SYNTHESIS AND BIOLOGICAL EVALUATION OF A LIBRARY CONTAINING POTENTIALLY 1600 AMIDES ESTERS - A STRATEGY FOR RAPID COMPOUND GENERATION AND SCREENING

A library of potentially 1600 amide/ester dimers was prepared by react ing 40 acid chlorides with 40 nucleophiles. The whole library was pres ented for biological screening in 80 sample mixtures, with each of the possible products appearing in a unique pair of samples. The potentia l of this strategy for rapid identification of chemical leads was demo nstrated by the discovery of (1) with micromolar affinity for the NK3 receptor and (2), a weak inhibitor of the matrix metalloprotease MMP-1 .