Synthesis of cyclopentadienyltricarbonyl rhenium phenyltropanes by double ligand transfer: organometallic ligands for the dopamine transporter.
Cyclopentadienyltricarbonyl rhenium (CpRe(CO)(3)) systems can be prepared from ferrocenes and perrhenate by a double ligand transfer (DLT) reaction that gives reasonable yields and shows excellent functional group tolerance. We used this reaction for the direct preparation of CpRe(CO)(3)-phenyltropane conjugates. Such agents, when labeled with technetium-99m, might function as imaging agents for the dopamine transporter (DAT) system that would be useful for assessing the onset and severity of Parkinson's disease. Of the CpRe(CO)(3)-tropane conjugates prepared by the DLT reaction (as well as other analogues prepared by related methods), those substituted at the N-8 position seem most promising; their affinity for the DAT in all cases was high, and their ferrocene precursors for the DLT reaction can be prepared in a convenient manner. By contrast, the 3 beta-conjugates were poor DAT binders. The modular nature of these systems offers considerable flexibility that could be used to improve the binding characteristics of these compounds further.
Cesati
Richard R
RR
Department of Chemistry, University of Illinois, 600 South Mathews Avenue, Urbana, Illinois 61801, USA.
Tamagnan
Gilles
G
Baldwin
Ronald M
RM
Zoghbi
Sami S
SS
Innis
Robert B
RB
Kula
Nora S
NS
Baldessarini
Ross J
RJ
Katzenellenbogen
John A
JA
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002855:Chromatography, Thin Layer; D050483:Dopamine Plasma Membrane Transport Proteins; D007202:Indicators and Reagents; D007700:Kinetics; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000737:chemistry*; D051379:Mice; D017072:Neostriatum / Q000378:metabolism; D009419:Nerve Tissue Proteins; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D012211:Rhenium / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D014326:Tropanes / Q000138:chemical synthesis*
D050483:Dopamine Plasma Membrane Transport Proteins; D007202:Indicators and Reagents; D008024:Ligands; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009942:Organometallic Compounds; C493215:Slc6a3 protein, mouse; D014326:Tropanes; D012211:Rhenium