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Australian Journal of Chemistry Australian Journal of Chemistry Society
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RESEARCH ARTICLE

X-Ray Crystallographic Structures of Biologically Active Trishomocubanes of the Types Pentacyclo[5.4.0.02,6.03,10.05,9]undecylamines and 4-Azahexacyclo[5.4.1.02,6.03,10.05,9.08,11]dodecane

Trevor W. Hambley, Robert Knott, Michael Kassiou and MacDonald J. Christie

Australian Journal of Chemistry 53(12) 899 - 904
Published: 2000

Abstract

The structures of three trishomocubanes of types pentacyclo[5.4.0.0 2,6 .0 3,10 .0 5,9 ]undecylamines and 4-azahexacyclo[5.4.1.0 2,6 .0 3,10 .0 5,9 .0 8,11 ]dodecanes have been determined. These ligands have demonstrated high selectivity and affinity for the sigma binding site, a molecular binding site important in the study of neurological disorders. The three compounds reported are members of an extensive series of ligands under investigation in a search for more efficacious pharmaceuticals. Compound (3) crystallized in the monoclinic space group C2/c with a 15.821(8), b 22.407(10), c 11.032(6) Å, β 115.15(3)°, V 3540(3) Å 3 , Z 8, and was refined to an R value of 0.054 on 1161F. Compound (4) crystallized in the triclinic, space group P1, a 11.278(3), b 13.139(2), c 7.444(2) Å, α 104.54(1), β 107.85(2), γ 68.51(1)°, V 964.9(4) Å 3 , Z 2, and was refined to an R value of 0.061 on 1939F. Compound (6) crystallized in the monoclinic space group P2 1 /c, a 9.971(4), b 11.989(4), c 12.993(5) Å, β 108.68(3)°, V 1471(1) Å3 , Z 4, and was refined to an R value of 0.060 on 1303F. The results are in accord with the hypothesis that the spatial relationship between the amine group and the hydrophobic regions of the molecule are important determinants of binding at the sigma site.

Keywords: Crystal structure; cubanes; neuroactivity; pharmaceuticals; sigma binding site.

https://doi.org/10.1071/CH00115

© CSIRO 2000

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