Novel spirocyclic pyrrolidones as P2/P1 mimetics in potent inhibitors of HIV-1 protease

Bioorg Med Chem Lett. 2002 Dec 2;12(23):3431-3. doi: 10.1016/s0960-894x(02)00733-3.

Abstract

We have developed concise and efficient syntheses of novel spirocyclic pyrrolidones 1-3, which involve the alkylation of pyrrolidone precursor 13 with 1,5-dibromopentane, 16 and 15, followed by an in situ lactamization. Conjugates of 1 and 2 with P1'/P2' hydroxy-indanolamine moiety resulted in novel and potent inhibitors of HIV-1 protease 25 and 26, suggesting that 1 and 2 are novel P2/P1 HIV-PI mimetics.

MeSH terms

  • Alkylation
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology
  • Biomimetic Materials / chemistry
  • Biomimetic Materials / pharmacology
  • HIV Protease Inhibitors / chemistry*
  • HIV Protease Inhibitors / pharmacology*
  • Lactams / chemistry
  • Pyrrolidinones / chemistry*
  • Pyrrolidinones / pharmacology*
  • Spiro Compounds / chemistry
  • Spiro Compounds / pharmacology

Substances

  • Anti-HIV Agents
  • HIV Protease Inhibitors
  • Lactams
  • Pyrrolidinones
  • Spiro Compounds