Studies directed toward the elucidation of the pharmacophore of steroid-based Sonic Hedgehog signaling inhibitors.
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ABSTRACT:
SUBMITTER: Isaacs AK
PROVIDER: S-EPMC3184309 | biostudies-literature | 2011 Oct
REPOSITORIES: biostudies-literature
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Studies directed toward the elucidation of the pharmacophore of steroid-based Sonic Hedgehog signaling inhibitors.
Isaacs André K AK Xiang Chaomei C Baubet Valérie V Dahmane Nadia N Winkler Jeffrey D JD
Organic letters 20110909 19
Previous work from our laboratory has established that the readily available steroid-based analog 2 of cyclopamine 1 is, like 1, a highly potent inhibitor of Hedgehog signaling. The first structure-activity relationship studies on 2, i.e., the synthesis and biological evaluation of both the C-17 epi analog 4 and the C-3 deoxy analog 11, both of which are more potent than cyclopamine 1, are described. The implications of these results for the emerging pharmacophore of these Sonic Hedgehog signali ...[more]
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