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.
Tagat
J R
JR
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
McCombie
S W
SW
Steensma
R W
RW
Lin
S
S
Nazareno
D V
DV
Baroudy
B
B
Vantuno
N
N
Xu
S
S
Liu
J
J
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
C435643:2-methyl piperazine; D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D010879:Piperazines