Identification of TNF-α 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-α induced apoptosis. The identification of novel TNF-α inhibitors from a split-pool combinatorial library based on a 4-aryloxyproline scaffold is described.