Development Of Novel Anti Hiv Pyrimidobenzothiazine Derivatives

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.

This topical reference and handbook addresses the chemistry, pharmacology, toxicology and the patentability of prodrugs, perfectly mirroring the integrated approach prevalent in today's drug design. It summarizes current experiences and strategies for the rational design of prodrugs, beginning at the early stages of the development process, as well as discussing organ- and site-selective prodrugs. Every company employing medicinal chemists will be interested in this practice-oriented overview of a key strategy in modern drug discovery and development.

A New Avenue of Research Beyond Traditional Studies of Vitamin E In the current literature, more than 95% of all studies of vitamin E are directed toward the specific exploration of the bioactive component a-tocopherol. Until recently, there has been a dearth of research into non-tocopherol vitamin E molecules. A unique resource that examines the n

Extensive experimentation and high failure rates are a well-recognized downside to the drug discovery process, with the resultant high levels of inefficiency and waste producing a negative environmental impact. Sustainable and Green Approaches in Medicinal Chemistry 2e reveals how medicinal chemistry can play a direct role in addressing this issue. After providing essential context to the growth of green chemistry in relation to drug discovery, the book goes on to identify a broad range of practical techniques and useful insights, revealing how medicinal chemistry techniques can be used to improve efficiency, mitigate failure and increase the environmental benignity of the entire drug discovery process. Drawing on the knowledge of a global team of experts, Sustainable and Green Approaches in Medicinal Chemistry, Second Edition encourages the growth of green medicinal chemistry, and supports medicinal chemists, drug discovery researchers, pharmacologists and all those in related fields across both academia and industry in integrating these approaches into their own work. This second volume of the second edition includes the development of nanoparticles and nanocomposites, as well as the application of ultrasound and microwave-induced methods; studies solventless synthesis; defines the role of steroids; studies reactions in aqueous solution; identifies enzyme-mediated reactions; investigates ionic liquids and deep eutectic solvents; explores natural products; investigates solid supports; realizes the effects of salts; focuses on combinatorial chemistry; develops one-pot methods; analyzes multi-component reactions; investigates dipole moment values; and examines computer-assisted methods. Highlights the need for adoption of sustainable and green chemistry pathways in drug development Reveals risk factors associated with the drug development process and the ways sustainable approaches can help address these Identifies novel and cost effective green medicinal chemistry approaches for improved efficiency and sustainability

This advanced text-cum-reference book presents a comprehensive account of the syntheses, reactions, properties and applications of all the most significant classes of heterocyclic compounds. This second volume in the series is an essential tool not only for advanced undergraduates and graduates, but also for academic and industrial researchers in organic, medicinal, pharmaceutical, dye and agricultural chemistry.

Key Heterocycle Cores for Designing Multitargeting Molecules provides a helpful overview of current developments in the field. Following a detailed introduction to the manipulation of heterocycle cores for the development of dual or multitargeting molecules, the book goes on to describe specific examples of such developments, focusing on compounds such as Benzimidazole, Acridine, Flavones, Thiazolidinedione and Oxazoline. Drawing on the latest developments in the field, this volume provides a valuable guide to current approaches in the design and development of molecules capable of acting on multiple targets. Adapting the heterocyclic core of a single-target molecule can facilitate its development into an agent capable of acting on multiple targets. Such multi-targeting drugs have the potential to become essential components in the design of novel, holistic treatment plans for complex diseases, making the design of such active agents an increasingly important area of research. Emphasizes the chemical development of heterocyclic nuclei, from single to multitargeting molecules Provides chapter-by-chapter coverage of the key heterocyclic compounds used in synthesizing multitargeting agents Outlines current trends and future developments in multitarget molecule design for the treatment of various diseases

Presents both the fundamental concepts and the most recent applications in solid-phase organic synthesis With its emphasis on basic concepts, Solid-Phase Organic Synthesis guides readers through all the steps needed to design and perform successful solid-phase organic syntheses. The authors focus on the fundamentals of heterogeneous supports in the synthesis of organic molecules, explaining the use of a solid material to facilitate organic synthesis. This comprehensive text not only presents the fundamentals, but also reviews the most recent research findings and applications, offering readers everything needed to conduct their own state-of-the-art science experiments. Featuring chapters written by leading researchers in the field, Solid-Phase Organic Synthesis is divided into two parts: Part One, Concepts and Strategies, discusses the linker groups used to attach the synthesis substrate to the solid support, colorimetric tests to identify the presence of functional groups, combinatorial synthesis, and diversity-oriented synthesis. Readers will discover how solid-phase synthesis is currently used to facilitate the discovery of new molecular functionality. The final chapter discusses how using a support can change or increase reaction selectivity. Part Two, Applications, presents examples of the solid-phase synthesis of various classes of organic molecules. Chapters explore general asymmetric synthesis on a support, strategies for heterocyclic synthesis, and synthesis of radioactive organic molecules, dyes, dendrimers, and oligosaccharides. Each chapter ends with a set of conclusions that underscore the key concepts and methods. References in each chapter enable readers to investigate any topic in greater depth. With its presentation of basic concepts as well as recent findings and applications, Solid-Phase Organic Synthesis is the ideal starting point for students and researchers in organic, medicinal, and combinatorial chemistry who want to take full advantage of current solid-phase synthesis techniques.