Synthesis and monoamine transporter affinity of 3-aryl substituted trop-2-enes

Aleksej Krunic; S V Santhana Mariappan; Marteen E A Reith; William J Dunn 3rd

doi:10.1016/j.bmcl.2005.08.082

Synthesis and monoamine transporter affinity of 3-aryl substituted trop-2-enes

Bioorg Med Chem Lett. 2005 Dec 15;15(24):5488-93. doi: 10.1016/j.bmcl.2005.08.082. Epub 2005 Oct 3.

Authors

Aleksej Krunic¹, S V Santhana Mariappan, Marteen E A Reith, William J Dunn 3rd

Affiliation

¹ Department of Biopharmaceutical Sciences, College of Pharmacy MC 865, University of Illinois at Chicago, 833 S. Wood Street, Rm 335, Chicago, IL 60612-7231, USA.

PMID: 16202585
DOI: 10.1016/j.bmcl.2005.08.082

Abstract

A series of new 3-aryl-tropanes have been synthesized, and their affinities and selectivities were evaluated for monoamine transporters. (1RS)-3-(Fluoren-2-yl)-8-methyl-8-azabicyclo[3.2.1]oct-2-ene exhibited the highest affinity for the human serotonin transporter (IC(50)=14.5nM). It is also 52-fold and 230-fold selective over human dopamine and norepinephrine transporters, respectively.

MeSH terms

Dopamine Plasma Membrane Transport Proteins / metabolism*
Humans
Kinetics
Ligands
Models, Molecular
Naphthols / chemical synthesis
Naphthols / pharmacokinetics
Norepinephrine Plasma Membrane Transport Proteins / metabolism*
Tropanes / chemical synthesis*
Tropanes / pharmacokinetics
Vesicular Monoamine Transport Proteins / metabolism*

Substances

Dopamine Plasma Membrane Transport Proteins
Ligands
Naphthols
Norepinephrine Plasma Membrane Transport Proteins
Tropanes
Vesicular Monoamine Transport Proteins