A Novel Route to Isoquinoline[2,1-g][1,6]naphthyridine, Pyrazolo[5,1-a] isoquinoline and Pyridazino[4´,5´:3,4]pyrazolo[5,1-a]isoquinoline Derivatives With Evaluation of Antitumor Activities

• Published in: Zeitschrift für Naturforschung. B, A journal of chemical sciences Vol. 68; no. 8; pp. 895 - 904
• Main Authors: Hassaneen, Hamdi M., Wardkhan, Wagnat W., Mohammed, Yasmin Sh
• Format: Journal Article
• Language: English
• Published: Verlag der Zeitschrift für Naturforschung 01-08-2013
• Subjects: Antitumor Activity; Hydroxamoyl Chlorides; Isoquinoline-1-acetonitrile; Naphthyridines; Pyrazoloisoquinolines; Pyridazinopyrazoloisoquinolines
• ISSN: 0932-0776; 1865-7117
• DOI: 10.5560/znb.2013-3101

(E)-2-Chloro-3-(2-cyanovinyl)-9,10-dimethoxy-4-oxo-6,7-dihydro-4H-pyrido[2,1-a] isoquinoline- 1-carbonitrile (5) was obtained by treatment of the 2-chloro-3-formylpyrido[2,1-a]isoquinoline derivative 3 with 2-(triphenylphosphoranylidene)acetonitrile (4). Treatment of 5 with sodium azide afforded the corresponding azido compound 6 which could be reduced by sodium dithionite to compound 7. A novel isoquinolino[2,1-g][1,6]naphthyridine derivative 11 was obtained by the reaction of phenyl isothiocyanate with the phosphorane compound 8, which was prepared by the reaction of compound 6 with triphenylphosphine. Treatment of 5 with amines 12a-c and thiophenols 14a-c in refluxing ethanol afforded the corresponding substitution products 13a-c and 15a-c, respectively. Also, the reaction of 1 with a-oxo hydroxamoyl chlorides 16 was reinvestigated, and the synthesized pyrazoloisoquinolines 19a-f and pyridazinopyrazoloisoquinolines 20a, e were screened for their in vitro antitumor activities.