
TY  - JOUR
A1  - Liu, Xiang 
A1  - Kassiou, Michael 
A1  - Christie, MacDonald J. 
T1  - Synthesis and Binding Studies of Trishomocubanes: Novel Ligands for <emph type="2">&#963;</emph> Binding Sites
JF  - Australian Journal of Chemistry
JO  - Aust. J. Chem.
Y1  - 1999
VL  - 52
IS  - 7
SP  - 653
EP  - 656
KW  - 
UR  - https://doi.org/10.1071/CH99010 
N2  - Five new analogues of the &#963;2-selective trishomocubane N-(3&#8242;-fluorophenyl)methyl-4-azahexacyclo- &#91;5.4.1.0 2;6 .0 3;10 .0 5;9 .0 8;11 &#93;dodecan-3-ol (2) have been synthesized and assessed for their anities at both &#963;1 and &#963;2 sites. The structural requirements which influence &#963; binding of functionalized trishomocubanes were investigated with a view to develop more potent &#963; ligands, with particular emphasis on the &#963;2 subtype. All synthesized compounds displayed moderate anity to &#963; binding sites. Binding at the &#963;1 site ranged from 107 to 1100 n&#x041C; while binding at the &#963;2 site ranged from 135 to 250 n&#x041C;. The subtype selectivity was influenced by the nature and position of substitution on the aromatic ring. Fluorine substitution in the meta position, as in (2), is favoured over ortho, or para or meta and para difluoro substitution for &#963;2 selectivity. Compounds (3)&#8211;(5) not only demonstrated lower anity at the &#963;2 site but a reversal of subtype selectivity with preferential binding at the &#963;1 site (&#963;1/&#963;2: 0 . 8 for (3); 0 . 4 for (4); 0 . 8 for (6)). Introduction of CF3 and NO2 groups into the meta position in compounds (6) and (7) retained &#963;2 selectivity although to a lesser extent when compared to (2) (&#963;1/&#963;2: 7 . 6 for (2); 2 . 0 for (6); 4 . 5 for (7)). 
ER  -

