Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Two- and three dimensional combinatorial chemistry from multicomponent Grignard reagents.

Anne Bülow1, Steffen Sinning, Ove Wiborg

  • 1Department of Chemistry, University of Aarhus, Langelandsgade 140, DK-8000 Aarhus C, Denmark.

Journal of Combinatorial Chemistry
|July 13, 2004
PubMed
Summary

Researchers synthesized novel 3-substituted tropanes using Grignard reagents. Potent monoamine transporter ligands, including dopamine transporter (hDAT) inhibitors, were identified and synthesized from these compound libraries.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Feeling worse, feeling more overprotected: An experience sampling study among adolescents.

Child development·2026
Same author

Agomelatine normalizes region-specific, diurnal mGluR5 dysregulation in a chronic mild stress rat model of depression.

Progress in neuro-psychopharmacology & biological psychiatry·2025
Same author

Tuning artificial oxidase catalysis by cavity modification.

Organic & biomolecular chemistry·2025
Same author

Comparison of microglial cell population expansion in the <i>Tg344-AD</i> rat and <i>APP<sub>SWE</sub>/PS1<sub>ΔE9</sub></i> mouse model of Alzheimer's disease.

Journal of Alzheimer's disease reports·2025
Same author

Synthesis of an N-Galactosyl Norbornane Aziridine and its Potent Mixed Inhibition of Aspergillus oryzae β-Galactosidase.

Chembiochem : a European journal of chemical biology·2025
Same author

New partially silylated cyclodextrins with complex hydrogen bond networks.

Carbohydrate research·2025

Area of Science:

  • Medicinal Chemistry
  • Organic Synthesis
  • Neuroscience

Background:

  • Tropane alkaloids are a significant class of natural products with diverse pharmacological activities.
  • Monoamine transporters, particularly the dopamine transporter (DAT), are crucial targets for treating neurological and psychiatric disorders.
  • Developing novel ligands for monoamine transporters is essential for understanding their function and for drug discovery.

Purpose of the Study:

  • To synthesize and evaluate novel 3-substituted tropane derivatives as potential monoamine transporter ligands.
  • To explore the structure-activity relationships of tropane analogues targeting monoamine transporters.
  • To identify potent inhibitors of the human dopamine transporter (hDAT).

Main Methods:

  • Conjugate addition of Grignard reagents to methyl ecgonidine to generate libraries of 3-substituted tropanes.

Related Experiment Videos

  • Systematic variation of Grignard reagents and nitrogen substituents to create 2D and 3D compound libraries.
  • Screening of synthesized compounds for inhibition of monoamine transporter binding and reuptake.
  • Chemical synthesis and characterization of lead compounds.

    • Main Results:

    • Identification of two potent monoamine transporter ligands from a 2D library, with one compound showing high affinity for hDAT (K(i) = 26 nM).
    • Discovery of several potent dopamine transporter inhibitors from a 3D library, including a highly effective hDAT inhibitor.
    • Demonstration that 3-alkyltropanes are generally poor inhibitors of monoamine transporters.
    • The most potent hDAT inhibitor identified was (1R,2S,3S,5S)-3-(3,4-dimethylphenyl)-8-pentyl-8-azabicyclo[3.2.1]octane-2-carboxylic acid methyl ester.

    Conclusions:

    • The conjugate addition strategy is effective for generating diverse libraries of 3-substituted tropanes.
    • Novel and potent inhibitors of the dopamine transporter (hDAT) were successfully synthesized and identified.
    • The study provides valuable insights into the structural requirements for potent monoamine transporter ligands based on the tropane scaffold.