Synthesis and structure-activity relationships of a series of 4-methoxy-3-(piperidin-4-yl)oxy benzamides as novel inhibitors of the presynaptic choline transporter

Sean R. Bollinger, Darren W. Engers, Elizabeth A. Ennis, Jane Wright, Charles W. Locuson, Craig W. Lindsley, Randy D. Blakely, Corey R Hopkins

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The synthesis and SAR of 4-methoxy-3-(piperidin-4-yl) benzamides identified after a high-throughput screen of the MLPCN library is reported. SAR was explored around the 3-piperidine substituent as well as the amide functionality of the reported compounds. Starting from the initial lead compounds, 1-7, iterative medicinal chemistry efforts led to the identification of ML352 (10m). ML352 represents a potent and selective inhibitor of CHT based on a drug-like scaffold.

Original languageEnglish (US)
Pages (from-to)1757-1760
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume25
Issue number8
DOIs
StatePublished - Apr 15 2015
Externally publishedYes

Fingerprint

Benzamides
Lead compounds
Pharmaceutical Chemistry
Structure-Activity Relationship
Scaffolds
Amides
Libraries
Throughput
Pharmaceutical Preparations
piperidine
Lead
choline transporter

Keywords

  • Choline transporter
  • CHT
  • ML352
  • MLPCN
  • Structure-activity relationship

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

Synthesis and structure-activity relationships of a series of 4-methoxy-3-(piperidin-4-yl)oxy benzamides as novel inhibitors of the presynaptic choline transporter. / Bollinger, Sean R.; Engers, Darren W.; Ennis, Elizabeth A.; Wright, Jane; Locuson, Charles W.; Lindsley, Craig W.; Blakely, Randy D.; Hopkins, Corey R.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 25, No. 8, 15.04.2015, p. 1757-1760.

Research output: Contribution to journalArticle

Bollinger, Sean R. ; Engers, Darren W. ; Ennis, Elizabeth A. ; Wright, Jane ; Locuson, Charles W. ; Lindsley, Craig W. ; Blakely, Randy D. ; Hopkins, Corey R. / Synthesis and structure-activity relationships of a series of 4-methoxy-3-(piperidin-4-yl)oxy benzamides as novel inhibitors of the presynaptic choline transporter. In: Bioorganic and Medicinal Chemistry Letters. 2015 ; Vol. 25, No. 8. pp. 1757-1760.
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AU - Blakely, Randy D.

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