Development of synthetic tools for the solid-phase synthesis of CNS active compounds (ACH.4597)

Combinatorial chemistry (CC) has recently become a major topic in organic synthesis as a result of its potential to develop into an essential tool for the discovery of new pharmaceuticals or catalysts. Despite greatly expanded research efforts in CC in the past three years, the development of new techniques for the synthesis of large numbers of compounds will also be vital in the near future. In this project we will address some of the current limiting factors in the use of solid phase procedures for CC such as

1. the relatively small amount of reaction types that has been applied on solid phase and
2. the limited choice of suitable linker molecules.

The researchgroup at the university of Amsterdam will focus at developing novel N-acyliminium ion chemistry on solid phase, so that new heterocyclic compound classes (with possible CNS activity) will become available via solid support reactions. In the group of the University of Nijmegen, the development of a novel 'thermocleavable linker' concept will be pursued, giving rise to stable linker molecules that upon detachment only leave a double bond in the molecule, instead of undesired polar functionalities. In a later stage of the project, once thermocleavable linkers have been developed, this protocol will be tested in combination with N-acyliminium ion chemistry to create libraries that will be tested for CNS activity. !--

Resultaten van het onderzoek