Substituted 4,6-diaminoquinolines as inhibitors of C5a receptor binding

J Med Chem. 1992 Jan 24;35(2):252-8. doi: 10.1021/jm00080a008.


The anaphylatoxin C5a is implicated in a number of inflammatory diseases. It is a highly cationic protein with 13 of 74 amino acids being either arginine or lysine. A search focusing on positively charged molecules, particularly amine-containing functionalities, led to the discovery of substituted 4,6-diaminoquinolines 1 [N,N'-bis(4-amino-2-methyl-6-quinolyl)urea] and 7 [6-N-(2-chlorocinnamoyl)-4,6-diamino-2-methylquinoline] as inhibitors of C5a receptor binding. These two compounds inhibited the binding of radiolabeled C5a to its receptor isolated from human neutrophils with IC50's = 3.3 and 12 micrograms/mL, respectively. Our efforts to enhance their potencies by chemical modification revealed a narrow profile of potency for effective C5a receptor binding inhibition.

MeSH terms

  • Aminoquinolines / chemical synthesis
  • Aminoquinolines / pharmacology*
  • Cell Degranulation / drug effects
  • Cell Degranulation / immunology
  • Complement C5a / antagonists & inhibitors
  • Complement C5a / metabolism*
  • Humans
  • In Vitro Techniques
  • Leukotriene B4 / metabolism
  • N-Formylmethionine Leucyl-Phenylalanine / metabolism
  • Neutrophils / drug effects
  • Receptor, Anaphylatoxin C5a
  • Receptors, Complement / antagonists & inhibitors*
  • Structure-Activity Relationship


  • Aminoquinolines
  • Receptor, Anaphylatoxin C5a
  • Receptors, Complement
  • Leukotriene B4
  • N-Formylmethionine Leucyl-Phenylalanine
  • Complement C5a