Lead optimization chemical arrays

Arrays of biological data can form the basis for uniquely informative molecular descriptors. By defining the relationships between compounds using biological descriptors (in vitro profiles) in addition to chemical structures, medicinal chemists are given new perspectives to support lead optimization. 

Papadatos, G., Cooper, A.W.J., Kadirkamanathan, V., Macdonald, S.J.E., McLay, I.M., Pickett, S.D., Pritchard, J.M., Willett, P and Gillet, V.J. (2009) Analysis of neighborhood behavior in lead optimization and array design. Journal of Chemical Information and Modeling,... 

USING CHEMOINFORMATICS TOOLS TO ANALYZE CHEMICAL ARRAYS IN LEAD OPTIMIZATION... 

A very important concept during lead optimization is that of the chemotype, also known as the chemical scaffold, core, framework, or template [34]. Chemotypes are the structural cores upon which different types of substituents can be attached. According to common lead optimization practice, chemists focus their work on a specific congeneric chemical series (or structural class), that is, a family of struaures which share the same chemotype or scaffold. The members of a chemical array are very likely to share the same core structure or chemotype. An algorithm was therefore developed to automatically and efficiently detect sets of compounds that share the same chemotype without any prior knowledge of a particular project. There is no universal definition of a chemotype however, some general observations are as follows ... 

Two pools of compounds form the input. The first pool contains molecules which were synthesized in chemical arrays and tested against a primary biochemical assay during a lead optimization project. The second pool is a superset of the first and contains all the compounds (both array members and singletons) that were ever tested against the same biochemical assay. 

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