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

Abstract Hydroxylated derivatives were designed and synthesized based on the information of oxidative metabolites. Compounds derived from β-substituted (2 R ,3 R )-2-amino-3-hydroxypropionic acid showed improved inhibitory activities against the binding of MIP-1α to human CCR5, compared with the non-hydroxylated derivatives and the other isomers.