Synthesis of dicationic diarylpyridines as nucleic-acid binding agents.
Synthesis of dicationic diarylpyridines as nucleic-acid binding agents.
复制标题
作为核酸结合剂的二芳基吡啶的合成。
DOI：
10.1016/0223-5234(96)88214-6
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发表时间：
1995
影响因子：
6.7
通讯作者：
Schinazi,Rf
中科院分区：
文献类型：
--
作者：
Kumar,A;Rhodes,Ra;Spychala,J;Wilson,Wd;Boykin,Dw;Tidwell,Rr;Dykstra,Cc;Hall,Je;Jones,Sk;Schinazi,Rf
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)phenylJpyridine 8 and 2,6-bis[3-(4,5-dihydro-1 H-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-1 H-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 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.
