Spirodiketopiperazine-based CCR5 antagonists: Lead optimization from biologically active metabolite

Hydroxylated derivatives were designed and synthesized based on the information of oxidative metabolites. Compounds derived from beta-substituted (2R,3R)-2-amino-3-hydroxypropionic acid showed improved inhibitory activities against the binding of MIP-1 alpha to human CCR5, compared with the non-hydroxylated derivatives and the other isomers. (c) 2006 Elsevier Ltd. All rights reserved.