Literature DB >> 27080176

Synthesis and characterization of a series of chiral alkoxymethyl morpholine analogs as dopamine receptor 4 (D4R) antagonists.

Jonathan O Witt1, Andrea L McCollum1, Miguel A Hurtado2, Eric D Huseman1, Daniel E Jeffries1, Kayla J Temple1, Hyekyung C Plumley3, Anna L Blobaum3, Craig W Lindsley4, Corey R Hopkins5.   

Abstract

Herein, we report the synthesis and structure-activity relationship of a series of chiral alkoxymethyl morpholine analogs. Our efforts have culminated in the identification of (S)-2-(((6-chloropyridin-2-yl)oxy)methyl)-4-((6-fluoro-1H-indol-3-yl)methyl)morpholine as a novel potent and selective dopamine D4 receptor antagonist with selectivity against the other dopamine receptors tested (<10% inhibition at 1μM against D1, D2L, D2S, D3, and D5).
Copyright © 2016 Elsevier Ltd. All rights reserved.

Entities:  

Keywords:  Antagonist; Dopamine 4 receptor; Dopamine Selectivity; L-DOPA-induced dyskinesia; Morpholine

Mesh：

Substances：

Year:  2016        PMID： 27080176      PMCID： PMC5361409          DOI： 10.1016/j.bmcl.2016.03.102

Source DB:  PubMed          Journal:  Bioorg Med Chem Lett        ISSN： 0960-894X            Impact factor:   2.823


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