Xx

Benzodiazepines anxiolytics, hypnotics, and compounds with activity at other targets. GYKI 52466 (glutamate receptor) (171) and inward-rectifying potassium channels (172). 13.2.2.2.2 1,4-Dihydropyridines. The DHP pharmacophore is a well-established chemical entity derived from the classic chemistry of Hantzsch (173).Nifedipine (Fig. 10.8) and several related DHPs, including arnlodipine, felo-dipine, nicardipine, nimodipine, and nisoldi-pine, are well-established antihypertensive...

References

B. Anderson in M. A. Wolff, Ed., Burger's Medicinal Chemistry, 5th ed., Vol. 1, John Wiley and Sons, New York, 1994, p. 901. 2. J. A Balfour and D. McTavish, Drugs, 46, 1025-1054 1993 . 3. P. Kleist, A. Ehrlich, Y. Suzuki, W. Timmer, N. Wetzelsberger, P. W. Liicker, and H. Fuder, Eur. J. Clin. Pharmacol., 53,149 1997 . 4. H. Ishida, S. Kato, M. Nishimura, N. Mizuno, S. Fujimoto, E. Mukai, M. Kajikawa, Y. Yamada, H. Odaka, H. Ikeda, and Y. Seino, Horm.Metab....

Lead Discovery Process

In contrast to the highly defined and strictly regulated process of drug development and manufacture, the initial discovery of drug candidates can be described as somewhat ad hoc and ill defined. Each pharmaceutical company, although agreeing on the ultimate goal, has developed a surprisingly wide array of technologies and approaches to achieve the same endpoint 15-21 . However, in this prototypical early discovery process, we can describe several distinct but overlapping activities that are...

Epitope Mapping

Site-directed mutagenesis technology has also been applied to one of the most challenging problems in structural biochemistry-the na-tureofthe protein-protein interaction. Whereas numerous examples of models of enzyme-li-gand complexes have been developed based on active-site modifications, the site-directed mutagenesis method is being extended to the formidable problem of defining the essential elements of a protein-protein e.g., a protein substrate to a protease or a hormone to its receptor...

History Of Lead Discovery And Screening

Serendipity has been the key to the pharmaceutical industry's success over many decades. The emergence of this accidental approach to drug discovery has its origins in early history with traditional natural herbal remedies that were passed from generation to generation in local communities or tribes. In fact, the early history of lead discovery is all about natural products and herbal remedies, the use of which dates back thousands of years. Ancient Chinese and Indian medicinal recipes, along...

Protein Engineering And Sitedirected Mutagenesis

Rapid developments in the technique of site-directed mutagenesis have created the ability to change essentially any amino acid, or even substitute or delete whole domains, in any protein, with the goal of designing and constructing new proteins with novel binding, clearance, or catalytic activities 31, 32 . The concomitant changes in protein folding and tertiary structure, protein physiology, binding affinities for a receptor or hormone , binding specificities either for substrate or receptor ,...

Ho Oh

Profile of different protected monosaccharides to determine the outcome 103 . The reactivity of a monosaccharide is highly dependent on the protecting groups and the anomeric-acti-vating group used. By adding substrates in sequence from most reactive to least reactive, the predominance of a desired target compound is assured. The key to this approach is to have extensive quantitative data regarding the relative reactivities of different protected monosac-charides. Thus, a reactivity database on...