Synthesis of dopamine transporter selective 3-[2-(diarylmethoxyethylidene)]-8-alkylaryl-8-azabicyclo[3.2.1]octanes.
A series of 3-[2-(diarylmethoxyethylidene)]-8-alkylaryl-8-azabicyclo[3.2.1]octanes was synthesized and the binding affinities of the compounds were determined at the dopamine and serotonin transporters. The 8-phenylpropyl analogues 8a (K(i)=4.1 nM) and 8b (K(i)=3.7 nM) were the most potent compounds of the series with binding affinities 3 times greater than GBR-12909. In addition, 8a (SERT/DAT=327) was over 300-fold more selective for the dopamine transporter than the serotonin transporter.
Bradley
Amy L
AL
Department of Chemistry, University of New Orleans, New Orleans, LA 70148, USA.
Izenwasser
Sari
S
Wade
Dean
D
Cararas
Shaine
S
Trudell
Mark L
ML
D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002421:Caudate Nucleus / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009419:Nerve Tissue Proteins; D009795:Octanes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats; D013329:Structure-Activity Relationship
D019086:Bridged Bicyclo Compounds, Heterocyclic; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009795:Octanes; C493216:Slc6a3 protein, rat