SYNTHESIS OF DICATIONIC DIARYLPYRIDINES AS NUCLEIC-ACID BINDING-AGENTS

The syntheses of is[4-(4,5-dihydro-1H-imidazol-2-yl)phenyl]pyridine 7, hydro-1H-imidazol-2-yl)-phenyl]-6-[3-(4,5-dihydro- 1N-imidazol-2-yl)p henyl]pyridine 8 and 2,6-bis[3-(4,5-dihydro-1H-imidazol-2-yl) 9 in fiv e steps from the appropriately substituted bromoacetophenone are descr ibed. 3,5-Bis[4-(4,5-dihydro-1H-imidazol-2-yl) 13 is also reported, pr epared in four steps from 3-bromophenylacetonitrile. The preparation o f s[4-(4,5-dihydro-1H-imidazol-2-yl)-phenyl]pyridine 18 from 4-bromoac etophenone 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. On ly 7 inhibits topoisomerase II at millimolar concentrations. The dicat ionic compounds that were tested against Pneumonocystis carinii in the immunosuppressed rat model show only modest activity and are moderate ly toxic. Some of the compounds demonstrated modest anti-HTV-1 activit y and selectivity in primary lymphocytes.