Modern Tools for the Synthesis of Complex Bioactive Molecules

Recent progress in high-throughput screening, combinatorial chemistry and molecular biology has radically changed the approach to drug discovery in the pharmaceutical industry. New challenges in synthesis result in new analytical methods. At present, typically 100,000 to one million molecules have to be tested within a short period and, therefore, highly effective screening methods are necessary for today's researchers – preparing and characterizing one compound after another belongs to the past. Intelligent, computer-based search agents are needed and «virtual screening» provides solutions to many problems. Such screening comprises innovative computational techniques designed to turn raw data into valuable chemical information and to assist in extracting the relevant molecular features. This handbook is unique in bringing together the various efforts in the field of virtual screening to provide the necessary methodological framework for more effective research. Leading experts give a thorough introduction to the state of the art along with a critical assessment of both successful applications and drawbacks. The information collated here will be indispensable for experienced scientists, as well as novices, working in medicinal chemistry and related disciplines.

Following Contemporary Drug Synthesis and The Art of Drug Synthesis (Wiley, 2004 and 2007), two well-received works, is this new book that demystifies the process of modern drug discovery for practitioners and students. An enhanced introduction covers areas such as background, pharmacology, SAR, PK/PD, efficacy, and safety. Focusing on the advantages of process synthesis versus the discovery synthetic route, Modern Drug Synthesis features authoritative coverage by distinguished editors and authors (some chapter authors are the actual inventor of the drug) of twenty different drug molecules.

The Handbook is a compilation of 99 articles on diverse reagents and catalysts that describe the synthesis of heteroarenes, the building blocks of a wide range of chemicals used in pharma and chemical industries. Articles are selected from the e-EROS database and edited to make sure that it includes only the material relevant to the topic of the book and focus on the synthetic aspects. This makes the articles very focused on the needs of readers wanting information on specific syntheses of specific heteroarenes. In addition, the chemistry of each ?parent heteroarene? is also included to ensure that the reader rapidly finds important information. The Handbook is a part of the Handbook of Reagents for Organic Chemistry series, aiming at collecting articles on a particular theme that individual researchers in academia or industry can use on a daily basis.

Drug design is a complex, challenging and innovative research area. Structure-based molecular design has transformed the drug discovery approach in modern medicine. Traditionally, focus has been placed on computational, structural or synthetic methods only in isolation. This one-of-akind guide integrates all three skill sets for a complete picture of contemporary structure-based design. This practical approach provides the tools to develop a high-affinity ligand with drug-like properties for a given drug target for which a high-resolution structure exists. The authors use numerous examples of recently developed drugs to present «best practice» methods in structurebased drug design with both newcomers and practicing researchers in mind. By way of a carefully balanced mix of theoretical background and case studies from medicinal chemistry applications, readers will quickly and efficiently master the basic skills of successful drug design. This book is aimed at new and active medicinal chemists, biochemists, pharmacologists, natural product chemists and those working in drug discovery in the pharmaceutical industry. It is highly recommended as a desk reference to guide students in medicinal and chemical sciences as well as to aid researchers engaged in drug design today.

The Art of Drug Synthesis illustrates how chemistry, biology, pharmacokinetics, and a host of other disciplines come together to produce successful medicines. The authors have compiled a collection of 21 representative categories of drugs, from which they have selected as examples many of the best-selling drugs on the market today. An introduction to each drug is provided, as well as background to the biology, pharmacology, pharmacokinetics, and drug metabolism, followed by a detailed account of the drug synthesis. Edited by prominent scientists working in drug discovery for Pfizer Meets the needs of a growing community of researchers in pharmaceutical R&D Provides a useful guide for practicing pharmaceutical scientists as well as a text for medicinal chemistry students An excellent follow-up to the very successful first book by these editors, Contemporary Drug Synthesis, but with all new therapeutic categories and drugs discussed.

Over the last three decades the importance of organosilicon chemistry has greatly increased because it has opened a number of new synthetic strategies. Silicon reagents are usually low-cost, versatile and allow a wide range of reactions. This is the first Handbook to compile essential Silicon containing reagents and makes use of the leading reagent database e-EROS. Another hot volume in the series Handbooks of Reagents for Organic Synthesis, this is a must-have resource for all synthetic chemists working in drug development and medicinal chemistry. For the selection the Editor focussed on three key synthetic approaches with the greatest impact: 1. Use of silicon as a 'temporary tether' by unifying a reactive pair of functional groups and taking advantage of their template-biased intramolecular cyclization. 2. The specific use of the silane functionality as a hetero t-butyl group, often colloquially referred to as the use of silicon as a 'fat proton'. 3. The use of the Brook rearrangement as an 'anion relay stratagem'. A new feature in this Handbook is the reagent finder, an alphabetically organized lookup table arranged by organic functionality and specific structure of the silicon atom to which it is bound.

Spurred by the desire to make chemistry a sustainable and «greener» technology, the field of organocatalysis has grown to become one of the most important areas in synthetic organic chemistry. Organic catalysts can often replace potentially toxic metal catalysts and allow reactions to proceed under mild reaction conditions, thereby saving energy costs and rendering chemical processes inherently safer. More importantly perhaps, organocatalysis offers a complementary reactivity in many instances leading to increased versatility. This Handbook describes 126 key reagents for organocatalytic reactions and will be especially useful for professionals in the area of sustainable chemistry, medicinal research, as well as synthetic organic chemists working in academia and the pharmaceutical industry. All the information compiled in this volume is also available in electronic format on Wiley Online Library. The 126 reagents represented here are but a small fraction of the ca. 5,000 reagents available in the electronic Encyclopedia of Reagents for Organic Synthesis (e-EROS). e-EROS offers various search interfaces to locate reagents of interest, including chemical structure, substructure and reactions search modes. e-EROS is updated regularly with new and updated entries.

Heteroarenes are among the most prevalent structural units in natural products, pharmaceuticals, agrochemicals, and other compounds of scientific or commercial interest. In the last decade, a broad range of novel synthetic methods has been developed to not only facilitate construction of the heteroarene motif, but to enable its modification through direct C?H functionalization. This Handbook describes 117 key reagents for selective heteroarene functionalization reactions, including both traditional and transition metal-catalyzed C?H functionalization. Since these reactions typically involve one heteroarene, a coupling partner and a catalyst, the handbook not only focuses on the catalyst itself but also contains other key reaction species. All the information compiled in this volume is also available in electronic format on Wiley Online Library. The 117 reagents represented here are but a small fraction of the ca. 5,000 reagents available in the electronic Encyclopedia of Reagents for Organic Synthesis (e-EROS). e-EROS offers various search interfaces to locate reagents of interest, including chemical structure, substructure and reactions search modes. e-EROS is updated regularly with new and updated entries.

One approach to organic synthesis is retrosynthetic analysis. With this approach chemists start with the structures of their target molecules and progressively cut bonds to create simpler molecules. Reversing this process gives a synthetic route to the target molecule from simpler starting materials. This “disconnection” approach to synthesis is now a fundamental part of every organic synthesis course. Workbook for Organic Synthesis: The Disconnection Approach, 2nd Edition This workbook provides a comprehensive graded set of problems to illustrate and develop the themes of each of the chapters in the textbook Organic Synthesis: The Disconnection Approach, 2nd Edition. Each problem is followed by a fully explained solution and discussion. The examples extend the student’s experience of the types of molecules being synthesised by organic chemists, and the strategies they employ to control their syntheses. By working through these examples students will develop their skills in analysing synthetic challenges, and build a toolkit of strategies for planning new syntheses. Examples are drawn from pharmaceuticals, agrochemicals, natural products, pheromones, perfumery and flavouring compounds, dyestuffs, monomers, and intermediates used in more advanced synthetic work. Reasons for wishing to synthesise each compound are given. Together the workbook and textbook provide a complete course in retrosynthetic analysis. Organic Synthesis: The Disconnection Approach, 2nd Edition There are forty chapters in Organic Synthesis: The Disconnection Approach, 2nd Edition: those on the synthesis of given types of molecules alternate with strategy chapters in which the methods just learnt are placed in a wider context. The synthesis chapters cover many ways of making each type of molecule starting with simple aromatic and aliphatic compounds with one functional group and progressing to molecules with many functional groups. The strategy chapters cover questions of selectivity, protection, stereochemistry, and develop more advanced thinking via reagents specifically designed for difficult problems. In its second edition updated examples and techniques are included and illustrated additional material has been added to take the student to the level required by the sequel, Organic Synthesis: Strategy and Control. Several chapters contain extensive new material based on courses that the authors give to chemists in the pharmaceutical industry. Workbook for Organic Synthesis: The Disconnection Approach, 2nd edition, combined with the main textbook, provides a full course in retrosynthetic analysis for chemistry and biochemistry students, and a refresher course for organic chemists working in industry and academia.

This book bridges the gap between sophomore and advanced / graduate level organic chemistry courses, providing students with a necessary background to begin research in either an industry or academic environment. • Covers key concepts that include retrosynthesis, conformational analysis, and functional group transformations as well as presents the latest developments in organometallic chemistry and C–C bond formation • Uses a concise and easy-to-read style, with many illustrated examples • Updates material, examples, and references from the first edition • Adds coverage of organocatalysts and organometallic reagents