Practical applications for the medicinal chemist

Summation of the average contributions of individual binding groups, including allowance for conformational, 

If the observed binding of a drug to its receptor turns out to be substantially stronger than that calculated from equation (21.9) it is reasonable to expect that the drug structure offers a good fit to the receptor in a reasonably low-energy conformation. The structure should therefore provide an excellent starting point for the development of even more bioactive compounds. 

The fit may be unsatisfactory because only part of the drug is interacting with the receptor. This situation applies particularly to large drag molecules (e.g. peptide hormones), for which selective pruning of unused parts of the structure may produce simpler compounds without loss of affinity  

FIGURE 21.16 Sialidase inhibitors 2-deoxy-2,3-didehydro-D-N-acetyl neuraminic acid 7 and its 4-guanidino analog 8. 

CHAPTER 21 The Role of Functional Groups in Drug-Receptor Interactions 

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Finally, application of a particular biofunctional molecule in agriculture and other bioindustries or health care and medicine is the practical goal of the research. Chemists will synthesize many analogs and derivatives, and biologists will evaluate their biological effects. If one can find a useful compound, it will be commercialized for practical application. For example, gibberellin A3 (1) is used in Japan to produce seedless grapes. 

The Tophss Tree is an enduring tool for the iterative optimization of a chemical series where it is not possible to synthesize aU close analogs (i.e., for all medicinal chemistry projects) Figure 8.2 illustrates the practical application of the method. The continued popularity of the Tophss Tree (although, in the authors view, the tool is shU underused by medicinal chemists) is perhaps explained by the simplicity and visual applicatiou of the approach. However, the method is without a strong mathematical framework, which limits its apphcabihty to more complex problems, such as multiparameter optimization (MPO). 

Today, a large body of work on microwave-assisted synthesis exists in the published and patent literature. Many review articles [8-20], several books [21-23], and information on the world-wide-web [24] already provide extensive coverage of the subject. The goal of the present book is to present carefully scrutinized, useful, and practical information for both beginners and advanced practitioners of microwave-assisted organic synthesis. Special emphasis is placed on concepts and chemical transformations that are of importance to medicinal chemists, and that have been reported in the most recent literature (2002-2004). The extensive literature survey is limited to reactions that have been performed using controlled microwave heating conditions, i.e., where dedicated microwave reactors for synthetic applications with adequate... 

Ultrasound-assisted soft digestion has been used for other practical purposes from which analytical chemists can derive new applications. One case in point is in medicine, where ultrasound has been used as an adjunctive therapeutic treatment for clot dissolution of pharmacological thrombolysis. The combination of externally applied low-frequency high-intensity US with fibrinolytic therapy resulted in more rapid and complete reperfusion than the application of US or administration of fibrinolytic agents alone [42]. 

Before these results were published, polymer physicists and chemists mainly investigated only two phase-states, amorphous and crystalline. At the present time, along with these two states, the third phase-state of condensed systems, i.e. the liquid crystalline state, became very important. Here the situation turned out to be the same as in the case of low molar mass liquid crystals. In spite of the fact that historically the low molar mass substances in liquid crystalline state had been known for about a century, the intensive study of their properties began only after they had found an important practical application owing to a sharp change in optical properties of liquid crystals in electromagnetic fields (for visual displays) and as sensitive temperature indicators (in medicine). 

There are, of course, many fine textbooks of statistics, as there are for medicinal chemistry and quantitative drug design, and these are referred to as appropriate for further reading. However, I feel that there isn t a book which gives a practical guide for chemists to the processes of data analysis. The emphasis here is on the application of the techniques, although a certain amount of theory is required in order to explain the methods. This is not intended to be a statistical textbook, indeed an elementary knowledge of statistics is assiuned of the reader, but is meant to be a statistical companion to the novice or casual user. 

Humans have used practical applications of chemistry for thousands of years. The discovery and use of folk medicines, the development of metallurgical techniques, and the use of natural dyes are simple examples. For most of history, humans were able to use simple chemicals or a complex mixture of chemicals without actually understanding the science behind them. Organic chemistry became a defined science (the chemistry of carbon compounds) in the nineteenth century, but organic compounds have been known and used for millennia. Plants have been milked, cut, boiled, and eaten for thousands of years as folk medicine remedies, particularly in Africa, China, India, and South America. Modern science has determined that many of these plants contain organic chemicals with effective medical uses, and indeed many of our modern medicines are simply purified components of these plants or derivatives of them made by chemists. 

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