Highly Selective Dopamine D3 Receptor Antagonists with Arylated Diazaspiro Alkane Cores
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 (K i = 12–25.6 nM) and were highly selective for D3R vs D3R (ranging from 264- to 905-fold). Variation of...
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Veröffentlicht in: | Journal of medicinal chemistry 2017-12, Vol.60 (23), p.9905-9910 |
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container_title | Journal of medicinal chemistry |
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creator | Reilly, Sean W. Griffin, Suzy Taylor, Michelle Sahlholm, Kristoffer Weng, Chi-Chang Xu, Kuiying Jacome, Daniel A. Luedtke, Robert R. Mach, Robert H. |
description | 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 (K i = 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. |
doi_str_mv | 10.1021/acs.jmedchem.7b01248 |
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Med. Chem</addtitle><date>2017-12-14</date><risdate>2017</risdate><volume>60</volume><issue>23</issue><spage>9905</spage><epage>9910</epage><pages>9905-9910</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><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 (K i = 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.</abstract><pub>American Chemical Society</pub><pmid>29125762</pmid><doi>10.1021/acs.jmedchem.7b01248</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0002-7645-2869</orcidid><orcidid>https://orcid.org/0000-0002-1656-1895</orcidid><oa>free_for_read</oa></addata></record> |
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title | Highly Selective Dopamine D3 Receptor Antagonists with Arylated Diazaspiro Alkane Cores |
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