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

J R Tagat; S W McCombie; R W Steensma; S Lin; D V Nazareno; B Baroudy; N Vantuno; S Xu; J Liu

doi:10.1016/s0960-894x(01)00381-x

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

Bioorg Med Chem Lett. 2001 Aug 20;11(16):2143-6. doi: 10.1016/s0960-894x(01)00381-x.

Authors

J R Tagat¹, S W McCombie, R W Steensma, S Lin, D V Nazareno, B Baroudy, N Vantuno, S Xu, J Liu

Affiliation

¹ 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

PMID: 11514156
DOI: 10.1016/s0960-894x(01)00381-x

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-HIV Agents / chemical synthesis
Anti-HIV Agents / chemistry
Anti-HIV Agents / pharmacology*
CCR5 Receptor Antagonists*
HIV-1 / drug effects*
Microbial Sensitivity Tests
Piperazines / chemistry
Piperazines / pharmacology*
Structure-Activity Relationship

Substances

2-methyl piperazine
Anti-HIV Agents
CCR5 Receptor Antagonists
Piperazines