By Donald J. Abraham (ed.)

This new quantity includes serious new chapters on Combinational Chemistry and a number of Parallel Synthesis, excessive Throughput Pharmacology, and Retrometabolism-Based Drug layout and focusing on.

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Extra resources for Burger's Medicinal Chemistry and Drug Discovery, Vol. 2: Drug Discovery and Drug Development

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Bauser, M. Betschinger, W. Kraas, and G. Jung, Bioorg. Med. Chem. , 8,1669 (1998). 94. E. Apletalina, J. Appel, N. S. A. Houghten, and I. Lindberg, J. Biol. , 273,26589 (1998). 95. J. S. Warmus, T. R. Ryder, J. C. Hodges, R. M. Kennedy, and K. D. Brady, Bioorg. Med. Chem. , 8,2309 (1998). 96. A. Bhandari, D. G. Jones, J. R. Schullek, K. Vo, C. A. , Bioorg. Med. Chem. , 8,2303 (1998). 97. S. Roychoudhury, S. E. Blondelle, S. M. Collins, M. C. Davis, H. D. McKeever, et d . , Mol. , 4, 173 (1998).

Resin tethered reagents used in combichem. More frequently automated chromatographic reverse phase methods are employed in which round the clock separations not requiring constant human supervision are available. Chromofiltration methods are powerful and rapid but often require study for optimization. We have found, for example, that choice of the appropriate solvent for solutionbased multiple parallel synthesis can occasionally result in reaction mixtures from which the desired product can be isolated in pure form by suitable choice of absorbent and concentration or evaporation from the eluent (139).

Microwave acceleration in combinatorial chemistry is a powerful technology for enhancing reactions on solid phases. The small molecule libraries just exemplified belong to the class called focused. That is, in each case a discrete molecular target was available at the outset and chemical routes were generally available. After some adaptation to the needs of the method and rehearsal of the chemistry, libraries could be generated relatively quickly. Many analogs were then available by comparatively simple variations in the reactants employed.

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