Antagonists of the human CCR5 receptor as anti-HIV-1 agents. Part 2: structure-activity relationships for substituted 2-Aryl-1-[N-(methyl)-N-(phenylsulfonyl)amino]-4-(piperidin-1-yl)butanes

Bioorg Med Chem Lett. 2001 Jan 22;11(2):265-70. doi: 10.1016/s0960-894x(00)00639-9.

Abstract

(2S)-2-(3,4-Dichlorophenyl)-1-[N-(methyl)-N-(phenylsulfonyl)amino]-4-[spiro(2,3-dihydrobenzthiophene-3,4'-piperidin-1'-yl)]butane S-oxide (3) has been identified as a potent CCR5 antagonist lead structure having an IC50 = 35 nM. Herein, we describe the structure-activity relationship studies directed toward the requirement for and optimization of the C-2 phenyl fragment. The phenyl was found to be important for CCR5 antagonism and substitution was limited to small moieties at the 3-position (13 and 16: X= H, 3-F, 3-Cl, 3-Me).

MeSH terms

  • Animals
  • Anti-HIV Agents / chemical synthesis*
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / metabolism
  • Butanes / chemical synthesis
  • Butanes / chemistry
  • Butanes / metabolism
  • Butylamines / chemical synthesis
  • Butylamines / chemistry
  • Butylamines / metabolism
  • CCR5 Receptor Antagonists*
  • CHO Cells
  • Chemokine CCL4
  • Combinatorial Chemistry Techniques
  • Cricetinae
  • Humans
  • Inhibitory Concentration 50
  • Macrophage Inflammatory Proteins / metabolism
  • Piperidines / chemical synthesis
  • Piperidines / chemistry
  • Piperidines / metabolism
  • Protein Binding
  • Receptors, CCR5 / genetics
  • Receptors, CCR5 / metabolism
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis
  • Sulfonamides / chemistry
  • Sulfonamides / metabolism
  • Transfection

Substances

  • Anti-HIV Agents
  • Butanes
  • Butylamines
  • CCR5 Receptor Antagonists
  • Chemokine CCL4
  • Macrophage Inflammatory Proteins
  • Piperidines
  • Receptors, CCR5
  • Sulfonamides