Preface

This fourth volume of Frontiers in Medicinal Chemistry is an online compendium of 29 of the most influential publications in the journals Current Medicinal Chemistry, Current Pharmaceutical Design, and Current Topics in Medicinal Chemistry during the year 2005. All of the authors have had the chance to update their original manuscripts to reflect more recent development in their fields, and most have availed themselves of that opportunity. The challenge that all of us face in modern drug discovery and medicinal chemistry is to beat the odds: to maintain and even increase productivity in the face of scientific, financial and regulatory challenges.

Frontiers in Medicinal Chemistry, Vol. 4 is organized into eight sections. The first three sections cover general topics of strategy and mechanism, and the last five involve specific therapeutic categories. The first set of general sections includes General Principles and Strategies, Natural Products Research and Enzyme Inhibitors. The introductory article by J. Bajorath is a comprehensive and general review of computations approaches to medicinal chemistry by the use of ligand-based virtual screening. Other topics in the first and second sections include consideration of metal chelators in drug discovery and the evaluation and relevance of specific classes of natural products, a resurgent area of research. The third section on Enzyme Inhibitors is a collection of three manuscripts which could themselves have been put into specific therapeutic categories, but have been clustered together here because they target kinases, phosphatases and matrix metalloproteinases, protein families with broad reach across multiple therapeutic areas.

The final five sections cover the specific therapeutic categories of Anti- Infectives, Oncology, Vascular Research, Inflammation Research and Central Nervous System Disorders. The infectious diseases reviewed are Helicobacter pylori, HIV and tuberculosis. The Oncology section has an article on vaccine design by Lazoura et al. followed by three standard mechanism-based topics. The Vascular entries include the lipid-lowering approach for the prevention of heart attacks and stroke and nitric oxide donors for sickle cell disease. The Inflammation section reviews historical anti-inflammatory approaches and asthma in particular. Topics highlighted in the Central Nervous System section include two reviews on the prevalent and devastating neurological disorder of Alzheimer's disease. Also covered in this section are neuronal nitric oxide inhibitors, and the medicinal chemistry of the endo-cannabinoid system with applications in various fields including the management of pain.

Medicinal Chemistry is a vibrant and exciting field of study as represented by the contributions in this current volume. Our discipline is continuing to grow and evolve such as with the newer concepts of fragment-based drug discovery and ligand efficiency. We have the privilege to collaborate with pharmacologists, biochemists, process chemists, patent attorneys, toxicologists and eventually clinicians, all with the common goal to discover and introduce into therapy new molecular entities to treat patients with unmet medical needs.