Ligand Design In Medicinal Inorganic Chemistry

Increasing the potency of therapeutic compounds, while limiting side-effects, is a common goal in medicinal chemistry. Ligands that effectively bind metal ions and also include specific features to enhance targeting, reporting, and overall efficacy are driving innovation in areas of disease diagnosis and therapy. Ligand Design in Medicinal Inorganic Chemistry presents the state-of-the-art in ligand design for medicinal inorganic chemistry applications. Each individual chapter describes and explores the application of compounds that either target a disease site, or are activated by a disease-specific biological process. Ligand design is discussed in the following areas: Platinum, Ruthenium, and Gold-containing anticancer agents Emissive metal-based optical probes Metal-based antimalarial agents Metal overload disorders Modulation of metal-protein interactions in neurodegenerative diseases Photoactivatable metal complexes and their use in biology and medicine Radiodiagnostic agents and Magnetic Resonance Imaging (MRI) agents Carbohydrate-containing ligands and Schiff-base ligands in Medicinal Inorganic Chemistry Metalloprotein inhibitors Ligand Design in Medicinal Inorganic Chemistry provides graduate students, industrial chemists and academic researchers with a launching pad for new research in medicinal chemistry.

The design of ancillary ligands used to modify the structural and reactivity properties of metal complexes has evolved into a rapidly expanding sub-discipline in inorganic and organometallic chemistry. Ancillary ligand design has figured directly in the discovery of new bonding motifs and stoichiometric reactivity, as well as in the development of new catalytic protocols that have had widespread positive impact on chemical synthesis on benchtop and industrial scales. Ligand Design in Metal Chemistry presents a collection of cutting-edge contributions from leaders in the field of ligand design, encompassing a broad spectrum of ancillary ligand classes and reactivity applications. Topics covered include: Key concepts in ligand design Redox non-innocent ligands Ligands for selective alkene metathesis Ligands in cross-coupling Ligand design in polymerization Ligand design in modern lanthanide chemistry Cooperative metal-ligand reactivity P,N Ligands for enantioselective hydrogenation Spiro-cyclic ligands in asymmetric catalysis This book will be a valuable reference for academic researchers and industry practitioners working in the field of ligand design, as well as those who work in the many areas in which the impact of ancillary ligand design has proven significant, for example synthetic organic chemistry, catalysis, medicinal chemistry, polymer science and materials chemistry.

Most drugs bind to a clearly defined macromolecular target that is complementary in terms of structure and chemistry. This observation is the basic paradigm of structure-based ligand design. Although this method first emerged in the 1980s, it has already become a powerful tool for pharmaceutical research. Much has been learned, however, since the first attempts to discover drugs on the basis of available biochemical and structural data. Nowadays, structure-based ligand design is an established method for creating drugs with new structural features, for modifying binding activities and pharmacokinetic properties, and for elucidating binding modes and structure-activity relationships. This volume presents the underlying principles of the approach and highlights real-life applications such as the discovery of HIV-protease inhibitors. It shows that structure-based ligand design has many advantages over other more traditional approaches to designing new drugs, providing it is employed properly and with a thorough knowledge of the pitfalls to avoid. The straightforward presentation and extensive list of references to the original literature as well as numerous color figures illustrating structural relationships make this volume an indispensable tool for every scientist working in the area of drug discovery.

Working from basic chemical principles, Metals in Medicine presents a complete and methodical approach to the topic. Introductory chapters discuss important bonding concepts applicable to metallo-drugs and their biological targets, interactions that exist between the agents and substances in the biological milieu, basic pharmacokinetic and pharmacodynamic properties including transport and uptake of drugs by the cells, and methods for measuring efficacy and toxicity of agents. The steps from drug discovery to market place are also briefly outlined and discussed. These chapters lay the groundwork, in order that students can clearly understand how agents work, whatever their subject background. Following this introduction, chapters focus on individual metallo-drugs and agents for treating and detecting disease, their synthesis, structure and general properties, known mechanism of action and important physical and chemical principles that apply. Topics covered include cisplatin; platinum anticancer drugs; ruthenium, titanium, and gallium for treating cancer; gold compounds for treating arthritis, cancer, and other diseases; vanadium, copper, and zinc in medicine; metal complexes for diagnosing disease; and metals in nanomedicine. Throughout the book, “Feature Boxes” expand on features of drugs that are not directly related to studying metals in medicine, for example discovery, medical use, specialist assays, and metals in biology. At the end of the chapters there are specifically designed problems/exercises that apply basic kinetic, thermodynamic and chemical principles to practical problem solving in metals in medicine. Metals in Medicine distils the essence of this important topic for undergraduate and graduate students in chemistry, biochemistry, biology and the related areas of biophysics, pharmacology, and bioengineering, and for researchers in other fields interested in getting a general insight into metals in medicine.

This first systematic summary of the impact of fragment-based approaches on the drug development process provides essential information that was previously unavailable. Adopting a practice-oriented approach, this represents a book by professionals for professionals, tailor-made for drug developers in the pharma and biotech sector who need to keep up-to-date on the latest technologies and strategies in pharmaceutical ligand design. The book is clearly divided into three sections on ligand design, spectroscopic techniques, and screening and drug discovery, backed by numerous case studies.

This book is organized into 12 important chapters that focus on the progress made by metal-based drugs as anticancer, antibacterial, antiviral, anti-inflammatory, and anti-neurodegenerative agents, as well as highlights the application areas of newly discovered metallodrugs. It can prove beneficial for researchers, investigators and scientists whose work involves inorganic and coordination chemistry, medical science, pharmacy, biotechnology and biomedical engineering.

This book reviews the current diagnostic and therapeutic uses of metal-containing compounds in medicine, as well as the role of metals in disease.

This insightful book represents the experience and understanding of the global experts in the field and spotlights both the structural and medicinal chemistry aspects of drug design. The need to 'encode' the physiological factors of pharmacology, a key area, is explored.