Solid-Phase Synthesis of Highly Substituted Peptoid 1(2H)-Istsquinolinones

摘要

The rapid synthesis of large organic compound collections by combinatorial methods on solid supports is a promising strategy for the discovery of new pharmaceutical leads. We have discovered trimeric N-substituted glycines (peptoids) with nanomolar binding affinities for the alpha-adsenergic and mu-opiate receptors from such combinatorial libraries. One focus of our drug discovery effort, is to increase the structural rigidity, complexity, and diversity of the libraries. This can be done by introducing new monomeric backbone units with greater functionality and by application of powerful solution phase organic reactions to the solid phase. In particular, we wanted to explore homogeneoas transition metalcatalyzed reactions. We wish to report here the solidphaae synthesis of highly substituted 1(2H)-isoquinolinones bearing peptoid side chains.