Artikel,
Scaffold hopping
Drug Discovery Today: Technologies, 1 (3): 217 - 224 (2004)
DOI: http://dx.doi.org/10.1016/j.ddtec.2004.10.009
Zusammenfassung
The aim of scaffold hopping is to discover structurally novel compounds starting from known active compounds by modifying the central core structure of the molecule. Scaffold hopping is a central task of modern medicinal chemistry requiring a multitude of techniques, which are discussed in this article. Their application has led to several molecules with chemically completely different core structures, and yet binding to the same receptor. Computational approaches for scaffold hopping highlight the challenges of the field that are still unsolved. Section Editor: Hugo Kubinyi – University of Heidelberg, Germany In lead optimization, systematic decoration of a common scaffold and bioisosteric replacement are the predominant techniques of structural variation. Scaffold hopping is an approach to generate new chemistry, starting from any lead structure. This article describes success stories as well as computational procedures to “hop” from one scaffold to another one, to modify affinities and selectivities, to improve physicochemical and \ADMET\ properties, and/or to arrive at patentable analogs.
