Scaffold hopping
In medicinal chemistry, scaffold hopping describes a strategy for developing new active ingredients . The aim is to change the basic structure of a known active ingredient in such a way that new active ingredients are obtained with the same mechanism of action. Scaffold hopping can be understood as an extension of the "bioisosteric replacement": Not only are individual atoms or groups of the molecule replaced, but the central area. The substituent must have a similar three-dimensional structure and pharmacophoric effect. Computer-based virtual screening methods are often used for scaffold hopping.
Motivation for scaffold hopping
The change in the basic structure of an active ingredient can, for. B. be desirable for the following reasons:
- Structural classes with unfavorable properties should be replaced (e.g. side effects, toxicity);
- The binding affinity for the target protein should be improved;
- An existing patent protection should be "abandoned". This was e.g. B. the case for the active ingredient Vardenafil , which was protected by a different patent than Sildenafil .
Individual evidence
- ↑ a b Hans-Joachim Böhm, Alexander Flohr, Martin Stahl: Scaffold hopping in Drug Discovery Today: Technologies 1, 2, 2004. doi : 10.1016 / j.ddtec.2004.10.009
- ↑ Nathan Brown (Ed.): Scaffold Hopping in Medicinal Chemistry in Methods and Principles in Medicinal Chemistry Vol. 58, 2014
- ↑ a b c thieme-chemistry.com: Römpp online version
- ↑ Hongmao Sun, Gregory Tawa, Ander Wallqvist: Classification of scaffold-hopping appraches in Drug Discovery Today 17, 7/8, 2012. doi : 10.1016 / j.drudis.2011.10.024