Interferon inducing activities of derivatives of 1,3-dimethyl-4-(3-dimethylaminopropylamino)-1H-pyrazolo[3,4-b]quinoline and related compounds

• Published in: Journal of medicinal chemistry 1976-02, Vol.19 (2), p.262-275
• Main Authors: Crenshaw, R. R, Luke, George M, Siminoff, Paul
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Female; Injections, Intraperitoneal; Interferon Inducers - chemical synthesis; Interferons - blood; Mice; Pyrazoles - administration & dosage; Pyrazoles - chemical synthesis; Pyrazoles - pharmacology; Quinolines - administration & dosage; Quinolines - chemical synthesis; Quinolines - pharmacology; Structure-Activity Relationship; Tilorone - pharmacology; Viral Plaque Assay
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00224a013

Syntheses and interferon inducing acitivites are reported for 137 relatives of 1,3-dimethyl-4-(3-dimethylamino-propylamino)-1H-pyrazolo[3,4-b]quinoline (1). Three different generalized synthetic schemes for the preparation of pyrazolo[3,4-b]quinolines are presented and limitations contrasted. Other heterocyclic nuclei containing the 3-dimethylaminopropylamino side chain include pyridine, quinoline, acridine, pyrazolo[3,4-b]pyridine, pyrazolo[3,4-B][1,8]naphthyridine, pyrazolo[4',3':5,6]pyrido[2,3-d]pyrimidine, dipyrazolo[3,4-b:4',3'-e]pyridine, pyrrolo-[2,3-b]quinoline, isothiazolo[5,4-b]quinoline, and pyrido[2,3-h]pyrazolo[3,4-b]quinoline. Structural requirements for interferon induction in this series are discussed and two of the more active compounds (172 and 196) are compared directly with tilorone.