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Design, synthesis, and evaluation of functionalized 5-(4-arylpiperazin-1-yl)-N-quinolinyl-pentanamides as selective dopamine D3 receptor ligands

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Abstract

Dopamine (1) plays a key role in normal physiological pathways in both the central nervous system and the periphery. The physiological impact of this neurotransmitter is mediated through its interaction with family of G-protein-coupled receptors (GPCRs). These receptors are designated as D1, D2, D3, D4, and D5 and divided into two sub-families, the D1-like sub-family (D1 and D5) and D2-like sub-family (D2, D3 and D4) based on pharmacological properties, amino acid homology, and genetic organization. Aberrant D3 activity has been linked to multiple diseases and conditions such as depression, schizophrenia, substance use disorder, inflammatory diseases, and Parkinson’s disease (PD). As part of our on-going program focused on the identification of novel D3 ligands, we have identified a novel series of 5-(4-arylpiperazin-1-yl)-N-quinolinyl-pentanamides that are high affinity ligands for this receptor.

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Acknowledgements

The research reported in this publication was supported by the National Institute on Drug Abuse (NIDA)/National Institutes of Health (NIH) under award number 2R01DA023957.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Temple University School of Pharmacy, 3307 North Broad Street, Philadelphia, PA, 194140, USA

    Benjamin E. Blass, Peng-Jen Chen & John C. Gordon

  2. Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Center, 3500 Camp Bowie Blvd., Fort Worth, TX, 76107, USA

    Michelle Taylor, Suzy A. Griffin & Robert R. Luedtke

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  1. Benjamin E. Blass
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Correspondence to Benjamin E. Blass.

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Blass, B.E., Chen, PJ., Taylor, M. et al. Design, synthesis, and evaluation of functionalized 5-(4-arylpiperazin-1-yl)-N-quinolinyl-pentanamides as selective dopamine D3 receptor ligands. Med Chem Res 31, 749–761 (2022). https://doi.org/10.1007/s00044-022-02873-3

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