Lead optimization, drug design

Nowadays a broad range of methods is available in the field of chemoinfor-matics. These methods will have a growing impact on drug design. In particular, the discovery of new lead structures and their optimization will profit by virtual saeening [17, 66, 100-103]. The huge amounts of data produced by HTS and combinatorial chemistry enforce the use of database and data mining techniques. 

The previous sections have described methods to obtain 2-pyridone scaffolds. Both in the construction of new materials and especially in drug design and development, there is a desire to be able to derivatize and optimize the lead structures. In the following sections, some recent developments using MAOS to effectively substitute and derivatize 2-pyridone heterocycles are described. The reaction types described range from electrophilic-, and nucleophilic reactions to transition metal-catalyzed transformations (Fig. 7). To get an overview of how these systems behave, their characteristics imder conventional heating is first described in brevity. 

S. Sharma, Design of New Drugs for Helminth Diseases Lead Optimization in Benzimidazoles , in Advances in Drug Research , Eds. B. Testa, U. A. Meyer, Academic Press, London, 1994, Vol. 25, p. 103- 172. 

RACHEL (Real-time Automated Combinatorial Heuristic Enhancement of Lead compounds) is a lead optimization package [1] designed to optimize weak-binding lead compounds in an automated, combinatorial fashion. RACHEL incorporates numerous technological advances that enhance its ability to refine ligands. These technologies compensate for the difficulties inherent to computer-aided drug discovery, and they are discussed below in detail. 

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