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

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. (C) 2001 Elsevier Science Ltd. All rights reserved.