Synthesis and properties of bioactive 2- and 3-amino-8-methyl-8H-quino[4,3,2-kl]acridine and 8,13-dimethyl-8H-quino[4,3,2-kl]acridinium salts.
Cyclisation of 9-(benzotriazol-1-yl)acridine to the pentacycle 8H-quino[4,3,2-kl]acridine in a range of low-boiling solvents is mechanistically distinct from previously published photochemical (carbene) and thermolytic (radical) cyclisations. Fragmentation of the triazole ring of to a diazonium intermediate, and its subsequent heterolysis (-N(2)) and cyclisation is facilitated by solvation of intermediate zwitterionic species. Derivatives of 2- and 3-aminoquinoacridines methylated in the 8-position can be converted to 8,13-dimethylquino[4,3,2-kl]acridinium iodide salts with methyl iodide and were required for biological examination as potential telomerase inhibitors. The chloro group in 3-chloro-8-methyl-8H-quino[4,3,2-kl]acridine can be replaced efficiently by benzylamino, 4-morpholinyl and cyano substituents in palladium(0) mediated reactions.
Hutchinson
Ian
I
Cancer Research Laboratories, School of Pharmacy, University of Nottingham, Nottingham NG7 2RD, UK.
McCarroll
Andrew J
AJ
Heald
Robert A
RA
Stevens
Malcolm F G
MF
D000166:Acridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D045744:Cell Line, Tumor; D003500:Cyclization; D006358:Hot Temperature; D006801:Humans; D020128:Inhibitory Concentration 50; D012997:Solvents / Q000737:chemistry; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry
D000166:Acridines; D000970:Antineoplastic Agents; D012997:Solvents; D014230:Triazoles