[Pyrrolo(2,3-c)quinolines and pyrrolo(3,4-d)quinolines--synthesis and investigation of lipoxygenase inhibition]

Pharmazie. 2002 Apr;57(4):243-9.
[Article in German]

Abstract

The Paal-Knorr synthesis of the cyclic hemiketonacetal 4 yields the pyrrole-2,4-dicarboxylic acid diesters 1c and 7 via the cyclic hemiaminals 5 and 6; while the pyrrole-2-carboxylic acid ester 9 is formed from the 1,4-diketon 10. Under reducing conditions 1c and their 4-carboxylic acid 8 give the pyrrolo[3,4-c]quinoline carboxylic acid ester 2a; the cyclic hydroxamic acid 11 and the lactam 12 of the pyrrolo[2,3-c]quinoline type are obtained from compound 9. The isomeric compounds of the pyrrolo[3,4-c]quinoline series 16, 17 and 18, respectively, are synthesized from the pyrroles 14 and 15; the cyclic hemiacetal 13 was used as educt. The tricyclic hydroxamic acids 16 and 17 weakly inhibit the 5-lipoxygenase (IC50 > 10 microM, relating to the formation of LTB4 of human whole blood).

Publication types

  • English Abstract
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arachidonate 5-Lipoxygenase / blood
  • Humans
  • Hydroxamic Acids / chemical synthesis
  • Hydroxamic Acids / pharmacology
  • In Vitro Techniques
  • Leukotriene B4 / metabolism
  • Lipoxygenase Inhibitors / chemical synthesis*
  • Lipoxygenase Inhibitors / pharmacology*
  • Neutrophils / drug effects
  • Neutrophils / enzymology
  • Pyrroles / chemical synthesis*
  • Pyrroles / chemistry
  • Pyrroles / pharmacology*
  • Quinolines / chemical synthesis*
  • Quinolines / chemistry
  • Quinolines / pharmacology*

Substances

  • Hydroxamic Acids
  • Lipoxygenase Inhibitors
  • Pyrroles
  • Quinolines
  • Leukotriene B4
  • Arachidonate 5-Lipoxygenase