In the area of organic chemistry one major challenge we are currently faced with is how to assemble potentially useful molecules in new ways that generate molecular complexity and in sequences that are as efficient as possible. Our efforts in this regard, specifically for the preparation of amino containing compounds incorporating an aromatic ring, are described in this doctoral thesis. We discovered an interesting regioselectivity in an intramolecular Heck reaction, which we studied for a series of substrates that are unbiased in terms of the size of the newly formed ring, where very high levels of selectivity in relation to the new carbon-carbon bond are typically observed. DFT calculations were performed to attempt to shed light on the reaction sequence. This regioselective Heck reaction, combined with the reductive removal of the temporary amino-protecting group, allowed us to synthesize the Sceletium alkaloids: mesembrane, mesembranol and mesembrine.

Synthetic Methods in Drug Discovery Volume 1 focusses on the hugely important area of transition metal mediated methods used in industry. Current methods of importance such as the Suzuki-Miyaura coupling, Buchwald-Hartwig couplings and CH activation are discussed. In addition, exciting emerging areas such as decarboxylative coupling, and the uses of iron and nickel in coupling reactions are also covered. This book provides both academic and industrial perspectives on some key reactions giving the reader an excellent overview of the techniques used in modern synthesis. Reaction types are conveniently framed in the context of their value to industry and the challenges and limitations of methodologies are discussed with relevant illustrative examples. Edited and authored by leading scientists from both academia and industry, this book will be a valuable reference for all chemists involved in drug discovery as well as postgraduate students in medicinal chemistry.

Phosphatases, such as TNAP are fundamental in regulating the roles of cellular, and consequently numerous body functions. TNAP is a ubiquitous enzyme with a wide spectrum of substrates and specificity. Regulation at the cellular level and the lack of TNAP activity is a lethal condition. Recent findings of a highly specific regional, laminar and subcellular localization of TNAP in the cerebral cortex indicates that in addition to its metabolic and skeletal functions, TNAP also plays a role in regulating cerebral functions, most probably cognition. In fact, TNAP disturbance could result in complex diseases such as epilepsy, developmental retardation and Alzheimer's disease. Available data suggest that, regarding brain functions, TNAP is a potentially important target of clinical research. This book aims to provide an overview of our current understanding of the functions of TNAP in the brain and on other tissues and organs.

The authors of this guide are experts on the use of microwaves for drug synthesis as well as having much experience in teaching courses held under the auspices of the American Chemical Society and the IUPAC. In this handy source of information for any practicing synthetic chemist they focus on common reaction types in medicinal chemistry, including solid-phase and combinatorial methods. They consider the underlying theory, latest developments in microwave applications and include a variety of examples from recent literature, as well as less common applications that are equally relevant for organic and medicinal chemists. An indispensable reference for researchers with an affinity to modern methods.

This book offers deep insights into the thermodynamics and molecular structures of the twelve catalytically active isoforms of human carbonic anhydrase (CA) with a particular focus on inhibitor binding for drug design. X-ray crystallographic structures in combination with enzyme kinetic testing provide information on the interaction of CAs and their inhibitors, knowledge which is crucial for rational drug design. CAs are zinc carrying enzymes that catalyse the reversible interconversion of carbon dioxide and bicarbonate and are involved in numerous cellular processes. They are therefore a common target for drugs. The suppression of CA activities through inhibitory compounds has found application for example in diuretics and in glaucoma therapy. In this book methods used to determine binding thermodynamics of inhibitory compounds (Isothermal titration calorimetry, Fluorescent thermal shift assay/differential scanning fluorimetry and others) will be compared in detail. Also types and chemical synthesis of CA inhibitors, the use of antibodies against CAs as well as inhibitor application in animals are discussed.