its development being halted.","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"16 2","pages":"317–326 317–326"},"PeriodicalIF":3.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143394126","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}

引用次数: 0

Novel Indoline Derivatives as Serotonergic Psychedelic Agents for Treating Psychosis, Mental Illness and CNS Disorders.

IF 3.5 3区医学

ACS Medicinal Chemistry Letters Pub Date : 2025-01-23 eCollection Date: 2025-02-13 DOI: 10.1021/acsmedchemlett.5c00004

Ram W Sabnis, Anika R Sabnis

引用次数: 0

Design, Synthesis, and Biological Evaluation of Chiral-Proline Derivatives as Novel HSP90 Inhibitors.

IF 3.5 3区医学

ACS Medicinal Chemistry Letters Pub Date : 2025-01-22 eCollection Date: 2025-02-13 DOI: 10.1021/acsmedchemlett.4c00550

Chao Zhang, Shuang Cui, Jialin Mu, Kexin Liu, Yuanxun Wang, Hongyu Zhao, Yuguang Mu, Youming Zhang, Xiaobo Wan, Chun Song

{"title":"Design, Synthesis, and Biological Evaluation of Chiral-Proline Derivatives as Novel HSP90 Inhibitors.","authors":"Chao Zhang, Shuang Cui, Jialin Mu, Kexin Liu, Yuanxun Wang, Hongyu Zhao, Yuguang Mu, Youming Zhang, Xiaobo Wan, Chun Song","doi":"10.1021/acsmedchemlett.4c00550","DOIUrl":"10.1021/acsmedchemlett.4c00550","url":null,"abstract":"Heat shock protein 90 (HSP90) is a promising target for oncology therapeutics. Over the past decades, several small molecule inhibitors have demonstrated significant antitumor activity in clinical trials. However, nearly all HSP90 inhibitors in clinical trials have failed due to toxicity or insufficient efficacy. By leveraging crystal structures and current knowledge, we synthesized and evaluated a series of novel derivatives with potent HSP90 inhibitory activity, optimized from resorcinol-based (2R, 4R)-4-phenylproline. These derivatives underwent SAR analysis, leading to the discovery of compounds 16t and 20m, which exhibit strong HSP90 binding affinity and antiproliferative effects against MCF-7, HCT116, SKBr3, K562, and A549 cell lines. Nevertheless, further optimization of derivatives 16t and 20m was required to enhance their oral bioavailability and isoform selectivity. Our findings provide valuable insights for the ongoing research into selective HSP90α inhibitors and lay a foundation for developing next-generation HSP90α inhibitors and antitumor agents.","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"16 2","pages":"301-310"},"PeriodicalIF":3.5,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11831383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447347","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}

引用次数: 0