Discovery of new SCH 39166 analogs as potent and selective dopamine D-1 receptor antagonists

Department of Medicinal Chemistry, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
Bioorganic & medicinal chemistry letters (Impact Factor: 2.42). 02/2010; 20(3):836-40. DOI: 10.1016/j.bmcl.2009.12.100
Source: PubMed


A series of novel dopamine D(1) antagonists derived from functionalization of the D-ring of SCH 39166 were prepared. A number of these compounds displayed subnanomolar D(1) activity and more than 1000-fold selectivity over D(2). We found C-3 derivatization afforded compounds with superior overall profile in comparison to the C-2 and C-4 derivatization. A number of highly potent D(1) antagonists were discovered which have excellent selectivity over other dopamine receptors and improved PK profile compared to SCH 39166.

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Available from: Jing Su, Jul 02, 2015
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