A Solution‐Phase Screening Procedure for the Isolation of Active Compounds from a Library of Molecules

Abstract

Accelerated drug searches should be possible through the generation and screening of libraries of smaller organic molecules. The reaction of tetracarboxylic acid tetrachloride 1 with a mixture of 21 amines (predominantly amino acids) in solution yields a complex mixture, which can theoretically contain 97461 compounds. Compound 2, an inhibitor of trypsin-catalyzed amide hydrolysis (K1 = (9 ± 2) × 10−6M), was selected by four-step screening procedure. This result demonstrates the usefulness of libraries of molecules and the screening of these complex mixtures.