Development of new protocols for the synthesis of arrays of heterocycles

Heterocyclic compounds, cyclic molecules in which one or more carbon atom is replaced by a heteroatom (commonly nitrogen, oxygen or sulfur) account for well over half of all known organic compounds. Many classes of natural products, as well as a large majority of commercially important drugs, agrochemicals, reprographic materials, dyes, etc., contain heterocyclic rings. Hence the synthesis and study of heterocyclic compounds, in particular nitrogen containing rings, is a subject of immense importance both for academia and industry. The commercial relevance of heterocyclic compounds is amply demonstrated by the list of best selling pharmaceuticals. In the 12 months to June 2005, seven of the top ten best sellers were nitrogen heterocycles with combined sales of $41 billion (out of $55.7 billion for the top ten). This proposal, which has the full support of GSK, seeks support to develop some new methods for the efficient and rapid laboratory preparation of arrays of heterocyclic molecules as potential medicines. Arrays are sets of compounds, usually prepared simultaneously by automated methods, where structural components of the molecule are varied systematically. Although array synthesis is a fundamental tool in modern medicinal chemistry, the reactions that can be used remain somewhat limited, and therefore new methods and protocols are urgently sought.