Title:Privileged Structures - Dream or Reality: Preferential Organization of Azanaphthalene Scaffold
VOLUME: 19 ISSUE: 13
Author(s):J. Polanski, A. Kurczyk, A. Bak and R. Musiol
Affiliation:Institute of Chemistry, University of Silesia, Szkolna 9, 40-006 Katowice, Poland.
Keywords:Azanaphthalene scaffold, chemical spaces, database mining, fragment-based design, privileged motifs
Abstract:The concept of privileged structures/substructures (PS) is the idea that certain structural features produce biological effects
more often than others. The PS method can be seen as an offspring of fragonomics, which is based on recent experimental measurements
of protein-ligand interactions. If PS prove to be true, then chemical motives that enrich biological activity can be used when designing
new drugs. However, PS remain controversial because we cannot be sure whether the excess of active structures does not result from an
abundance in chemical libraries. In this review, we will focus, in particular, on the preferential organization of azanaphthalene scaffolds
(AN) in drugs and natural products (NP), which are preferred by Nature in evolution. We will show that knowledge discovery in
molecular databases can reveal interesting time-trends profiles for important classes of potentially privileged scaffolds. The chemical
library of AN is dominated by monoaza-compounds, among which quinoline appears to be the most frequently investigated scaffold;
however; more sophisticated database mining seems to indicate different PS patterns within the AN scaffold family.
