Structure-activity relationships of imidazo[4,5-f]quinoline partial structures and analogs. Discovery of pyrazolo[3,4-f]quinoline derivatives as potent immunostimulants.
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.
Moyer
M P
MP
Central Research Division, Pfizer Inc., Groton, Connecticut 06340.
Weber
F H
FH
Gross
J L
JL
D000276:Adjuvants, Immunologic / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D000634:Aminoquinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D004347:Drug Interactions; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000276:immunology; D005260:Female; D005839:Gentamicins / Q000627:therapeutic use; D051379:Mice; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D013329:Structure-Activity Relationship
D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D005839:Gentamicins; D011720:Pyrazoles; D011804:Quinolines; C078821:9-((3-methoxyphenyl)amino)-7-methyl-1H-pyrazolo(3,4-f)quinoline