Identification of TNF-alpha inhibitors from a split-pool library based on a tyrosine-proline peptidomimetic scaffold

The design and synthesis of a combinatorial library based on a 4-aryloxyproline scaffold with tyrosine as the aryl portion is described. The 1728 member library was prepared using the split-pool method to generate pools of compounds. Screening of the library components as mixtures followed by deconvolution led to the discovery of novel inhibitors of TNF-alpha induced apoptosis.