title: Synthesis of dicationic diarylpyridines as nucleic-acid binding agents.
abstract: 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-1H-imidazol-2-yl)-phenyl]pyridine 18 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 immuno-suppressed 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.
authors.affiliation: Department of Chemistry, Georgia State University, Atlanta, GA 30303.
authors.forename: A
authors.initials: A
authors.lastname: Kumar
authors.forename: Ra
authors.initials: R
authors.lastname: Rhodes
authors.forename: J
authors.initials: J
authors.lastname: Spychala
authors.forename: Wd
authors.initials: W
authors.lastname: Wilson
authors.forename: Dw
authors.initials: D
authors.lastname: Boykin
authors.forename: Rr
authors.initials: R
authors.lastname: Tidwell
authors.forename: Cc
authors.initials: C
authors.lastname: Dykstra
authors.forename: Je
authors.initials: J
authors.lastname: Hall
authors.forename: Sk
authors.initials: S
authors.lastname: Jones
authors.forename: Rf
authors.initials: R
authors.lastname: Schinazi