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Highly Selective Dopamine D3 Receptor Antagonists with Arylated Diazaspiro Alkane Cores.

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.

SUBMITTER: Reilly SW

PROVIDER: S-EPMC5767125 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Highly Selective Dopamine D3 Receptor Antagonists with Arylated Diazaspiro Alkane Cores.

Reilly Sean W SW Griffin Suzy S Taylor Michelle M Sahlholm Kristoffer K Weng Chi-Chang CC Xu Kuiying K Jacome Daniel A DA Luedtke Robert R RR Mach Robert H RH

Journal of medicinal chemistry 20171121 23

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, affor ...[more]

PMID: 29125762

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