Modification of agonist binding moiety in hybrid derivative 5/7-{[2-(4-aryl-piperazin-1-yl)-ethyl]-propyl-amino}-5,6,7,8-tetrahydro-naphthalen-1-ol/-2-amino versions: Impact on functional activity and selectivity for dopamine D2/D3 receptors
作者： Bhaskar Gopishetty , Suhong Zhang , Prashant S. Kharkar , Tamara Antonio , Maarten Reith
DOI: 10.1016/J.BMC.2013.03.059
关键词: Partial agonist 、 Chemistry 、 Imidazole 、 Agonist 、 Structure–activity relationship 、 Amide 、 Moiety 、 Stereochemistry 、 Radioligand 、 Radioligand Assay 、 Organic chemistry 、 Clinical biochemistry 、 Molecular medicine 、 Biochemistry 、 Molecular biology 、 Drug discovery 、 Pharmaceutical Science
摘要: The goal of the present study was to explore, in our previously developed hybrid template, effect introduction additional heterocyclic rings (mimicking catechol hydroxyl groups as bioisosteric replacement) on selectivity and affinity for D3 versus D2 receptor. In addition, we wanted explore derivatization functional agonist binding moiety compounds by us earlier from template. Binding (K(i)) new measured with tritiated spiperone radioligand HEK-293 cells expressing either or receptors. Functional activity selected assessed GTPγS assay. imidazole series, compound 10a exhibited highest whereas indole derivative 13 similar high affinity. Functionalization amino group (+)-9d different sulfonamides derivatives improved significantly (+)-14f exhibiting However, functionalization 15 (+)-9d, known partial agonist, sulfonate ester amide general modulated both cases loss potency resulted such derivatization.
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