Bioisosteric replacement definition

CATS3D was not only successful in scaffold hopping on the basis of the definition above (Meqi). We also observed a substructure hopping , which might be seen as an equivalent to more traditional bioisosteric replacement strategies. It seems that the CATS descriptor family represents molecules in a way that allows a combination of scaffold hopping and substructure hopping at once. This can result in a selection of molecules which would not be considered similar by other methods such as the MACCS keys. 

With regard to metabolic stability bioisosteric replacements, that is, substituents that are interchangeable with minimal effect on metabolism, one could look at the most neutral transformations, that is, the ones that did not result in a favorable or unfavorable effect on metabolic stability, at least within the defined tolerance threshold of 25%. The substituents of these transformations are therefore, by definition, isosteres. The 12 most neutral transformations in terms of the percentage of examples that led to no significant change are listed in Table 6.4. 

Some non-classical isosteres are reported in Table 15.5 and from a brief glance it can be noticed that they do not obey the steric and electronic definition of classical isosteres. A second notable characteristic of non-classical bioisosteres is that they do not have the same number of atoms as the substituent or moiety for which they are used as a replacement. 

---