Synthesis and anti-HIV-1 activities of new pyrimido[5,4-b]indoles

Farmaco. 1999 Apr 30;54(4):255-64. doi: 10.1016/s0014-827x(99)00035-x.

Abstract

A set of new pyrimido[5,4-b]indole derivatives that are structurally related to some non-nucleside HIV-1 reverse transcriptase inhibitors were synthesized and biologically evaluated for their activity as inhibitors of wild and mutant HIV-1 RT types in an 'in vitro' recombinant HIV-1 RT screening assay, as well as anti-infectives in HLT4lacZ-1IIIB cells. Preliminary structure-activity relationships suggest that activity is promoted by simultaneous substitution in positions 2 and 4, especially when chains of alkyldiamine type are present, and by electron-releasing substituents (methoxy) in positions 7 and 8. The inactivity or the very low activity of title derivatives does not suggest interest in AIDS therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemical synthesis*
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology
  • Cell Line
  • Cell Survival / drug effects
  • Drug Evaluation, Preclinical
  • HIV-1 / drug effects*
  • Humans
  • Indoles / chemical synthesis*
  • Indoles / chemistry
  • Indoles / pharmacology
  • Reverse Transcriptase Inhibitors / chemical synthesis*
  • Reverse Transcriptase Inhibitors / chemistry
  • Reverse Transcriptase Inhibitors / pharmacology
  • Structure-Activity Relationship

Substances

  • Anti-HIV Agents
  • Indoles
  • Reverse Transcriptase Inhibitors