Overview
- 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
Part of the book series: Springer Theses (Springer Theses)
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Table of contents (5 chapters)
Keywords
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.
Authors and Affiliations
About the author
Department of Chemistry
University of Massachusetts Amherst, USA
Ph. D. in Pharmaceutical Sciences
Graduate School of Pharmaceutical Sciences,
Kyoto University, Japan
Bibliographic Information
Book Title: Development of Novel Anti-HIV Pyrimidobenzothiazine Derivatives
Authors: Tsukasa Mizuhara
Series Title: Springer Theses
DOI: https://doi.org/10.1007/978-4-431-54445-6
Publisher: Springer Tokyo
eBook Packages: Chemistry and Materials Science, Chemistry and Material Science (R0)
Copyright Information: Springer Japan 2013
Hardcover ISBN: 978-4-431-54444-9Published: 17 October 2013
Softcover ISBN: 978-4-431-56165-1Published: 23 August 2016
eBook ISBN: 978-4-431-54445-6Published: 07 October 2013
Series ISSN: 2190-5053
Series E-ISSN: 2190-5061
Edition Number: 1
Number of Pages: XI, 151
Number of Illustrations: 95 b/w illustrations, 3 illustrations in colour
Topics: Organic Chemistry, Pharmaceutical Sciences/Technology, Medicinal Chemistry, Virology