title: 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.
authors.affiliation: Department of Chemical Research, Schering-Plough Research Institute, 2015 Galloping Hill Road, K-15-2B-2800, Kenilworth, NJ 07033-1300, USA. jayaram@tagat@spcorp.com
authors.forename: J R
authors.initials: JR
authors.lastname: Tagat
authors.forename: S W
authors.initials: SW
authors.lastname: McCombie
authors.forename: R W
authors.initials: RW
authors.lastname: Steensma
authors.forename: S
authors.initials: S
authors.lastname: Lin
authors.forename: D V
authors.initials: DV
authors.lastname: Nazareno
authors.forename: B
authors.initials: B
authors.lastname: Baroudy
authors.forename: N
authors.initials: N
authors.lastname: Vantuno
authors.forename: S
authors.initials: S
authors.lastname: Xu
authors.forename: J
authors.initials: J
authors.lastname: Liu
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D065100:CCR5 Receptor Antagonists; D015497:HIV-1 / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D010879:Piperazines / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: C435643:2-methyl piperazine; D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D010879:Piperazines