Synthesis and biological evaluation of a library containing potentially 1600 amides / esters. A strategy for rapid compound generation and screening

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