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Progress in medicinal chemistry Pub Date : 2016-02-04 DOI: 10.1016/s0079-6468(16)00010-2
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引用次数: 0
Recent Advances in the Discovery of Deubiquitinating Enzyme Inhibitors. 发现去泛素化酶抑制剂的最新进展。
Progress in medicinal chemistry Pub Date : 2016-01-01 Epub Date: 2016-01-12 DOI: 10.1016/bs.pmch.2015.10.002
Mark Kemp
{"title":"Recent Advances in the Discovery of Deubiquitinating Enzyme Inhibitors.","authors":"Mark Kemp","doi":"10.1016/bs.pmch.2015.10.002","DOIUrl":"10.1016/bs.pmch.2015.10.002","url":null,"abstract":"","PeriodicalId":20755,"journal":{"name":"Progress in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7112275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140319074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Preface. 前言。
Progress in medicinal chemistry Pub Date : 2015-01-01 DOI: 10.1016/S0079-6468(15)00009-0
Geoff Lawton, David Witty
{"title":"Preface.","authors":"Geoff Lawton, David Witty","doi":"10.1016/S0079-6468(15)00009-0","DOIUrl":"https://doi.org/10.1016/S0079-6468(15)00009-0","url":null,"abstract":"","PeriodicalId":20755,"journal":{"name":"Progress in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0079-6468(15)00009-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33092897","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
A new era for chagas disease drug discovery? 恰加斯病药物发现的新时代?
Progress in medicinal chemistry Pub Date : 2015-01-01 Epub Date: 2015-01-17 DOI: 10.1016/bs.pmch.2014.12.001
Martine Keenan, Jason H Chaplin
{"title":"A new era for chagas disease drug discovery?","authors":"Martine Keenan,&nbsp;Jason H Chaplin","doi":"10.1016/bs.pmch.2014.12.001","DOIUrl":"https://doi.org/10.1016/bs.pmch.2014.12.001","url":null,"abstract":"<p><p>Recent clinical trials investigating treatment of chronic indeterminate Chagas disease with two re-purposed azole anti-fungal drugs, posaconazole and ravuconazole, revealed their inferiority to the current standard-of-care benznidazole and highlighted the inadequacy of the existing pre-clinical testing paradigm for this disease. A very limited number of controlled clinical trials for Chagas disease have been conducted to date. The selection of these compounds for clinical evaluation relied heavily on pre-clinical data obtained from in vitro screens and animal studies. This chapter reviews the evolution of CYP51 as a target for Trypanosoma cruzi growth inhibition and also explores the impact of clinical trial data on contemporary Chagas disease drug discovery. Advances in pre-clinical profiling assays, the current compound landscape and progress towards the identification of new drug targets to re-invigorate research are reviewed. </p>","PeriodicalId":20755,"journal":{"name":"Progress in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/bs.pmch.2014.12.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33092894","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: 37
Recent advances in cancer therapeutics. 癌症治疗的最新进展。
Progress in medicinal chemistry Pub Date : 2015-01-01 Epub Date: 2015-01-23 DOI: 10.1016/bs.pmch.2014.11.002
Nicola Chessum, Keith Jones, Elisa Pasqua, Michael Tucker
{"title":"Recent advances in cancer therapeutics.","authors":"Nicola Chessum,&nbsp;Keith Jones,&nbsp;Elisa Pasqua,&nbsp;Michael Tucker","doi":"10.1016/bs.pmch.2014.11.002","DOIUrl":"https://doi.org/10.1016/bs.pmch.2014.11.002","url":null,"abstract":"<p><p>In the past 20 years, cancer therapeutics has undergone a paradigm shift away from the traditional cytotoxic drugs towards the targeting of proteins intimately involved in driving the cancer phenotype. The poster child for this alternative approach to the treatment of cancer is imatinib, a small-molecule kinase inhibitor designed to target chronic myeloid leukaemia driven by the BCR-ABL translocation in a defined patient population. The improvement in survival achieved by treatment of this patient cohort with imatinib is impressive. Thus, the aim is to provide efficacy but with low toxicity. The role of the medicinal chemist in oncology drug discovery is now closely aligned with the role in most other therapeutic areas with high-throughput and/or fragment-based screening, structure-based design, selectivity, pharmacokinetic optimisation and pharmacodynamic biomarker modulation, all playing a familiar part in the process. In this chapter, we selected four areas in which compounds are either approved drugs or in clinical trials. These are chaperone inhibitors, kinase inhibitors, histone deacetylase inhibitors and inhibitors of protein-protein interactions. Even within these areas, we have been selective, particularly for kinase inhibitors, and our aim has been to exemplify newer approaches and novel aspects of medicinal chemistry. </p>","PeriodicalId":20755,"journal":{"name":"Progress in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/bs.pmch.2014.11.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33092481","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: 32
Imaging in drug development. 药物开发中的成像。
Progress in medicinal chemistry Pub Date : 2015-01-01 Epub Date: 2014-11-27 DOI: 10.1016/bs.pmch.2014.10.002
James Nairne, Peter B Iveson, Andreas Meijer
{"title":"Imaging in drug development.","authors":"James Nairne,&nbsp;Peter B Iveson,&nbsp;Andreas Meijer","doi":"10.1016/bs.pmch.2014.10.002","DOIUrl":"https://doi.org/10.1016/bs.pmch.2014.10.002","url":null,"abstract":"<p><p>Imaging has played an important part in the diagnosis of disease and development of the understanding of the underlying disease mechanisms and is now poised to make an impact in the development of new pharmaceuticals. This chapter discusses the underlying technologies that make the field ready for this challenge. In particular, the potentials of magnetic resonance imaging and functional magnetic resonance imaging are outlined, including the new methods developed to provide additional information from the scans carried out. The field of nuclear medicine has seen a rapid increase in interest as advances in radiochemistry have enabled a wide range of new radiotracers to be synthesised. </p>","PeriodicalId":20755,"journal":{"name":"Progress in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/bs.pmch.2014.10.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33092896","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: 11
Fluorine in medicinal chemistry. 药物化学中的氟。
Progress in medicinal chemistry Pub Date : 2015-01-01 Epub Date: 2015-01-07 DOI: 10.1016/bs.pmch.2014.11.001
Steven Swallow
{"title":"Fluorine in medicinal chemistry.","authors":"Steven Swallow","doi":"10.1016/bs.pmch.2014.11.001","DOIUrl":"https://doi.org/10.1016/bs.pmch.2014.11.001","url":null,"abstract":"<p><p>Since its first use in the steroid field in the late 1950s, the use of fluorine in medicinal chemistry has become commonplace, with the small electronegative fluorine atom being a key part of the medicinal chemist's repertoire of substitutions used to modulate all aspects of molecular properties including potency, physical chemistry and pharmacokinetics. This review will highlight the special nature of fluorine, drawing from a survey of marketed fluorinated pharmaceuticals and the medicinal chemistry literature, to illustrate key concepts exploited by medicinal chemists in their attempts to optimize drug molecules. Some of the potential pitfalls in the use of fluorine will also be highlighted. </p>","PeriodicalId":20755,"journal":{"name":"Progress in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/bs.pmch.2014.11.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33092482","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: 564
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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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
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