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

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.