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Progress in medicinal chemistry最新文献

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A perspective on the next generation of antibacterial agents derived by manipulation of natural products. 从自然产物的操纵中衍生的下一代抗菌剂的观点。
Progress in medicinal chemistry Pub Date : 2015-01-01 Epub Date: 2014-12-01 DOI: 10.1016/bs.pmch.2014.10.001
Pamela Brown, Michael J Dawson
{"title":"A perspective on the next generation of antibacterial agents derived by manipulation of natural products.","authors":"Pamela Brown,&nbsp;Michael J Dawson","doi":"10.1016/bs.pmch.2014.10.001","DOIUrl":"https://doi.org/10.1016/bs.pmch.2014.10.001","url":null,"abstract":"<p><p>Natural products have been a major source of anti-infective drugs for many decades. With urgent need for new antibacterial agents to combat drug-resistant bacteria, the investigation of both new and existing classes of natural products has once again become an important focus. In this review, we highlight how a medicinal chemistry/semi-synthetic approach to natural product manipulation continues to offer a valuable strategy to overcome limitations in current therapy. Approaches to address toxicity and to improve the solubility, bioavailability and the spectrum of activity are demonstrated. Examples are drawn from aminoglycosides, glycopeptides, tetracyclines, macrolides, thiazolyl peptides, pleuromutilins and polymyxins and are taken from the current literature, patents and abstracts of symposia. In many cases, this approach has led to drug candidates currently in late stages of clinical development. </p>","PeriodicalId":20755,"journal":{"name":"Progress in medicinal chemistry","volume":"54 ","pages":"135-84"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/bs.pmch.2014.10.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33092893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 20
Structure-based drug design for G protein-coupled receptors. 基于结构的G蛋白偶联受体药物设计。
Progress in medicinal chemistry Pub Date : 2014-01-01 DOI: 10.1016/B978-0-444-63380-4.00001-9
Miles Congreve, João M Dias, Fiona H Marshall
{"title":"Structure-based drug design for G protein-coupled receptors.","authors":"Miles Congreve,&nbsp;João M Dias,&nbsp;Fiona H Marshall","doi":"10.1016/B978-0-444-63380-4.00001-9","DOIUrl":"https://doi.org/10.1016/B978-0-444-63380-4.00001-9","url":null,"abstract":"<p><p>Our understanding of the structural biology of G protein-coupled receptors has undergone a transformation over the past 5 years. New protein-ligand complexes are described almost monthly in high profile journals. Appreciation of how small molecules and natural ligands bind to their receptors has the potential to impact enormously how medicinal chemists approach this major class of receptor targets. An outline of the key topics in this field and some recent examples of structure- and fragment-based drug design are described. A table is presented with example views of each G protein-coupled receptor for which there is a published X-ray structure, including interactions with small molecule antagonists, partial and full agonists. The possible implications of these new data for drug design are discussed. </p>","PeriodicalId":20755,"journal":{"name":"Progress in medicinal chemistry","volume":"53 ","pages":"1-63"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/B978-0-444-63380-4.00001-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32023740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 71
P2X7 antagonists as potential therapeutic agents for the treatment of CNS disorders. P2X7拮抗剂作为治疗中枢神经系统疾病的潜在治疗剂。
Progress in medicinal chemistry Pub Date : 2014-01-01 DOI: 10.1016/B978-0-444-63380-4.00002-0
Christa C Chrovian, Jason C Rech, Anindya Bhattacharya, Michael A Letavic
{"title":"P2X7 antagonists as potential therapeutic agents for the treatment of CNS disorders.","authors":"Christa C Chrovian,&nbsp;Jason C Rech,&nbsp;Anindya Bhattacharya,&nbsp;Michael A Letavic","doi":"10.1016/B978-0-444-63380-4.00002-0","DOIUrl":"https://doi.org/10.1016/B978-0-444-63380-4.00002-0","url":null,"abstract":"<p><p>The use of P2X7 antagonists to treat inflammatory disorders has garnered considerable interest in recent years. An increasing number of literature reports support the role of P2X7 in inflammatory pathways of the peripheral and central nervous systems (CNSs). A number of CNS indications such as neuropsychiatric and neurodegenerative disorders and neuropathic pain have been linked to a neuroinflammatory response, and clinical studies have shown that inflammatory biomarkers can be mitigated by modulating P2X7. Recent scientific and patent literature describing novel P2X7 antagonists has indicated their use in CNS disorders. In addition, several reports have disclosed the results of administering P2X7 antagonists in pre-clinical models of CNS disease or investigating brain uptake. This review describes small molecule P2X7 antagonists that have first appeared in the literature since 2009 and have potential therapeutic utility in the CNS, or for which new data have emerged implicating their use in CNS indications. </p>","PeriodicalId":20755,"journal":{"name":"Progress in medicinal chemistry","volume":"53 ","pages":"65-100"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/B978-0-444-63380-4.00002-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32023741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 55
Recent progress in the discovery and development of N-type calcium channel modulators for the treatment of pain. 治疗疼痛的n型钙通道调节剂的发现与开发进展。
Progress in medicinal chemistry Pub Date : 2014-01-01 DOI: 10.1016/B978-0-444-63380-4.00004-4
Margaret S Lee
{"title":"Recent progress in the discovery and development of N-type calcium channel modulators for the treatment of pain.","authors":"Margaret S Lee","doi":"10.1016/B978-0-444-63380-4.00004-4","DOIUrl":"https://doi.org/10.1016/B978-0-444-63380-4.00004-4","url":null,"abstract":"<p><p>The importance of voltage-gated calcium channels (VGCCs) in basic physiological processes such as cardiac and neurological function has generated intense interest in these proteins as targets of pharmacological intervention. N-type calcium channels are a subset of VGCCs distinguished by their physiology, pharmacology and significance to the pathology of chronic pain. Despite decades of investigation, only a single drug targeting N-type channel function has entered the marketplace. This review will summarize our current understanding of the biology, physiology and pharmacology of N-type calcium channels and the implication of these features for therapeutic intervention. From this basis of understanding, recent efforts to discover and develop peptide based and small molecule modulators of N-type calcium channel function will be discussed. </p>","PeriodicalId":20755,"journal":{"name":"Progress in medicinal chemistry","volume":"53 ","pages":"147-86"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/B978-0-444-63380-4.00004-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32023743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 25
Preface. 前言。
Progress in medicinal chemistry Pub Date : 2014-01-01 DOI: 10.1016/B978-0-444-63380-4.09989-3
Geoff Lawton, David Witty
{"title":"Preface.","authors":"Geoff Lawton,&nbsp;David Witty","doi":"10.1016/B978-0-444-63380-4.09989-3","DOIUrl":"https://doi.org/10.1016/B978-0-444-63380-4.09989-3","url":null,"abstract":"","PeriodicalId":20755,"journal":{"name":"Progress in medicinal chemistry","volume":"53 ","pages":"v-vi"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/B978-0-444-63380-4.09989-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32023744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
γ-Secretase modulators: current status and future directions. γ-分泌酶调节剂:现状及未来发展方向
Progress in medicinal chemistry Pub Date : 2014-01-01 DOI: 10.1016/B978-0-444-63380-4.00003-2
Adrian Hall, Toshal R Patel
{"title":"γ-Secretase modulators: current status and future directions.","authors":"Adrian Hall,&nbsp;Toshal R Patel","doi":"10.1016/B978-0-444-63380-4.00003-2","DOIUrl":"https://doi.org/10.1016/B978-0-444-63380-4.00003-2","url":null,"abstract":"<p><p>This chapter reviews the current status of γ-secretase modulators, highlighting key compounds by each company involved in the area. The review focuses on the three main chemotypes: acids, imidazoles and related derivatives and natural products. A section on chemical biology and ligand-binding site elucidation studies is also included. The primary source of information is drawn from peer reviewed literature as this permits analysis of PK-PD relationships and subsequent comment. Discussion of the patent literature is included for completeness. From this analysis, the key issues and challenges in the area are highlighted. The review concludes with a summary of the clinical development status and comment on future prospects of the field. </p>","PeriodicalId":20755,"journal":{"name":"Progress in medicinal chemistry","volume":"53 ","pages":"101-45"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/B978-0-444-63380-4.00003-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32023742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 45
Advances in the discovery of selective JAK inhibitors. 选择性JAK抑制剂的发现进展。
Progress in medicinal chemistry Pub Date : 2013-01-01 DOI: 10.1016/B978-0-444-62652-3.00004-1
Christel J Menet, Luc Van Rompaey, Raphaël Geney
{"title":"Advances in the discovery of selective JAK inhibitors.","authors":"Christel J Menet,&nbsp;Luc Van Rompaey,&nbsp;Raphaël Geney","doi":"10.1016/B978-0-444-62652-3.00004-1","DOIUrl":"https://doi.org/10.1016/B978-0-444-62652-3.00004-1","url":null,"abstract":"<p><p>In this review, we describe the current knowledge of the biology of the JAKs. The JAK family comprises the four nonreceptor tyrosine kinases JAK1, JAK2, JAK3, and Tyk2, all key players in the signal transduction from cytokine receptors to transcription factor activation. We also review the progresses made towards the optimization of JAK inhibitors and the importance of their selectivity profile. Indeed, the full array of many medicinal chemistry enabling tools (HTS, X-ray crystallography, scaffold morphing, etc.) has been deployed to successfully design molecules that discriminate among JAK family and other kinases. While the first JAK inhibitor was launched in 2011, this review also summarizes the status of several other small-molecule JAK inhibitors currently in development to treat arthritis, psoriasis, organ rejection, and multiple cancer types.</p>","PeriodicalId":20755,"journal":{"name":"Progress in medicinal chemistry","volume":"52 ","pages":"153-223"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/B978-0-444-62652-3.00004-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31217738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 70
Glucokinase. Preface. 葡糖激酶。前言。
Progress in medicinal chemistry Pub Date : 2013-01-01 DOI: 10.1016/B978-0-444-62652-3.10000-6
Geoff Lawton, David R Witty
{"title":"Glucokinase. Preface.","authors":"Geoff Lawton,&nbsp;David R Witty","doi":"10.1016/B978-0-444-62652-3.10000-6","DOIUrl":"https://doi.org/10.1016/B978-0-444-62652-3.10000-6","url":null,"abstract":"","PeriodicalId":20755,"journal":{"name":"Progress in medicinal chemistry","volume":"52 ","pages":"v-vii"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/B978-0-444-62652-3.10000-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31217739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Antimalarial drug discovery: recent progress and future directions. 抗疟药物的发现:最新进展和未来方向。
Progress in medicinal chemistry Pub Date : 2013-01-01 DOI: 10.1016/B978-0-444-62652-3.00003-X
Félix Calderón, David M Wilson, Francisco-Javier Gamo
{"title":"Antimalarial drug discovery: recent progress and future directions.","authors":"Félix Calderón,&nbsp;David M Wilson,&nbsp;Francisco-Javier Gamo","doi":"10.1016/B978-0-444-62652-3.00003-X","DOIUrl":"https://doi.org/10.1016/B978-0-444-62652-3.00003-X","url":null,"abstract":"","PeriodicalId":20755,"journal":{"name":"Progress in medicinal chemistry","volume":"52 ","pages":"97-151"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/B978-0-444-62652-3.00003-X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31217737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 31
Medicinal chemistry of glucagon-like peptide receptor agonists. 胰高血糖素样肽受体激动剂的药物化学。
Progress in medicinal chemistry Pub Date : 2013-01-01 DOI: 10.1016/B978-0-444-62652-3.00002-8
Lyn H Jones, David A Price
{"title":"Medicinal chemistry of glucagon-like peptide receptor agonists.","authors":"Lyn H Jones,&nbsp;David A Price","doi":"10.1016/B978-0-444-62652-3.00002-8","DOIUrl":"https://doi.org/10.1016/B978-0-444-62652-3.00002-8","url":null,"abstract":"","PeriodicalId":20755,"journal":{"name":"Progress in medicinal chemistry","volume":"52 ","pages":"45-96"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/B978-0-444-62652-3.00002-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31217736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 12
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