Springer Theses

Development of Novel Anti-HIV Pyrimidobenzothiazine Derivatives

Authors: Mizuhara, Tsukasa

  • Nominated by Kyoto University as an outstanding Ph.D. thesis
  • Divergent synthetic methods that enable efficient structure–activity relationship studies
  • Development of more potent derivatives based on extensive structure-activity relationship studies
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  • ISBN 978-4-431-54445-6
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Hardcover $99.00
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  • ISBN 978-4-431-54444-9
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Softcover $99.00
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  • Due: October 7, 2016
  • ISBN 978-4-431-56165-1
  • Free shipping for individuals worldwide
About this book

The author successfully developed novel anti-HIV PD 404182 derivatives that exhibited submicromolar inhibitory activity against both HIV-1 and HIV-2. His thesis is in three parts. The first part expounds efficient methods for the synthesis of tricyclic heterocycles related to PD 404182 based on the sp2-carbon−heteroatom bond formations. Starting from arene or haloarene, C-O, C-N, or C-S bonds were formed by simply changing the reactants. These synthetic methods provide powerful approaches for the divergent preparation of pyrimido-benzoxazine, -quinazoline, or -benzothiazine derivatives. The second part explains SAR studies of PD 404182 for the development of anti-HIV agents. Through optimization studies of the central 1,3-thiazin-2-imine core, the benzene and cyclic amidine ring parts, 3-fold more potent inhibitors were obtained compared with the lead compound. The author also reveals by a time-of-drug-addition experiment that PD 404182 derivatives impaired HIV replication at the binding or fusion stage. The third part of the thesis elucidates the development of photoaffinity probes for the target identification of PD 404182. By the photolabeling experiment of HIV-1-infected H9 cells using these probes, the author detected proteins specifically bound to PD 404182. These new anti-HIV agents may be promising agents for anti-HIV therapy because their mechanisms of action differ from those of the currently approved anti-HIV agents.

About the authors

Department of Chemistry

University of Massachusetts Amherst, USA

Ph. D. in Pharmaceutical Sciences

Graduate School of Pharmaceutical Sciences,

Kyoto University, Japan

Table of contents (5 chapters)

  • Introduction

    Mizuhara, Tsukasa

    Pages 1-5

  • Development of Divergent Synthetic Methods of Pyrimidobenzothiazine and Related Tricyclic Heterocycles

    Mizuhara, Tsukasa

    Pages 7-39

  • Structure–Activity Relationship Study of PD 404182 Derivatives for the Highly Potent Anti-HIV Agents

    Mizuhara, Tsukasa

    Pages 41-127

  • Design and Synthesis of Photoaffinity Probes and Their Application to Target Identification Study of PD 404182

    Mizuhara, Tsukasa

    Pages 129-146

  • Conclusions

    Mizuhara, Tsukasa

    Pages 147-147

Buy this book

eBook $74.99
price for USA (gross)
  • ISBN 978-4-431-54445-6
  • Digitally watermarked, DRM-free
  • Included format: EPUB, PDF
  • ebooks can be used on all reading devices
  • Immediate eBook download after purchase
Hardcover $99.00
price for USA
  • ISBN 978-4-431-54444-9
  • Free shipping for individuals worldwide
  • Usually dispatched within 3 to 5 business days.
Softcover $99.00
price for USA
  • Customers within the U.S. and Canada please contact Customer Service at 1-800-777-4643, Latin America please contact us at +1-212-460-1500 (Weekdays 8:30am – 5:30pm ET) to place your order.
  • Due: October 7, 2016
  • ISBN 978-4-431-56165-1
  • Free shipping for individuals worldwide
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Bibliographic Information

Bibliographic Information
Book Title
Development of Novel Anti-HIV Pyrimidobenzothiazine Derivatives
Authors
Series Title
Springer Theses
Copyright
2013
Publisher
Springer Japan
Copyright Holder
Springer Japan
eBook ISBN
978-4-431-54445-6
DOI
10.1007/978-4-431-54445-6
Hardcover ISBN
978-4-431-54444-9
Softcover ISBN
978-4-431-56165-1
Series ISSN
2190-5053
Edition Number
1
Number of Pages
XI, 151
Number of Illustrations and Tables
95 b/w illustrations, 3 illustrations in colour
Topics