کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1357960 981306 2015 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Transformation of naltrexone into mesembrane and investigation of the binding properties of its intermediate derivatives to opioid receptors
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Transformation of naltrexone into mesembrane and investigation of the binding properties of its intermediate derivatives to opioid receptors
چکیده انگلیسی

We transformed naltrexone (5) with the morphinan skeleton into mesembrane (4) belonging to the Sceletium alkaloids via key intermediate 6, characterized by a cis-fused hydroindole skeleton with a suspended phenyl ring fixed by an epoxy bridge. We then investigated the binding affinities of 4 and the key intermediate 6 derivatives to the opioid receptors. Among the tested compounds, 15′, with a cis-fused hydroindole core, bound to the three opioid receptor types with strong to moderate affinities. The observed differences of binding affinities among the tested compounds were reasonably explained by the conformational analyses of the compounds. The structure–activity relationship (SAR) of the tested compounds like 15′ with the hydroindole structure was completely different from the reported SAR of morphinan derivatives with the hydroisoquinoline skeleton. Compound 15′ with a structure that differs from the morphinans represents a useful fundamental skeleton with a novel chemotype that may contribute to the development of new opioid ligands.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 23, Issue 3, 1 February 2015, Pages 439–448
نویسندگان
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