Structure-activity relationships of imidazo[4,5-f]quinoline partial structures and analogs. Discovery of pyrazolo[3,4-f]quinoline derivatives as potent immunostimulants

J Med Chem. 1992 Nov 27;35(24):4595-601. doi: 10.1021/jm00102a013.

Abstract

Structure-activity studies have been carried out on a series of imidazo[4,5-f]quinoline derivatives reported to have potent in vivo immunostimulatory activity. This activity has been confirmed, and subtle structure-activity relationships have been uncovered which resulted in the identification of novel analogs (pyrazolo[3,4-f]quinoline derivatives, 7a,b) with potent in vivo effects in a mouse protection model. Regioisomeric pyrazolo[4,3-f]quinoline derivatives (6a,b) were shown to be inactive. Data are presented which support the notion that the in vivo activity is mediated by an immunostimulatory mechanism.

Publication types

  • Comparative Study

MeSH terms

  • Adjuvants, Immunologic / chemical synthesis
  • Adjuvants, Immunologic / chemistry*
  • Adjuvants, Immunologic / therapeutic use
  • Aminoquinolines / chemical synthesis
  • Aminoquinolines / chemistry*
  • Aminoquinolines / pharmacology
  • Animals
  • Cattle
  • Drug Interactions
  • Escherichia coli Infections / drug therapy
  • Escherichia coli Infections / immunology
  • Female
  • Gentamicins / therapeutic use
  • Mice
  • Molecular Structure
  • Pyrazoles / chemical synthesis
  • Pyrazoles / chemistry*
  • Pyrazoles / pharmacology
  • Pyrazoles / therapeutic use
  • Quinolines / chemical synthesis
  • Quinolines / chemistry*
  • Quinolines / therapeutic use
  • Structure-Activity Relationship

Substances

  • Adjuvants, Immunologic
  • Aminoquinolines
  • Gentamicins
  • Pyrazoles
  • Quinolines
  • 9-((3-methoxyphenyl)amino)-7-methyl-1H-pyrazolo(3,4-f)quinoline