During the last years it has been an increasing number of conferences and publications dealing with computer aided synthesis design (CASD). In the majority of these cases, the software uses a reaction database to extract examples that illustrate the synthesis routes suggested. However, there are not so many examples where the same principle is applied to generate new molecular entities, this is, applying reactions to a starting molecule and thus generating new molecules of interest (click here for a similar approach). The reasons for this fact can be of various nature, lack of a predefine target structure, huge number of potential reagents for a single reaction step, how many reaction steps are needed, etc… At Chemnotia, we do not have the answers to all possible question marks, but we found a way-around for most of the questions using ICFRP software. Focusing our attention on compound design in drug discovery, we found that it was possible to combine traditional drug design with reaction-based compound design methods to obtain the desired structures within the bioactive chemical space (Figure 1)
In the figure is shown how using chemnotia’s approach we could get analogues (represented as dark green dots) to those molecules of interest (biologically active and IP free) found using traditional drug design methods (light green dots). The molecules obtained with both methods (light and green dots) have the same predicted med chem properties, however the ICFRP molecules will include a synthesis path that will make it easier and faster to prepare them in the lab. In most cases, what it’s pursued with the traditional design methods is to validate a med chem hypothesis (based on previous active molecules, dockings, pharmacophore models, etc…), with chemnotia’s work-around your project will get answers faster.