Lead compounds approaches

Toxicology Many companies are known to use gene expression profiling to assess the potential toxicity of lead compounds. This approach may require a database of reference compounds with known pharmacological and toxicological properties. Lead compounds can be compared to the database to predict compound-related or mechanism-related toxicity [5]. 

Abt M, Lim Y-B, Sacks J, Xie M, Young SS. A sequential approach for identifying lead compounds in large chemical databases. Stat Sci 2001 16 154-68. 

The last step is to optimize the lead compounds. The computational methods in combination with SAR information has proved to be a powerful approach to determine areas on the molecule to expand, contract, or modify. Analogs of the lead compound are ranked using one or all of the following methods 1) qualitative predictions using molecular mechanics... 

The discovery of this lead compound as a potent PDF inhibitor was a result of an integrated combinatorial and medicinal chemistry approach based on the proposed generic PDF inhibitor structure. This focused chemical library was designed by Chen et al. [79], and was prepared using solid-phase parallel synthesis in which 22 amines and 24 amino acids were used as building blocks, as outlined in Scheme 23. 

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