Bioisosterism: Quantitation of structure and property effects

The powerful concept of bioisosterism is presented as a method for selecting molecular groups for drug design and lead-compound development. Three group-structure characteristics are described for this purpose. The E-State value for an attached atom is used as a measure of electrotopological group impact. The volume of the group is estimated from counts of sigma, pi, and lone-pair n electrons, as embodied in the valence and simple connectivity delta values for atoms in the group. Polarity is described in terms of the polarity index Q(v). Specific examples are given for commonly used groups. Parameter spaces encoding these three attributes are presented as examples that may be used to guide bioisostere selection in late-stage drug-design procedures. The method presented here is of practical value in the decision processes of molecular modification.