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El. knyga: Progress in Medicinal Chemistry

Series edited by (St. Ippolyts, Herts, UK), Series edited by (WITNET LTD, Cambridge, UK)
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Progress in Medicinal Chemistry provides a review of eclectic developments in medicinal chemistry. This volume continues in the serial's tradition of providing an insight into the skills required of the modern medicinal chemist; in particular, the use of an appropriate selection of the wide range of tools now available to solve key scientific problems, including g-secretase modulators, P2X7 antagonists as therapeutic agents for CNS disorders, N-type calcium channel modulators for the treatment of pain, and more.
      • Extended timely reviews of topics in medicinal chemistry
      • Targets and technologies relevant to the discovery of tomorrow’s drugs.
      • Analyses of successful drug discovery programmes

    Daugiau informacijos

    Progress in Medicinal Chemistry provides a review of eclectic developments in medicinal chemistry. Authoritative extended reviews of targets and technologies addressing new therapeutics
    Preface v
    Contributors ix
    1 Structure-Based Drug Design for G Protein-Coupled Receptors
    1(64)
    Miles Congreve
    Joao M. Dias
    Fiona H. Marshall
    1 Introduction
    1(2)
    2 Structural Architecture of GPCRs
    3(28)
    3 GPCR Protein--Ligand X-Ray Structures
    31(4)
    4 Mechanisms of Activation: Agonist Bound Structures
    35(4)
    5 Biased Agonism
    39(1)
    6 Traditional Approaches to GPCR Drug Discovery and the Need for Change
    40(1)
    7 Potential of SBDD and FBDD for GPCR Drug Discovery
    41(13)
    8 Conclusions and Outlook
    54(11)
    Acknowledgments
    55(1)
    References
    55(10)
    2 P2X7 Antagonists as Potential Therapeutic Agents for the Treatment of CNS Disorders
    65(36)
    Christa C. Chrovian
    Jason C. Rech
    Anindya Bhattacharya
    Michael A. Letavic
    1 Introduction
    65(1)
    2 P2X7 in the CNS
    66(4)
    3 P2X7 Modulators in Clinical Trials
    70(2)
    4 P2X7 Receptor Antagonists
    72(21)
    5 Conclusion
    93(8)
    References
    93(8)
    3 γ-Secretase Modulators: Current Status and Future Directions
    101(46)
    Adrian Hall
    Toshal R. Patel
    1 Introduction
    101(3)
    2 GSMs: Chemical Classes
    104(28)
    3 Chemical Biology
    132(3)
    4 Outlook
    135(2)
    5 Clinical Studies
    137(2)
    6 Conclusions
    139(8)
    References
    140(7)
    4 Recent Progress in the Discovery and Development of N-Type Calcium Channel Modulators for the Treatment of Pain
    147(40)
    Margaret S. Lee
    1 Introduction
    147(1)
    2 Voltage-Gated Calcium Channels
    148(8)
    3 N-Type Calcium Channels
    156(3)
    4 N-Type Clinical Landscape and Emerging Pipeline
    159(19)
    5 Concluding Remarks
    178(9)
    References
    179(8)
    Subject Index 187(4)
    Cumulative Index of Authors for Volumes 1--53 191(6)
    Cumulative Index of Subjects for Volumes 1--53 197
    Dr Geoff Lawton has extensive experience in new medicine discovery across many therapeutic areas in both large and small companies and is a co-inventor of a marketed drug (Cilazapril). He is a former Director of Chemistry at Roche UK, and Vice-president Chemistry and Preclinical Sciences within Roche Bioscience, Palo Alto, USA. He was for five years the research member of a global therapy area strategy planning team for inflammatory diseases, aligning research with the clinical development and marketing parts of the business.From 2003 to 2007 he was founding Research Director with Lectus Therapeutics building from start-up a drug discovery organisation; generating the team, facilities and project portfolio targeting the next generation of ion channel modulating medicines. Since 2001 Geoff has provided scientific and strategic evaluation and advice on drug discovery as an independent consultant for a number small and medium sized biotech companies, CROs, VCs, academic groups and medical research charities. Geoff serves on the Board of Antabio, a French biotech company developing tomorrows antibacterial drugs.He is a founder of INMedD, a new medicines discovery social enterprise. Dr David Witty has more than 20 years experience in the pharmaceutical industry as a medicinal chemist and project leader working principally in areas of anti-infectives, metabolic diseases, cognition and pain, delivering clinical candidates for several conditions. He led IT Strategy within the Neurology division of GSK, developing and deploying the first Electronic Notebooks for drug discovery to sites in the UK and Singapore. He has contributed more than 90 scientific papers, reviews, patents and books on medicinal and synthetic chemistry.In 2010 David and several colleagues successfully raised $35M in venture funding to found Convergence Pharmaceuticals, a specialist ion channel company focused on the development of novel treatments for pain, based in Cambridge UK. David presently leads their discovery programme and manages scientific operations within the business.David is chairman of the Fine Chemicals Group of the Society of Chemical Industry, with responsibility for the delivery of conferences, seminars and training courses for chemists throughout the UK and Europe, and advising parliamentary bodies on matters of relevance to the UK chemical industry.Since 2008 David has been a STEM ambassador for SETPOINT, introducing school students at both primary and secondary level to the excitement and possibilities of pursuing scientific careers, through workshops, lectures and competitions.