Piperazine-based CCR5 antagonists as HIV-1 inhibitors. I: 2(S)-methyl piperazine as a key pharmacophore element.

Abstract Optimization of the piperidino-piperazines 1 and 2 provided early leads 3 and 4 , which showed good activity in the CCR5–RANTES binding assay and in antiviral assays. A systematic study around these structures showed that the 2( S )-methyl piperazine is essential for CCR5 affinity, which is further enhanced by forming the 2,6-dimethyl benzamide of the piperidine.