Tricyclic HIV integrase inhibitors: VI. SAR studies of 'benzyl flipped' C3-substituted pyrroloquinolines

Bioorg Med Chem Lett. 2009 Feb 15;19(4):1187-90. doi: 10.1016/j.bmcl.2008.12.079. Epub 2008 Dec 25.

Abstract

A series of C3 halobenzyl-substituted tricyclic HIV integrase inhibitors was prepared. Improvement in cell-based inhibitor potency was observed in comparison to previously disclosed tricyclic pyrroloquinolines carrying the 'halobenzyl tail' at the lactam nitrogen. Animal PK for several of the C3-substituted inhibitors was examined, with a dihaloaryl analog achieving good balance in protein-shifted EC(50) and t(1/2) in animal PK studies.

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-HIV Agents / chemical synthesis*
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology*
  • Dogs
  • Drug Design
  • HIV Integrase Inhibitors / chemical synthesis*
  • HIV Integrase Inhibitors / chemistry
  • HIV Integrase Inhibitors / pharmacology*
  • Humans
  • Molecular Structure
  • Pyrroles / chemical synthesis*
  • Pyrroles / chemistry
  • Pyrroles / pharmacology*
  • Quinolines / chemical synthesis*
  • Quinolines / chemistry
  • Quinolines / pharmacology*
  • Rats
  • Structure-Activity Relationship

Substances

  • Anti-HIV Agents
  • HIV Integrase Inhibitors
  • Pyrroles
  • Quinolines
  • pyrroloquinoline