A Novel Procedure for the Synthesis of Libraries Containing Small Organic 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.