Synthesis of dicationic diarylpyridines as nucleic-acid binding agents

Article abstract of DOI:10.1016/0223-5234(96)88214-6

The syntheses of 2,6-bis[4-(4,5-dihydro-1H-imidazol-2-yl)phenyl]pyridine 7, 2-[4-(4,5-dihydro-1H-imidazol-2-yl)-phenyl]-6-[3-(4,5-dihydro- 1H-imidazol-2-yl)phenyl]pyridine 8 and 2,6-bis[3-(4,5-dihydro-1H-imidazol-2-yl)phenyl]pyridine 9 in five steps from the appropriately substituted bromoacetophenone are described. 3,5-Bis[4-(4,5-dihydro-1H-imidazol-2-yl) phenyl]pyridine 13 is also reported, prepared in four steps from 4-bromophenylacetonitrile. The preparation of 2,5-bis[4-(4,5-dihydro-IH-imidazol-2-yl) phenyl]pyridine Is from 4-bromoacetophenone in six steps is presented. The dications bind to poly dA·dT in the order 7 > 13 > 18 > 8 > 9; the order of binding to poly A·U is 7 > 13 > 8 > 9; 18 essentially does not bind to the RNA model. Only 7 inhibits topoisomerase II at millimolar concentrations. The dicationic compounds that were tested against Pneumonocystis carinii in the immunosuppressed rat model show only modest activity and are moderately toxic. Some of the compounds demonstrated modest anti-HIV-1 activity and selectivity in primary lymphocytes.