Potential Bioisostere Approaches

1) Molecular Operating Environment (MOE), Chemical Computing Group Inc., 1010 Sherbrooke St. West, Suite 910, Montreal, Quebec, Canada H3A 2R7. 

2) ROCS (Rapid Overlay of Chemical Structures), OpenEye Scientific Software, Santa Fe, NM, USA. 

The combination of these FieldPoints around the molecule effectively gives a calculated pharmacophore. This identifies not only the potential interactions for the molecule, but also an indication of the significance, by considering the contribution to the feature from the rest of the molecule. The Cresset-derived 

Negatively charged acceptor feature (cyan spheres) 

Of these three techniques considered. Cresset was selected for this experiment. This was so that the full interaction characteristics of the template molecule would be evaluated and compared to the potential bioisosteres in the library. The throughput of the approach is also such that a virtual library of up to 100 000compounds can be overlaid and scored against the template molecule, with the ability to perform an interactive visualization ofthe top-ranked hits from which to select molecules of interest. 

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