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

Benjamin E. Blass, Peng Jen Chen, Michelle Taylor, Suzy A. Griffin, John C. Gordon, Robert R. Luedtke

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Substance use disorder remains a major, unmet medical need. Cocaine is one of the most commonly abused recreational drugs and in 2018, there were over 5.5 million cocaine users. There are no approved therapies for the treatment of cocaine use disorder, but the D3 dopamine receptor has been identified as a potential therapeutic target. Our initial lead compound (6) is a potent D3 ligand with a high level of selectivity for D3 over D2, but its solubility is low. We have identified a new series of functionalized 5-(4-arylpiperazin-1-yl)-N-arylpentanamides (7) that are potent D3 binders that have moderate to high selectivity for D3 over D2. Exemplary members of this series were also significantly more soluble than our initial lead compound (6). [Figure not available: see fulltext.]

Original languageEnglish
Pages (from-to)132-145
Number of pages14
JournalMedicinal Chemistry Research
Volume31
Issue number1
DOIs
StatePublished - Jan 2022

Keywords

  • Cocaine
  • D dopamine receptor
  • D dopamine receptor
  • Dopamine
  • Substance use disorder

Fingerprint

Dive into the research topics of 'Design, synthesis, and evaluation of functionalized 5-(4-arylpiperazin-1-yl)-N-arylpentanamides as selective dopamine D3 receptor ligands'. Together they form a unique fingerprint.

Cite this