Abstract
A series of potent and selective D3 receptor (D3R) analogues with diazaspiro alkane cores were synthesized. Radioligand binding of compounds 11, 14, 15a, and 15c revealed favorable D3R affinity (Ki = 12-25.6 nM) and were highly selective for D3R vs D3R (ranging from 264- to 905-fold). Variation of these novel ligand architectures can be achieved using our previously reported 10-20 min benchtop C-N cross-coupling methodology, affording a broad range of arylated diazaspiro precursors.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Alkanes / chemistry
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Alkanes / pharmacology
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Animals
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Cell Line
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Dopamine Antagonists / chemistry*
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Dopamine Antagonists / pharmacology*
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Humans
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Ligands
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Piperazines / chemistry
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Piperazines / pharmacology
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Radioligand Assay
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Receptors, Dopamine D3 / antagonists & inhibitors*
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Receptors, Dopamine D3 / metabolism
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Spiro Compounds / chemistry
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Spiro Compounds / pharmacology
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Structure-Activity Relationship
Substances
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Alkanes
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Dopamine Antagonists
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Ligands
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Piperazines
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Receptors, Dopamine D3
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Spiro Compounds