ACS Medicinal Chemistry Letters最新文献

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Novel Indole Derivatives as Serotonergic Psychedelic Agents for Treating Psychosis, Mental Illness, and CNS Disorders 新型吲哚衍生物作为5 -羟色胺能致幻剂用于治疗精神病、精神疾病和中枢神经系统障碍
IF 3.5 3区 医学
ACS Medicinal Chemistry Letters Pub Date : 2025-05-29 DOI: 10.1021/acsmedchemlett.5c0030910.1021/acsmedchemlett.5c00309
Ram W. Sabnis*, 
{"title":"Novel Indole Derivatives as Serotonergic Psychedelic Agents for Treating Psychosis, Mental Illness, and CNS Disorders","authors":"Ram W. Sabnis*,&nbsp;","doi":"10.1021/acsmedchemlett.5c0030910.1021/acsmedchemlett.5c00309","DOIUrl":"https://doi.org/10.1021/acsmedchemlett.5c00309https://doi.org/10.1021/acsmedchemlett.5c00309","url":null,"abstract":"<p >Provided herein are novel indole derivatives as serotonergic psychedelic agents, pharmaceutical compositions, use of such compounds in treating psychosis, mental illness and central nervous system (CNS) disorders, and processes for preparing such compounds.</p>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"16 6","pages":"982–983 982–983"},"PeriodicalIF":3.5,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144260992","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
Synthesis and Application of Novel Arginine Vasopressin Receptor 1A (AVPR1A) Antagonists. 新型精氨酸抗利尿激素受体1A (AVPR1A)拮抗剂的合成与应用
IF 3.5 3区 医学
ACS Medicinal Chemistry Letters Pub Date : 2025-05-29 eCollection Date: 2025-06-12 DOI: 10.1021/acsmedchemlett.5c00285
Xin Zhou, Steven H Liang
{"title":"Synthesis and Application of Novel Arginine Vasopressin Receptor 1A (AVPR1A) Antagonists.","authors":"Xin Zhou, Steven H Liang","doi":"10.1021/acsmedchemlett.5c00285","DOIUrl":"10.1021/acsmedchemlett.5c00285","url":null,"abstract":"<p><p>Arginine Vasopressin Receptor 1A (AVPR1A) is a member of G-protein-coupled receptors (GPCRs) that binds arginine vasopressin (AVP) and is primarily related to cardiovascular function, glycogenolysis, and social behaviors. This patent describes the synthesis of a series of AVPR1A antagonists and their applications in related disease treatment.</p>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"16 6","pages":"963-964"},"PeriodicalIF":3.5,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12169450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315549","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
Deuterated 1,3 Dihydro‑2H‑indole-2-one Derivatives for Treatment of Depression or Anxiety. 氘化1,3二氢- 2H -吲哚-2- 1衍生物用于治疗抑郁或焦虑。
IF 3.5 3区 医学
ACS Medicinal Chemistry Letters Pub Date : 2025-05-28 eCollection Date: 2025-06-12 DOI: 10.1021/acsmedchemlett.5c00284
Qi-Long Hu, Steven H Liang
{"title":"Deuterated 1,3 Dihydro‑2<i>H</i>‑indole-2-one Derivatives for Treatment of Depression or Anxiety.","authors":"Qi-Long Hu, Steven H Liang","doi":"10.1021/acsmedchemlett.5c00284","DOIUrl":"10.1021/acsmedchemlett.5c00284","url":null,"abstract":"<p><p>This patent application discloses a series of l,3-dihydro-2<i>H</i>-indol-2-one derivatives targeting the vasopressin 1b receptor (V<sub>1b</sub>) or both the V<sub>1a</sub> and V<sub>1b</sub> receptors, as represented by Formula I. These vasopressin receptor antagonists exhibit significant therapeutic potential, particularly for the treatment of depression or anxiety, and hold promises for benefiting patients with reduced dosing frequency.</p>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"16 6","pages":"965-966"},"PeriodicalIF":3.5,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12169600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315513","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 Tetrahydrocyclohepteneindole Derivatives Targeting Estrogen Receptor Alpha for the Treatment of Breast Cancer. 靶向雌激素受体α的新型四氢环庚烯吲哚衍生物治疗乳腺癌。
IF 3.5 3区 医学
ACS Medicinal Chemistry Letters Pub Date : 2025-05-28 eCollection Date: 2025-06-12 DOI: 10.1021/acsmedchemlett.5c00283
Zhendong Song, Steven H Liang
{"title":"Novel Tetrahydrocyclohepteneindole Derivatives Targeting Estrogen Receptor Alpha for the Treatment of Breast Cancer.","authors":"Zhendong Song, Steven H Liang","doi":"10.1021/acsmedchemlett.5c00283","DOIUrl":"10.1021/acsmedchemlett.5c00283","url":null,"abstract":"<p><p>This patent presents novel substituted tetrahydrocyclohepteneindole derivatives as selective estrogen receptor alpha (ERα) inhibitors. These compounds demonstrate potential for treating Erα-related diseases such as cancers, ovulatory dysfunction, endometriosis, and inflammation diseases.</p>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"16 6","pages":"967-969"},"PeriodicalIF":3.5,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12169604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315539","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
Discovery of Indole-Based PDE5 Inhibitors: Synthesis and Pharmacological Evaluation. 吲哚类PDE5抑制剂的发现:合成和药理评价。
IF 3.5 3区 医学
ACS Medicinal Chemistry Letters Pub Date : 2025-05-28 eCollection Date: 2025-06-12 DOI: 10.1021/acsmedchemlett.5c00108
Shin-Young Park, Dang Pham, Param Shukla, Justin Edward, Reshmi John, Addison Li, Michael Hadjiargyrou, Mattia Mori, Elisa Zuccarello, Ottavio Arancio, Jole Fiorito
{"title":"Discovery of Indole-Based PDE5 Inhibitors: Synthesis and Pharmacological Evaluation.","authors":"Shin-Young Park, Dang Pham, Param Shukla, Justin Edward, Reshmi John, Addison Li, Michael Hadjiargyrou, Mattia Mori, Elisa Zuccarello, Ottavio Arancio, Jole Fiorito","doi":"10.1021/acsmedchemlett.5c00108","DOIUrl":"10.1021/acsmedchemlett.5c00108","url":null,"abstract":"<p><p>Phosphodiesterase 5 (PDE5) inhibitors have been suggested as new treatments for Alzheimer's disease (AD) and other conditions such as cancer and cardiovascular diseases. Utilizing the widespread presence of the indole moiety in biomolecules and drugs, previously synthesized quinoline and naphthyridine compounds were modified into novel indole-containing PDE5 inhibitors. Replacing the amine with an amide group led to identifying a potent analogue, compound <b>14a</b>, with an IC<sub>50</sub> of 16.11 nM. Molecular docking simulations further highlight the significance of the amide group in drug-target interactions. A cytotoxicity test and a parallel artificial membrane permeability assay validated the compound's potential as a lead for further drug development. Compound <b>14a</b> was shown to be safe and blood-brain barrier permeable. The discovery of these indole-containing PDE5 inhibitors provides new perspectives for developing PDE5 therapeutics.</p>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"16 6","pages":"1058-1065"},"PeriodicalIF":3.5,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12169455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315518","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
Deuterated 1,3 Dihydro-2H-indole-2-one Derivatives for Treatment of Depression or Anxiety 氘化1,3二氢- 2h -吲哚-2- 1衍生物治疗抑郁或焦虑
IF 3.5 3区 医学
ACS Medicinal Chemistry Letters Pub Date : 2025-05-28 DOI: 10.1021/acsmedchemlett.5c0028410.1021/acsmedchemlett.5c00284
Qi-Long Hu,  and , Steven H. Liang*, 
{"title":"Deuterated 1,3 Dihydro-2H-indole-2-one Derivatives for Treatment of Depression or Anxiety","authors":"Qi-Long Hu,&nbsp; and ,&nbsp;Steven H. Liang*,&nbsp;","doi":"10.1021/acsmedchemlett.5c0028410.1021/acsmedchemlett.5c00284","DOIUrl":"https://doi.org/10.1021/acsmedchemlett.5c00284https://doi.org/10.1021/acsmedchemlett.5c00284","url":null,"abstract":"<p >This patent application discloses a series of l,3-dihydro-2<i>H</i>-indol-2-one derivatives targeting the vasopressin 1b receptor (V<sub>1b</sub>) or both the V<sub>1a</sub> and V<sub>1b</sub> receptors, as represented by Formula I. These vasopressin receptor antagonists exhibit significant therapeutic potential, particularly for the treatment of depression or anxiety, and hold promises for benefiting patients with reduced dosing frequency.</p>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"16 6","pages":"965–966 965–966"},"PeriodicalIF":3.5,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144261205","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 Tetrahydrocyclohepteneindole Derivatives Targeting Estrogen Receptor Alpha for the Treatment of Breast Cancer 靶向雌激素受体α的新型四氢环庚烯吲哚衍生物治疗乳腺癌
IF 3.5 3区 医学
ACS Medicinal Chemistry Letters Pub Date : 2025-05-28 DOI: 10.1021/acsmedchemlett.5c0028310.1021/acsmedchemlett.5c00283
Zhendong Song,  and , Steven H. Liang*, 
{"title":"Novel Tetrahydrocyclohepteneindole Derivatives Targeting Estrogen Receptor Alpha for the Treatment of Breast Cancer","authors":"Zhendong Song,&nbsp; and ,&nbsp;Steven H. Liang*,&nbsp;","doi":"10.1021/acsmedchemlett.5c0028310.1021/acsmedchemlett.5c00283","DOIUrl":"https://doi.org/10.1021/acsmedchemlett.5c00283https://doi.org/10.1021/acsmedchemlett.5c00283","url":null,"abstract":"<p >This patent presents novel substituted tetrahydrocyclohepteneindole derivatives as selective estrogen receptor alpha (ERα) inhibitors. These compounds demonstrate potential for treating Erα-related diseases such as cancers, ovulatory dysfunction, endometriosis, and inflammation diseases.</p>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"16 6","pages":"967–969 967–969"},"PeriodicalIF":3.5,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144261224","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
Discovery of Indole-Based PDE5 Inhibitors: Synthesis and Pharmacological Evaluation 吲哚类PDE5抑制剂的发现:合成和药理评价
IF 3.5 3区 医学
ACS Medicinal Chemistry Letters Pub Date : 2025-05-27 DOI: 10.1021/acsmedchemlett.5c0010810.1021/acsmedchemlett.5c00108
Shin-Young Park, Dang Pham, Param Shukla, Justin Edward, Reshmi John, Addison Li, Michael Hadjiargyrou, Mattia Mori, Elisa Zuccarello, Ottavio Arancio and Jole Fiorito*, 
{"title":"Discovery of Indole-Based PDE5 Inhibitors: Synthesis and Pharmacological Evaluation","authors":"Shin-Young Park,&nbsp;Dang Pham,&nbsp;Param Shukla,&nbsp;Justin Edward,&nbsp;Reshmi John,&nbsp;Addison Li,&nbsp;Michael Hadjiargyrou,&nbsp;Mattia Mori,&nbsp;Elisa Zuccarello,&nbsp;Ottavio Arancio and Jole Fiorito*,&nbsp;","doi":"10.1021/acsmedchemlett.5c0010810.1021/acsmedchemlett.5c00108","DOIUrl":"https://doi.org/10.1021/acsmedchemlett.5c00108https://doi.org/10.1021/acsmedchemlett.5c00108","url":null,"abstract":"<p >Phosphodiesterase 5 (PDE5) inhibitors have been suggested as new treatments for Alzheimer’s disease (AD) and other conditions such as cancer and cardiovascular diseases. Utilizing the widespread presence of the indole moiety in biomolecules and drugs, previously synthesized quinoline and naphthyridine compounds were modified into novel indole-containing PDE5 inhibitors. Replacing the amine with an amide group led to identifying a potent analogue, compound <b>14a</b>, with an IC<sub>50</sub> of 16.11 nM. Molecular docking simulations further highlight the significance of the amide group in drug-target interactions. A cytotoxicity test and a parallel artificial membrane permeability assay validated the compound’s potential as a lead for further drug development. Compound <b>14a</b> was shown to be safe and blood-brain barrier permeable. The discovery of these indole-containing PDE5 inhibitors provides new perspectives for developing PDE5 therapeutics.</p>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"16 6","pages":"1058–1065 1058–1065"},"PeriodicalIF":3.5,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acsmedchemlett.5c00108","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144261221","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
Benzosuberene and Tetracyclic Analogues as Colchicine Site Inhibitors of Tubulin Polymerization. 苯并亚苯胺和四环类似物作为微管蛋白聚合的秋水仙碱位点抑制剂。
IF 3.5 3区 医学
ACS Medicinal Chemistry Letters Pub Date : 2025-05-26 eCollection Date: 2025-06-12 DOI: 10.1021/acsmedchemlett.5c00129
Jennifer M VanNatta, Graham J Carlson, Haichan Niu, Ruoli Bai, Hashini I Wanniarachchi, Regan Schuetze, Mary Lynn Trawick, Ernest Hamel, Ralph P Mason, Kevin G Pinney
{"title":"Benzosuberene and Tetracyclic Analogues as Colchicine Site Inhibitors of Tubulin Polymerization.","authors":"Jennifer M VanNatta, Graham J Carlson, Haichan Niu, Ruoli Bai, Hashini I Wanniarachchi, Regan Schuetze, Mary Lynn Trawick, Ernest Hamel, Ralph P Mason, Kevin G Pinney","doi":"10.1021/acsmedchemlett.5c00129","DOIUrl":"10.1021/acsmedchemlett.5c00129","url":null,"abstract":"<p><p>Colchicine site inhibitors of tubulin polymerization function as antiproliferative anticancer agents, with certain inhibitors demonstrating a dual mechanism of action as tumor-selective vascular disrupting agents (VDAs). Our previous studies yielded potent benzosuberene-based colchicine site inhibitors of tubulin polymerization. To expand structure-activity correlations, the seven-membered fused ring and the pendant ring were modified to generate a series of new compounds, 11 being strong inhibitors (IC<sub>50</sub> ≤ 5 μM) of tubulin polymerization. Structural modifications introduced a second benzylic olefin and, separately, a nitrogen atom to the fused seven-membered ring, along with conversion to unique tetracyclic fused ring systems. Two of the active inhibitors were synthetically converted to corresponding phosphate prodrug salts to increase aqueous solubility for <i>in vivo</i> studies. In a preliminary study of VDA efficacy, these prodrugs caused blood flow disruption in mice, as revealed by bioluminescence imaging with histological confirmation. The most effective analogues from this series offer promise as cancer therapeutic agents.</p>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"16 6","pages":"1098-1107"},"PeriodicalIF":3.5,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12169467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315510","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
Benzosuberene and Tetracyclic Analogues as Colchicine Site Inhibitors of Tubulin Polymerization 苯并亚苯胺和四环类似物作为微管蛋白聚合的秋水仙碱位点抑制剂
IF 3.5 3区 医学
ACS Medicinal Chemistry Letters Pub Date : 2025-05-26 DOI: 10.1021/acsmedchemlett.5c0012910.1021/acsmedchemlett.5c00129
Jennifer M. VanNatta, Graham J. Carlson, Haichan Niu, Ruoli Bai, Hashini I. Wanniarachchi, Regan Schuetze, Mary Lynn Trawick, Ernest Hamel, Ralph P. Mason and Kevin G. Pinney*, 
{"title":"Benzosuberene and Tetracyclic Analogues as Colchicine Site Inhibitors of Tubulin Polymerization","authors":"Jennifer M. VanNatta,&nbsp;Graham J. Carlson,&nbsp;Haichan Niu,&nbsp;Ruoli Bai,&nbsp;Hashini I. Wanniarachchi,&nbsp;Regan Schuetze,&nbsp;Mary Lynn Trawick,&nbsp;Ernest Hamel,&nbsp;Ralph P. Mason and Kevin G. Pinney*,&nbsp;","doi":"10.1021/acsmedchemlett.5c0012910.1021/acsmedchemlett.5c00129","DOIUrl":"https://doi.org/10.1021/acsmedchemlett.5c00129https://doi.org/10.1021/acsmedchemlett.5c00129","url":null,"abstract":"<p >Colchicine site inhibitors of tubulin polymerization function as antiproliferative anticancer agents, with certain inhibitors demonstrating a dual mechanism of action as tumor-selective vascular disrupting agents (VDAs). Our previous studies yielded potent benzosuberene-based colchicine site inhibitors of tubulin polymerization. To expand structure–activity correlations, the seven-membered fused ring and the pendant ring were modified to generate a series of new compounds, 11 being strong inhibitors (IC<sub>50</sub> ≤ 5 μM) of tubulin polymerization. Structural modifications introduced a second benzylic olefin and, separately, a nitrogen atom to the fused seven-membered ring, along with conversion to unique tetracyclic fused ring systems. Two of the active inhibitors were synthetically converted to corresponding phosphate prodrug salts to increase aqueous solubility for <i>in vivo</i> studies. In a preliminary study of VDA efficacy, these prodrugs caused blood flow disruption in mice, as revealed by bioluminescence imaging with histological confirmation. The most effective analogues from this series offer promise as cancer therapeutic agents.</p>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"16 6","pages":"1098–1107 1098–1107"},"PeriodicalIF":3.5,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144261132","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
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