Synthesis and affinity to DNA of phenylbenzoimidazoles and benzoimidazo[1,2-c]quinazolines

Abstract

Novel N-(benzoimidazophenyl)dialkylaminoalkylamides and 6-dialkylaminoalkylbenzoimidazo[1,2-c]quinazolines were prepared as potential interferon inducers and antiviral agents. They were screened for the DNA affinity by the ethidium bromide displacement assay. It was shown that the lg K(a) values of the compounds containing tetracyclic benzoimidazo[1,2-c]quinazoline fragment are approximately one order magnitude greater than those of the corresponding acyclic phenylbenzoimidazole derivatives.

Graphical abstract

Scheme 1

i: Cl(CH₂)_nCOCl, AcOH, AcONa, r.t.; ii: HNR₂, DMF, r.t., 24 h (n = 1); iii: HNR₂, EtOH, refl., 2 h (n = 2).

Scheme 2

i: Cl(CH₂)_nCOCl, AcOH, 60 °C; ii: HNR₂, DMF, r.t., 24 h (n = 1); iii: HNR₂, MeOH, refl. (n = 2).

Scheme 3

i: Pyridine-thionyl, CHCl₃, r.t.; ii: 6 M HCl, 80 °C.

Fig. 1

The affinity of the synthesized compounds to CT DNA.