Privileged Structures - Dream or Reality: Preferential Organization of Azanaphthalene Scaffold

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.

Design, Synthesis and In Vitro Activity of Anticancer Styrylquinolines. The p53 Independent Mechanism of Action

“…The results were, however, unexpected and lead to some interesting remarks. The compounds that were used in this study were obtained during our search for active styrylquinolines as published recently [ 2 , 7 , 28 – 33 ]. As this experiment was concentrated on the styryl part of the molecule, we modified it according to the idea that is depicted in Fig 2 .…”

Chromone: A Valid Scaffold in Medicinal Chemistry

“…Many of these frameworks have been used as templates for the design of libraries of molecules for drug discovery [130][131][132][133][134] . In fact, the privileged structure concept has emerged as a successful approach for the drug discovery process, e.g.…”

“…In fact, the privileged structure concept has emerged as a successful approach for the drug discovery process, e.g. as core structures for synthesis and optimal starting points for the library design of ligands with affinity to certain molecular targets [130][131][132][133][134] . The last decade has brought more popularity to this idea and numerous scaffolds have been claimed to be privileged:…”

Making Sense of Structures by Utilizing Mother Nature's Chemical Libraries as Leads to Potential Drugs

“…Studying the azanaphthalene scaffolds from nature (e.g., quinolones and isoquinolines) one is struck by the number of bioactive compounds, both drugs and candidates as shown in the recent review by Polanski et al 4 Interestingly, this chapter does not discuss topological mimics of natural product structures such as ATP. Although bis-azanaphalene structures are discussed and some of the compounds currently under clinical trials as potential kinase inhibitors are shown, the concept of an NP-mimic is not addressed.…”