Protocols for amide high-speed analoging. Preparation of novel, small molecule cathepsin D inhibitors

Procedures for solution phase parallel synthesis of new, small molecule cathepsin D inhibitors by the coupling of acyl chlorides, sulfonyl chlorides and carboxylic acids with nitrogen nucleophiles have been established using polymer-bound reagents to facilitate the chemistry and/or to efficiently scavenge the unreacted starting materials and reaction by-products. Silver(I) benzoate was used to facilitate the coupling of acyl chlorides with less reactive anilines. Compound 4 was identified as a sub-micromolar cathepsin D inhibitor (IC50=320 nM). (C) 1999 Elsevier Science Ltd. All rights reserved.