Download the full description of this project: ESR1: 3D Fragments with small aliphatic rings
At present, ‘flat’ heterocyclic aromatic compounds seem to be overrepresented in fragment libraries. It is being debated if more fragments with 3D character (mainly arising from sp3-‐ hybridised carbon atoms) should populate the fragment libraries, even though these have higher complexity (and therefore have a lower chance of binding to a target).
1. Develop of novel chemistries leading to fragments that contain small aliphatic rings.
2. The identification of 3D fragments that bind to protein targets. 3. The hit optimisation of selected hit fragments.
The aim is the development of focused libraries of small aliphatic rings, e.g., cyclobutyl-‐containing fragments. Towards this end, new chemistries with stereochemical control of the products will be developed. The resulting fragments have a higher complexity and their potential (e.g., hit rate and optimisation potential) will be explored by the Fragnet consortium. Fragment hits will be identified and used to fine-‐tune the focused libraries and to obtain optimized tool compounds for Fragnet projects.
Applicants must have experience with modern organic synthesis, including heterocyclic chemistry, parallel chemistry and air-‐sensitive reactions. In addition, candidates must have experience in purification and analyses (1D-‐NMR, 2D-‐NMR, LC-‐MS, HR-‐MS, IR) of organic compounds. An interest in medicinal chemistry and its biological context is also a requirement.
1. Wijtmans et al. MedChemComm. 2010, 1, 39-44.
2. de Kloe et al. Discov Today. 2009, 14, 630-46.