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Reported biological activities of Stemona natural products, such as
antitussive activity, inspired the development of synthetic methods
to access several alkaloids within this family and in so doing develop
a general route to the core skeleta shared by the class of natural
products. The chemistry was subsequently adapted to afford a series
of analogue sets bearing simplified, diverse Stemona-inspired
skeleta. Over 100 of these analogues were subjected to general
G protein-coupled receptor profiling along with the known antitussive
compound, neostenine; this led to the identification of
hit compounds targeting several receptor types. The particularly
rich hit subset for sigma receptors was expanded with two focused
library sets, which resulted in the discovery of a fully synthetic,
potent chemotype of sigma ligands. This collaborative effort
combined the development of synthetic methods with extensive,
flexible screening resources and exemplifies the role of natural products
in bioactivity mining.

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ÑÌÔÆÌýÓê(½ð±Ò+10, ·­ÒëEPI+1): лл 2011-06-04 11:11:37
Reported biological activities of Stemona natural products, such asantitussive activity, inspired the development of synthetic methodsto access several alkaloids within this family and in so doing developa general route to the core skeleta shared by the class of naturalproducts.

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The chemistry was subsequently adapted to afford a seriesof analogue sets bearing simplified, diverse Stemona-inspiredskeleta.

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Over 100 of these analogues were subjected to generalG protein-coupled receptor profiling along with the known antitussivecompound, neostenine; this led to the identification ofhit compounds targeting several receptor types.

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The particularlyrich hit subset for sigma receptors was expanded with two focusedlibrary sets, which resulted in the discovery of a fully synthetic,potent chemotype of sigma ligands.

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This collaborative effortcombined the development of synthetic methods with extensive,flexible screening resources and exemplifies the role of natural productsin bioactivity mining.

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