دانلود کتاب Progress in Medicinal Chemistry, Vol. 36

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The six chapters presented in this volume review recent advances in important areas of medicinal chemistry. Chapter 1 describes the rational drug design of inhibitors of the influenza virus enzyme, sialidase, from which zanamivir was identified. This compound is representative of a new generation of agents for the treatment of human influenza infections. Nonpeptide small molecule fibrinogen antagonists are reviewed in chapter 2, indicating the extent of progress to identify compounds with good oral pharmacokinetics. The clinical trials of these potent antithrombotic agents are giving encouraging results in angioplasty and unstable angina and as an adjunct to thrombolysis therapy in myocardial infarction. Combinatorial chemistry, one of the most rapidly evolving techniques for drug discovery, is already the subject of many reviews but most are concerned with synthetic methodology. In contrast, chapter 3 considers the value of combinatorial chemistry to the medicinal chemist by reviewing the scope of its application to therapeutically important targets and reveals there is much progress to report. Advances in the molecular biology and pharmacology of the neurotransmitter, GABA, have established there is considerable heterogeneity in GABAa receptors, the receptors known to be modulated by all the clinically effective benzodiazepine anxiolytics. The consequent surge of activity to find anxiolytic agents which are more selective and possess fewer side-effects than the early benzodiazepines has led to the synthesis of a variety of novel structures. One such series of pyrido[1,2-a]benzimidazoles is described in chapter 4. There is good evidence to suggest that cyclooxygenase-2(COX-2) inhibitors will have important advantages over conventional non-steroidal anti-inflammatory drugs in arthritic disorders, and may be of value in Alzheimer's disease. The numerous compounds that exhibit COX-2 inhibitory activity are reviewed systematically in chapter 5. One of the most recent technologies to be developed is that of molecularly imprinted polymers. These materials have considerable potential in a variety of settings, including chromatographic separation of chiral molecules, and in the high throughput screening of complex mixtures such as combinatorial libraries. A survey of this field is given in chapter 6.