ABSTRACT
A novel scaffold system for the generation of diversity libraries has been designed which allows for rapid modification not only of functional groups, but their spatial arrangements as well. The biphenyl scaffold allows for display of three or four diverse functional groups in a wide variety of spatial arrangements depending on the substitution pattern selected. The libraries are generated by a combination of solution and solid-phase chemistries and are cleaved off the solid-support for screening.
Subject(s)
Biphenyl Compounds/chemistry , Drug Design , Biphenyl Compounds/chemical synthesis , Chromatography, High Pressure Liquid/methods , Magnetic Resonance SpectroscopyABSTRACT
A series of analogous arrays of small, non-peptidyl, non-oligomeric compounds were synthesized on polystyrene resin. With the aid of a functionally differentiated phenolic scaffold, the batch preparation of unique benzamide and urea resins was accomplished, which were further derivatized in modified 96-well plates. An efficient cleavage reaction of the phenyl benzoate link enabled the isolation of more than 600 phenolic compounds in milligram quantities that were suitable for direct biological screening. The technology described herein represents a facile, economical approach to non-peptidyl chemical diversity.
